Parental practices that influence children's development: how often are they implemented and by whom-results from the NASCITA birth cohort study.

This study aims to assess how commonly 15 parental practices, known to have positive effects on child and adult health, are carried out by families in Italy, if they are related, and which characteristics are associated with implementation. Children participating in the NASCITA Cohort, a prospective study in which family pediatricians in Italy collect data on children and their families, were included if they had sufficient data. Data on practice implementation, socio-demographic characteristics, and interrelatedness between practices were analyzed. In all, 3337 children were included. Their mothers had an average age at birth of 33 years (range 17-52) and medium-high levels of education (86% of mothers) and employment (72%). No smoking or alcohol in pregnancy, supine infant sleeping position, and tummy time were the most commonly implemented practices (by over 85% of mothers, each), while the least common was exclusive breastfeeding at 6 months (28%). Parental practices are related and several socio-demographic characteristics influence their implementation, with mother's educational level and geographic area of residence influencing most of the practices (each influencing 12 of 15 practices). Low educational level (OR 0.34; 95% CI 0.26-0.44), being born abroad (OR 0.43; 95% CI 0.34-0.56), and residing in the South (OR 0.49; 95% CI 0.41-0.58) most reduce the probability of implementing numerous supportive practices (all three P < 0.001).    Conclusion: Socio-demographic factors contribute significantly to carrying out supportive practices. Future interventions should address the identified inequalities, prioritizing families most in need. Direct involvement of pediatricians is warranted given their favorable position for promoting positive behaviors. What is Known: • Several parental actions in the early life of a child are known to have positive effects on later child health and development. • While folic acid supplementation and exclusive breastfeeding have been promoted for years, other supporting actions are less well-known. What is New: • Rates of parental adherence to the different supportive actions varied greatly and actions were often scantly adopted. • Socio-demographic characteristics influenced adherence, with young, unemployed mothers with low educational levels, living in the South, or who were born abroad adhering significantly less.

Pediatrician and parental evaluation of child neurodevelopment at 2 years of age.

BACKGROUND: The early identification of infants with a risk for neurodevelopmental disorders in the first few years of life is essential for better developmental outcomes. Screenings should be carried out by combining the family pediatricians' and parents' perspectives, the two fundamental sources of information on children's health. The present study has three aims: (a) to test the feasibility of parent-report instruments to detect warning signs in their children's development; (b) to ascertain whether there is an agreement between the family pediatricians' (FP) clinical judgments of warning signs and the parental perceptions; (c) to determine whether there is a link between parents' distress and child development. METHODS: Within the NASCITA birth cohort, in addition to the family pediatrician's clinical evaluation with routine tools, the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) was completed by parents to assess the child's language, social skills, behavior, and sensory areas. Parents were also asked to complete the Parenting Stress Index, Short Form (PSI-SF) to verify the magnitude of stress in the parent-child system. Univariate and multivariate analyses were performed to evaluate the association between child and parental characteristics and the presence of warning signs. RESULTS: The follow-up assessment was completed for 435 infants: 69 (15.8%) presented warning signs: 43 in the pediatrician's assessment and 36 in the M-CHAT-R (10 in both). A total of 16 children (14 with warning signs) received a diagnosis after a specialist evaluation. Being male (OR 2.46, 95%CI: 1.23-4.91) and having sleep disorders (OR 2.43, 95% CI 1.17-5.04) was associated with a greater likelihood of warning signs in the multivariate analysis, while reading aloud was a protective factor (not exposed versus exposed (OR = 3.14; 95% CI 1.60-6.17). For 73 children (18.4%), at least one parent tested positive for PSI-SF. An increased prevalence of parental distress was observed in children with warning signs (OR 2.36, 95% CI 1.27-4.37). CONCLUSIONS: Integrating physician and parental perspectives during well-child visits and in clinical practice appears feasible and can improve the identification of children at risk of developmental disorders.

Organizational Learning in Healthcare Contexts after COVID-19: A Study of 10 Intensive Care Units in Central and Northern Italy through Framework Analysis.

The rapid spread of the SARS-CoV-2 virus has forced healthcare organizations to change their organization, introducing new ways of working, relating, communicating, and managing to cope with the growing number of hospitalized patients. Starting from the analysis of the narratives of healthcare workers who served in the intensive care units of 10 hospitals in Central and Northern Italy, this contribution intends to highlight elements present during the pandemic period within the investigated structures, which are considered factors that can influence the birth of organizational learning. Specifically, the data collected through interviews and focus groups were analyzed using the framework analysis method of Ritchie and Spencer. The conducted study made it possible to identify and highlight factors related to aspects of communication, relationships, context, and organization that positively influenced the management of the health emergency, favoring the improvement of the structure. It is believed that the identification of these factors by healthcare organizations can represent a valuable opportunity to rethink themselves, thus becoming a source of learning.

National, longitudinal NASCITA birth cohort study: prevalence of overweight at 12 months of age in children born healthy.

OBJECTIVE: To estimate the prevalence of overweight at 12 months in an Italian birth cohort and to identify factors related to an increased likelihood of being overweight. METHODS: The Italian NASCITA birth cohort was analysed. Infants were classified as underweight (<5th), normal weight (5-84th) and overweight (≥85th centile) at 12 months of age according to the WHO percentiles of body mass index (BMI) and the prevalence of overweight was estimated. To test the association between the chance of being overweight and parental and newborn characteristics, and infant feeding, healthy newborns (no preterm/low birth weight and with no malformations), with appropriate-for-gestational-age birth weight were selected, and univariate and multivariate analyses were performed. RESULTS: The prevalence of overweight was 23.5% (95% CI 22.2% to 24.8%) in all cohort members with 12-month data (N=4270), and 23.1% in the appropriate-for-gestational age subsample (N=2835).A big infant appetite (OR 3.92, 95% CI 2.40 to 6.40) and living in southern Italy (OR 1.58, 95% CI 1.29 to 1.94) were the main variables associated with a greater likelihood of being overweight. Breastfeeding practice did not influence the chance of being overweight, but was associated with an increase (exclusive breast feeding for at least 6 months) or a decrease (breast feeding for at least 12 months) in BMI z score at 12 months. CONCLUSIONS: The sociodemographic factors (eg, area of residence, maternal employment status) seem to be the most relevant determinants influencing the chance of being overweight at 12 months. Early interventions, with particular attention to vulnerable families, may be helpful in preventing childhood and adult obesity.

National, longitudinal NASCITA birth cohort study to investigate the health of Italian children and potential influencing factors.

PURPOSE: The NASCITA Study, a national-level, population-based, prospective cohort study, was set up to better understand the early health status of Italian children, comprising their physical, cognitive and psychological development, and how it is affected by social and health determinants, including nurturing care. NASCITA will also assess geographical differences and disparities in healthcare. PARTICIPANTS: Participating family paediatricians from throughout Italy enrolled infants born during the enrolment period (April 2019-July 2020). The 5054 newborns seen by the 139 paediatricians for at least two visits, including the first well-child visit, and for whom parental consent was given, make up the baseline population. FINDINGS TO DATE: Mothers had a mean age at delivery of 33.0 years and tended to have a high or medium level of education (42.5% university and 41.7% high school degrees) and to be employed (69.7%). One-third (36.1%) took folic acid supplementation appropriately, and 6.5% smoked or consumed alcohol (10.0%) during pregnancy. One-third (31.7%) of deliveries were caesarean deliveries. Concerning the newborns, 5.8% had a low birth weight and 6.2% were born prematurely. The majority (87.7%) slept in the supine position, and 63.6% were exclusively breast fed at 1 month, with a decreasing north to south prevalence (χ2 t 52; p<0.001). Significant north-south differences were found in all areas, including parental education, behaviours in pregnancy and hospital practices. When compared with national level data, the cohort population's distribution, maternal sociodemographic characteristics and newborn physical characteristics reflect those of the Italian population. FUTURE PLANS: Data will continue to be collected during the well-child visits until the children are 6 years old, and multiple health outcomes will be studied, spanning child development and illness, as well as potentially related factors including caregiving routines. The findings will be used to develop specific interventions to improve children's health. TRIAL REGISTRATION NUMBER: NCT03894566.

European birth cohorts: a consideration of what they have addressed so far.

BACKGROUND: Knowing the research issues addressed by other cohorts when setting up new cohorts allows researchers to avoid unnecessary duplication of efforts, while permitting collaborations, including data merging data, to better tackle knowledge gaps. This study describes the topics addressed by European birth cohorts, the interaction between these cohort interests and aims, and describes the scientific publications deriving from the cohorts. METHODS: A previous study found 66 pregnancy and 45 birth cohorts in Europe. In this study, between August and October 2020, the predominant key areas addressed by the 45 birth cohorts identified in the previous study were evaluated, as were the publications found in PubMed that were associated with the 45 cohorts. A network analysis was performed to show the connections between the 13 key areas identified. A focus on a topic in common between two areas was provided, describing the related publications. RESULTS: A total of 1512 references were found in PubMed (148 publications per cohort). Thirteen predominant key areas were identified, the most common of which was "Environmental" (addressed by 20 cohorts). The Environmental, Genes, and Lifestyle exposure areas were the prevalent topics characterizing the network figure. The Environmental area had the largest number of interactions with the other areas, while the Prematurity area (4 cohorts) the least. The focus provided on smoking led to the comparison of 35 publications from the Environmental group of cohorts and 22 from the Prematurity group, but their objectives did not overlap. CONCLUSIONS: The results of this descriptive study show that the environment is a priority research area for cohorts in Europe and that cohorts with different research areas may have study issues in common, but may approach them from different viewpoints. Birth cohorts have wide-ranging aims and it would be almost impossible, and undesirable, to have perfectly overlapping and comparable objectives, but joining efforts would permit maximum use of available resources.

Intrauterine Exposures and Maternal Health Status during Pregnancy in Relation to Later Child Health: A Review of Pregnancy Cohort Studies in Europe.

We show a description of pregnancy cohorts in the European region. Our investigation identified 66 pregnancy cohorts, mostly hosted in Western Central Europe. Among these 66 cohorts, 24 began recruitment before the year 2000, while six cohorts are still enrolling. The most common topics were lifestyle, environment and nutrition with allergies and neurodevelopment being a minority. We observed a pattern of positive correlations between data collected using medical records, structured interviews, and the collection of biological samples. Objectively assessed data were negatively correlated with self-administered questionnaires. Eight cohorts addressed intrauterine exposure, focusing on environmental pollutants such as endocrine-disrupting chemicals. The effects of these compounds on the developing foetus have been studied greatly, but more research on their effects is still needed. Many cohorts investigated genetics through the collection of biological samples from the mothers and children, to improve knowledge on the mother-to-child transmission of genetic information, antibodies, microbiota, etc. Paediatric epidemiology represents an important field of research since preserving healthy lives from conception onwards is the most efficient way to improve population health. According to our report, it seems that this field of research is well developed in Europe, where numerous high profile studies are currently ongoing.

Informatics Methodology Used in the Web-Based Portal of the NASCITA Cohort Study: Development and Implementation Study.

BACKGROUND: Many diseases occurring in adults can be pinned down to early childhood and birth cohorts are the optimal means to study this connection. Birth cohorts have contributed to the understanding of many diseases and their risk factors. OBJECTIVE: To improve the knowledge of the health status of Italian children early on and how it is affected by social and health determinants, we set up a longitudinal, prospective, national-level, population-based birth cohort, the NASCITA study (NAscere e creSCere in ITAlia). The main aim of this cohort is to evaluate physical, cognitive, and psychological development; health status; and health resource use in the first 6 years of life in newborns, and potential associated factors. A web-based system was set up with the aim to host the cohort; provide ongoing information to pediatricians and to families; and facilitate accurate data input, monitoring, and analysis. This article describes the informatics methodology used to set up and maintain the NASCITA cohort with its web-based platform, and provides a general description of the data on children aged over 7 months. METHODS: Family pediatricians were contacted for participation in the cohort and enrolled newborns from April 2019 to July 2020 at their first well-child visit. Information collected included basic data that are part of those routinely collected by the family pediatricians, but also parental data, such as medical history, characteristics and lifestyle, and indoor and outdoor environment. A specific web portal for the NASCITA cohort study was developed and an electronic case report form for data input was created and tested. Interactive data charts, including growth curves, are being made available to pediatricians with their patients' data. Newsletters covering the current biomedical literature on child cohorts are periodically being put up for pediatricians, and, for parents, evidence-based information on common illnesses and problems in children. RESULTS: The entire cohort population consists of 5166 children, with 139 participating pediatricians, distributed throughout Italy. The number of children enrolled per pediatrician ranged from 1 to 100. The 5166 enrolled children represent 66.55% (5166/7763) of the children born in all of 2018 covered by the same pediatricians participating in the cohort. The number of children aged over 7 months at the time of these analyses, and for whom the most complete data were available upon initial analyses, was 4386 (2226/4381 males [50.81%] and 142/4370 twins [3.25%]). The age of the mothers at birth of the 4386 children ranged from 16 to 54 years. Most newborns' mothers (3758/4367, 86.05%) were born in Italy, followed by mothers born in Romania (101/4367, 2.31%), Albania (75/4367, 1.72%), and Morocco (60/4367, 1.37%). Concerning the newborns, 138/4386 (3.15%) were born with malformations and 352/4386 (8.03%) had a disease, most commonly neonatal respiratory distress syndrome (n=52), neonatal jaundice (n=46), and neonatal hypoglycemia (n=45). CONCLUSIONS: The NASCITA cohort is well underway and the population size will permit significant conclusions to be drawn. The key role of pediatricians in obtaining clinical data directly, along with the national-level representativity, will make the findings even more solid. In addition to promoting accurate data input, the multiple functions of the web portal, with its interactive platform, help maintain a solid relationship with the pediatricians and keep parents informed and interested in participating. TRIAL REGISTRATION: ClinicalTrials.gov NCT03894566; https://clinicaltrials.gov/ct2/show/NCT03894566.

An Inventory of European Birth Cohorts.

Many birth cohorts have been carried out. We performed a review of European birth cohorts to see the countries involved, provide a panorama of the current research topics and design, and, more generally, provide input for those creating collaborations and laying out guidelines aimed at unifying cohort methodologies to enable data merging and maximize knowledge acquisition. We searched PubMed and Embase for articles referring to longitudinal, prospective European birth cohorts and searched online cohort inventories. We found references to 111 birth cohorts, 45 of which began enrolment at birth. These cohorts began between 1921 and 2015 and represented 19 countries, with varying sample sizes (236 to 21,000 children). As of 5 January 2020, were still recruiting. The main areas addressed were allergic diseases (14 cohorts) and environmental exposure (f12 cohorts) and most cohorts were publicly funded. Given the large costs of running cohorts and the importance of long follow-up periods in identifying the risk factors for disorders thought to have a perinatal/early life etiology, current cohorts must be designed to answer research questions considering several aspects, from genetic ones to psychological, social, and environmental ones. Furthermore, universally recognized methodological aspects are needed to permit the comparison and merging of cohort data.

NASCITA Italian birth cohort study: a study protocol.

BACKGROUND: Young children's healthy development depends on nurturing care, which ensures health, nutrition, responsive caregiving, safety and security, and early learning. Infancy and childhood are characterized by rapid growth and development, and these two factors contribute largely to determining health status and well-being across the lifespan. Identification of modifiable risk factors and prognostic factors during the critical periods of life will contribute to the development of effective prevention and intervention strategies. The NASCITA (NAscere e creSCere in ITAlia) study was created to evaluate physical, cognitive, and psychological development, health status and health resource utilization during the first six years of life in a cohort of newborns, and to evaluate potential associated factors. METHODS: NASCITA is an ongoing, dynamic, prospective, population-based birth cohort study of an expected number of more than 5000 newborns who will be recruited in 22 national geographic clusters starting in 2019. It was designed to follow children from birth to school entry age for a wide range of determinants, disorders, and diseases. Recruitment of the newborns (and their parents) will take place during the first routine well-child visit, which takes place at the office of the pediatrician assigned to them by the local health unit of residence, and which is scheduled for all newborns born in Italy within the first 45 days of their life. Data will be web-based and collected by the family pediatricians during each of the 7 standard well-child visits scheduled for all children during their first 6 years of life. Information on every contact with the enrolled children in addition to these prescheduled visits will be also recorded. DISCUSSION: The NASCITA cohort study provides a framework in which children are followed from birth to six-years of age. NASCITA will broaden our understanding of the contribution of early-life factors to infant and child health and development. NASCITA provides opportunities to initiate new studies, also experimental ones, in parts of the cohort, and will contribute relevant information on determinants and health outcomes to policy and decision makers. Cohort details can be found on https://coortenascita.marionegri.it. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03894566. Ethics committee approval: 6 February 2019, Verbale N 59.

Globalization of pediatric research: pharmacological RCTs in Latin America.

Globalization caused a shift in trial locations towards low-middle income countries, raising ethical concerns. These include the risk that conditions primarily affecting children in these countries will be neglected in favor of those affecting developed countries. We analyzed 253 published and 69 ongoing pharmacological RCTs performed in Latin America between 2000 and 2015 involving exclusively children. While over 50% of the previously highly investigated diseases were no longer priorities, other diseases acquired greater attention in recent years. Brazil and Mexico resulted as the most active countries. A large gap remains between the real needs of children in these countries and scientific research.

An audit to evaluate an institute's lead researchers' knowledge of trial registries and to investigate adherence to data transparency issues in an Italian research institute registry.

BACKGROUND: Clinical trial registries have been a priority topic in the past few years in promoting data transparency and accountability. In this context, in 2011, the IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" set up a registry to collect data on all studies in which the institute's researchers are involved. In this study we present a self-audit in order to detect the lead researchers' general knowledge on registries, the completeness and quality of the randomized controlled trial (RCT) data inputted in an Italian research institute's registry, and the researchers' adherence to both registration requirements and the institute transparency goal, aiming to improve standards and leading to greater awareness of the issues involved. METHODS: A questionnaire-based audit was conducted. To interview researchers we included questions ranging from general knowledge on registries (e.g., what are the aims of registries?) to questions about their knowledge of the Mario Negri's registry, questions on selected trials and registration, included information on the protocol, and the results. RESULTS: The audit sample covers 12 of the 47 RCTs at the institute's Milan branch, representing all the possible lead researchers responsible for RCTs at the institute. The researchers have more than a basic knowledge of trial registries and their aims. All the researchers reported that they know of the ClinicalTrials.gov registry and most of them reported that they frequently use it; however, only a few know about the World Health Organization's registry platform (International Clinical Trials Registry Platform). The most cited registry aims reported were increased transparency and reduced publication bias. Of the studies registered in the institute's registry, 92% had at least one data item missing in the registry record. Concerning trial registration in the international registries, all 12 respondents said their trial had been registered and specified the registry name, but often they had not inputted the associated trial ID code in the corresponding field of the institute's registry. Concerning two important issues on data transparency and ethical standards, namely registration timing and result reporting, 11 stated that their trial was registered before starting recruitment, and for five of six closed trials they stated that their results have been already published-for one trial within 1 year after its completion. CONCLUSIONS: Researchers should guarantee correct reporting of trials and their data as a rule of great ethical value. Institutional self-audits should be performed periodically in order to improve clinical trial disclosure.

Clinical trial registries: more international, converging efforts are needed.

Clinical trial registries are being increasingly acknowledged worldwide. We searched for possibly trustworthy online registries that are not already included in the International Clinical Trials Registry Platform to evaluate whether other useful trial data sources exist and whether they could potentially be consulted, since the strategy search within this platform has recently been questioned. Fifty-nine registries were initially identified, and 11 of them fit the criteria applied and were analyzed for quality and usability. Four additional, potentially reliable registries were identified that researchers could exploit in order to obtain a more global view of the issue being investigated.

The evolution in registration of clinical trials: a chronicle of the historical calls and current initiatives promoting transparency.

PURPOSE: Quality of care is strongly influenced by evidence-based medicine, a large part of which is based on results obtained from clinical trials. If trials are conducted in secret, patient safety is at risk. Several mandates-legal, editorial, financial, and ethical-have tried to influence the disclosure of clinical trials, first by encouraging registration in publicly accessible registers and, second, by calling for the publication of results. Not all these initiatives have reached high rates of compliance, but the succession of national and international events over a few years gave an important boost to information disclosure. This article provides a chronicle of the succession of the events, from the historical calls to the recent EMA policy and WHO statement, and public consultations requested by the NIH, and the HHS, which will inevitably change the international panorama. The path of these new policies is moving towards more supervised clinical research. Individual scientific institutions can also contribute, at the local level, to such an ethical endeavor as is improving research transparency, by disclosing information on the trials coordinated by their own researchers. RESULTS: The way is long and complex, but, if everyone contributes there could be a prompt, worldwide diffusion of the findings of clinical trials, and therefore a more possible evidenced-based medicine.

Tuberculosis care for pregnant women: a systematic review.

BACKGROUND: Tuberculosis (TB) during pregnancy may lead to severe consequences affecting both mother and child. Prenatal care could be a very good opportunity for TB care, especially for women who have limited access to health services. The aim of this review was to gather and evaluate studies on TB care for pregnant women. METHODS: We used a combination of the terms "tuberculosis" and "pregnancy", limited to human, to search for published articles. Studies reflecting original data and focusing on TB care for pregnant women were included. All references retrieved were collected using the Reference Manager software (Version 11). RESULTS: Thirty five studies were selected for review and their data showed that diagnosis was often delayed because TB symptoms during pregnancy were not typical. TB prophylaxis and anti-TB therapy appeared to be safe and effective for pregnant women and their babies when suitable follow up and early initiation were present, but the compliance rate to TB prophylaxis is still low due to lack of follow up and referral services. TB care practices in the reviewed studies were in line in principle with the WHO International Standards for Tuberculosis Care (ISTC). CONCLUSIONS: Integration of TB care within prenatal care would improve TB diagnosis and treatment for pregnant women. To improve the quality of TB care, it is necessary to develop national level guidelines based on the ISTC with detailed guidelines for pregnant women.

Ureaplasma, bronchopulmonary dysplasia, and azithromycin in European neonatal intensive care units: a survey.

A survey was set up to gauge the opinions of neonatologists on the role of Ureaplasma in bronchopulmonary dysplasia (BPD) development, the use of azithromycin for BPD prevention, and the factors influencing azithromycin use in European neonatal intensive care units (NICUs). 167 NICUs participated in the survey, representing 28 European countries. For respondents, the two major perceived risk factors for BPD were prematurity of <28 weeks and high oxygen requirements. Only 38% of NICUs had a protocol for BPD prevention and 47% routinely tested for Ureaplasma. In cases of infection, macrolides were the first choice. Most (78%) NICUs were interested in participating in a trial evaluating azithromycin safety and efficacy in reducing BPD rates. Opinions and clinical practice varied between European neonatal units, and differences in Ureaplasma treatment and prevention of BPD highlight the need for further azithromycin evaluation and for improved therapeutic knowledge in preterms.

Clinical trial registries: from an omen to a common and disclosed practice.

OBJECTIVE: Clinical trials registries are important for guaranteeing trustworthy scientific knowledge. Despite international initiatives promoting trial registration, however, complete and high quality disclosure of trial information in such registries is not routine. The role of registries in also increasing transparency is fundamental, and these databases could be contemplated by research organizations, even at more local levels. METHODS: A rare initiative was set up at the IRCCS-Mario Negri Institute for Pharmacological Research in Milan in order to make the institute's ongoing research accessible to anyone. RESULTS: The register currently includes 112 studies in which the institute participates. CONCLUSIONS: Work still needs to be done to improve the registry, but it is up and functional. Could, or should, such registries be routine for all scientific institutions?

The use of ciprofloxacin and fluconazole in Italian neonatal intensive care units: a nationwide survey.

BACKGROUND: Treatment and prophylaxis of sepsis in very low birth weight neonates is a matter of concern and research is being undertaken with the aim to give rise to shared approaches based on solid evidence. As part of a European initiative, a survey was set up to describe the use of two drugs in this area. The Italian national practices concerning neonatal sepsis, as well as calls for related guidance, are described. METHODS: A standardized and previously tested questionnaire was submitted online to all Italian level III NICUs. A 5-point Likert scale was used to analyze attitudinal replies. Categorical variables were compared by χ2 analysis and 2-tailed P-values are reported. RESULTS: Data was provided by 38 Italian NICUs (36% of the country's level III centers), 53% of which have 1-10 cases of bacterial sepsis monthly and 90% a prevalence of <1% fungal infections. Ciprofloxacin and fluconazole treatment for neonatal sepsis are scantly used in Italian NICUs (13% and 45%, respectively). Major concerns are related to the safety of ciprofloxacin and the efficacy of fluconazole. On the contrary, prophylaxis of fungal infections is a routine approach in many Italian NICUs. The use of both ciprofloxacin and fluconazole is characterized by a large inter-NICU variability in dose and scheme of use. The lack of adequate, shared evidence is a common consideration made by the survey participants. CONCLUSIONS: Common approaches are needed to standardize and update a national drug strategy for the prevention and treatment of sepsis in very low birth weight newborns. This can be achieved through collaborative initiatives aimed at setting up guidelines, based on available data, and multicenter trials to produce new evidence that will address the knowledge gaps.

Wide intra- and inter-country variability in drug use and dosage in very-low-birth-weight newborns with severe infections.

PURPOSE: To describe the use of ciprofloxacin and fluconazole for the treatment of sepsis in European neonatal intensive care units (NICUs) in order to better orient research aimed at acquiring essential knowledge in this critical area. METHODS: The survey consisted of an online questionnaire for all participating NICUs on treatment schemes employed, rationales behind drug choices and interest in participation in research involving the two drugs. RESULTS: A total of 189 level II and III NICUs participated in the survey, representing 25 countries, with Italy, UK and France providing the greatest number of centres (54 % of total). Ciprofloxacin is used in 25 % of NICUs that responded, although the indications for administering it vary between centres and the dosage ranges vary considerably, with 25 % of NICUs giving ≤10 mg/kg/day and another 25 % giving ≥21 mg/kg/day. Factors given as affecting the decision to use ciprofloxacin are uncertainty about its safety and pharmacokinetics and level of penetration in the cerebrospinal fluid. Among the 70 % of responding units that use fluconazole to treat fungal infection, 45 % administer 6 mg/kg unit doses while 33 % administer 12 mg/kg; 41 % of NICUs use a 24-h interval between administrations while 20 % wait 72 h. Among the responding NICUs, 57 % were willing to participate in a project on ciprofloxacin and 59 % would consider participating in a randomized controlled trial evaluating fluconazole versus micafungin. CONCLUSIONS: Great variability in therapies exists within and between countries. Numerous centres are interested in participating in research on these drugs, highlighting the need for further knowledge on sepsis treatment and European centres' interest in off-patent medicine research.