Diaphragmatic hernia in a term newborn with congenital myotonic dystrophy: case report.

Background and aim Myotonic dystrophy (DM) is a genetic disorder determined by an amplified trinucleotide CTG repeat in the untranslated region of the DMPK gene on chromosome 19q13.3. The incidence of the congenital form is 1 in 47619 live births and the mortality in the neonatal period is up to 40%. Methods: We report a case of congenital DM (CDM, also designated Myotonic Dystrophy Type 1), presented with congenital right diaphragmatic hernia and cerebral bilateral ventricular dilatation, genetically diagnosed. Conclusions: Since no case of congenital diaphragmatic hernia associated with CDM is reported, the present case report could be considered of particular interest.

Delayed Start of Routine Vaccination in Preterm and Small-for-Gestational-Age Infants: An Area-Based Cohort Study from the Tuscany Region, Italy.

Preterm and small-for-gestational-age (SGA) infants are more susceptible to vaccine-preventable diseases. To evaluate routine vaccination timeliness in these high-risk groups, a full birth cohort of infants (n = 41,502) born in 2017 and 2018 in Tuscany was retrospectively followed up until 24 months of age. Infants were classified by gestational age (GA) and SGA status. The vaccinations included: hexavalent (HEXA), measles-mumps-rubella, varicella, pneumococcal conjugate (PCV), and meningococcal C conjugate. Time-to-event (Kaplan-Meier) analyses were conducted to evaluate the timing of vaccination according to GA; logistic models were performed to evaluate the associations between GA and SGA with vaccination timeliness. Time-to-event analyses show that the rate of delayed vaccine receipt increased with decreasing GA for all the vaccinations, with a less marked gradient in later vaccine doses. Compared to full-term infants, very preterm infants significantly showed an increased odds ratio (OR) for delayed vaccination in all the vaccinations, while moderate/late preterm infants only showed an increased OR for HEXA-1, HEXA-3, PCV-1, and PCV-3. SGA infants had a significantly higher risk of delayed vaccination only for HEXA-1 and PCV-1 compared to non-SGA infants. In conclusion, vaccinations among preterm and SGA infants showed considerable delay. Tailored public health programs to improve vaccination timeliness are required in these high-risk groups.

Safety use of high frequency oscillatory ventilation in transport of newborn infants affected by severe respiratory failure: preliminary data in central Tuscany.

BACKGROUND: Neonatal Emergency Transport Services play a fundamental role in neonatal care. Stabilization before transport of newborns suffering from severe respiratory failure is often a challenging problem and some critically ill infants may benefit from High Frequency Oscillatory Ventilation (HFOV) as rescue treatment. In these cases, transition to conventional ventilation for transport may cause a deterioration in clinical conditions. HFOV during neonatal transport has been only exceptionally used, due to technical difficulties. Since May 2018, a new neonatal transport unit is available at the Neonatal Protected Transport Service of the Meyer University Hospital in Florence, equipped with a pulmonary ventilator capable of delivering HFOV. Therefore, we conducted an analysis on patients transferred in HFOV to Neonatal Intensive Care Unit (NICU), in order to evaluate the safety and feasibility of its use during neonatal transport. METHODS: A retrospective analysis was performed reviewing medical records of the neonates transported by Meyer Children Hospital's Neonatal Transport Service between May 2018 and December 2020, and newborns treated with HFOV during ground neonatal transport were identified. Safety was assessed by the comparison of vital signs, hemogas-analysis values and pulmonary ventilator parameters, at the time of departure and upon arrival in NICU. The dose of inotropes, the main respiratory complications (air leak, dislocation or obstruction of the endotracheal tube, loss of chest vibrations) and the number of deaths and transfer failures were recorded. RESULTS: Out of the approximate 400 newborns transported during the analysis period, 9 were transported in HFOV. We did not find any statistically significant difference in vital parameters, hemogas-analytical values and pulmonary ventilator settings recorded before and after neonatal transport of the nine patients' parameters (p > 0,05). No patient required additional inotropes during transport. No transport-related deaths or significant complications occurred during transport. CONCLUSIONS: The interest of our report is in the possibility of using HFOV during inter-hospital neonatal transfer. As far as our experience has shown, HFOV appears to be safe for the transportation of newborns with severe respiratory failure. Nevertheless, further larger, prospective and multicentre studies are needed to better evaluate the safety and efficacy of HFOV during neonatal transport.

International Variation in the Management of Patent Ductus Arteriosus and Its Association with Infant Outcomes: A Survey and Linked Cohort Study.

OBJECTIVE: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. STUDY DESIGN: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of <29 weeks of gestation born in 2014-2016 and admitted to tertiary neonatal intensive care units (NICUs) of 9 population-based national or regional neonatal networks. Infants in NICUs receiving treatment of presymptomatic PDA identified by routine echocardiography and those not were compared for the primary composite outcome (early death [≤7 days after birth] or severe intraventricular hemorrhage) and secondary outcomes (any in-hospital mortality and major morbidities). RESULTS: The unit survey (response rates of 86%) revealed a wide variation among networks in the treatment of presymptomatic PDA (7%-86%). Among 246 NICUs with 17 936 infants (mean gestational age of 26 weeks), 126 NICUs (51%) with 7785 infants treated presymptomatic PDA. The primary outcome of early death or severe intraventricular hemorrhage was not significantly different between the NICUs treating presymptomatic PDA and those who did not (17% vs 21%; aOR 1.00, 95% CI 0.85-1.18). The NICUs treating presymptomatic PDA had greater odds of retinopathy of prematurity treatment (13% vs 7%; aOR 1.47, 95% CI 1.01-2.12); however, it was not significant in a sensitivity analysis excluding Japanese data. CONCLUSIONS: Treating presymptomatic PDA detected by routine echocardiography was commonplace but associated with no significant benefits. Well-designed trials are needed to assess the efficacy and safety of early targeted PDA treatment.

Survey shows marked variations in approaches to redirection of care for critically ill very preterm infants in 11 countries.

AIM: We surveyed care practices for critically ill very preterm infants admitted to neonatal intensive care units (NICUs) in the International Network for Evaluating Outcomes in Neonates (iNeo) to identify differences relevant to outcome comparisons. METHODS: We conducted an online survey on care practices for critically ill very preterm infants and infants with severe intracranial haemorrhage (ICH). The survey was distributed in 2015 to representatives of 390 NICUs in 11 countries. Survey replies were compared with network incidence of death and severe ICH for infants born between 230/7 and 286/7  weeks of gestation from January 1, 2015, to December 31, 2015. RESULTS: Most units in Israel, Japan and Tuscany, Italy, favoured withholding care when care was considered futile, whereas most units in other networks favoured redirection of care. For infants with bilateral grade 4 ICH, redirection of care was very frequently (≥90% of cases) offered in the majority of units in Australia and New Zealand and Switzerland, but rarely in other networks. Networks where redirection of care was frequently offered for severe ICH had lower rates of survivors with severe ICH. CONCLUSION: We identified marked inter-network differences in care approaches that need to be considered when comparing outcomes.

Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297- 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a ß-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration  The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

Feeding Practices in Very Preterm and Very Low Birth Weight Infants in an Area Where a Network of Human Milk Banks Is in Place.

Background: Great variability in enteral feeding practices for very preterm (<32 weeks gestational age-GA) and very low birth weight infants (VLBW; ≤1,500 g) have been reported. We aimed to describe data on enteral feeding in Tuscany (Italy), where a network of 6 donor milk banks is in place. Methods: A 4-years (2012-2015) observational study was performed analyzing the database "TIN Toscane online" on very preterm and VLBW infants. The database covers all 25 hospitals with a neonatal unit. Results: Data concerning the beginning of enteral nutrition were available for 1,302 newborns with a mean (standard deviation) GA of 29.3 (2.9) weeks, while information at the time of full enteral nutrition was available for 1,235 and at discharge for 1,140. Most infants (74.1%) started enteral feeding during the first 24 h of life. Overall, 80.1% of newborns were fed exclusive human milk, donor milk having the larger prevalence of use (66.8%). Few infants (13.3%) started with exclusive mother's milk. Full enteral feeding was achieved using exclusive human milk in most cases (80%). Full enteral feeding was reached earlier in newborns who were fed human milk than in those fed formula, regardless of GA. Sixty-four percent of infants were still fed with any human milk at discharge. When data at the achievement of full enteral nutrition and at discharge were analyzed stratified by the type of milk used to start enteral feeding, newborns initially fed donor milk presented the highest prevalence (91.3%) of exclusive human milk at full enteral feeding, an important period to prevent necrotizing enterocolitis, while no differences were observed at discharge. Conclusions: Donor milk was widely used for newborns during the first hours of life, when mother's milk availability may be quite challenging. Starting enteral nutrition with donor milk was associated with early start of enteral feeding and early achievement of full enteral nutrition without affecting mother lactation. The overall prevalence of human milk at discharge (when donor milk is not available anymore) was high (64%), irrespective of the type of milk used to start nutrition.

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): a feasibility study.

PURPOSE: To investigate the feasibility of a study based on treatment with topiramate (TPM) added to moderate hypothermia in newborns with hypoxic ischemic encephalopathy (HIE). MATERIALS AND METHODS: Multicenter randomized controlled trial. Term newborns with precocious metabolic, clinical and electroencephalographic (EEG) signs of HIE were selected according to their amplified integrated EEG pattern and randomized to receive either TPM (10 mg/kg once a day for the first three days of life) plus moderate hypothermia or hypothermia alone. Safety was assessed by monitoring cardiorespiratory parameters and blood samples collected to check renal, liver, metabolic balance and TPM pharmacokinetics. Efficacy was evaluated by the combined frequency of mortality and severe neurological disability as primary outcome. Incidence of magnetic resonance injury, epilepsy, blindness, hearing loss, neurodevelopment at 18-24 months of life was assessed as secondary outcomes. RESULTS: Forty-four asphyxiated newborns were enrolled in the study. Twenty one newborns (10 with moderate and 11 with severe HIE) were allocated to hypothermia plus TPM and 23 (12 moderate and 11 severe HIE) to hypothermia. No statistically or clinically significant differences were observed for safety, primary or secondary outcomes. However, a reduction in the prevalence of epilepsy was observed in newborns co-treated with TPM. CONCLUSIONS: Results of this pilot trial suggest that administration of TPM in newborns with HIE is safe but does not reduce the combined frequency of mortality and severe neurological disability. The role of TPM co-treatment in preventing subsequent epilepsy deserves further studies.

Study protocol: safety and efficacy of propranolol 0.2% eye drops in newborns with a precocious stage of retinopathy of prematurity (DROP-ROP-0.2%): a multicenter, open-label, single arm, phase II trial.

BACKGROUND: Retinopathy of prematurity (ROP) still represents one of the leading causes of visual impairment in childhood. Systemic propranolol has proven to be effective in reducing ROP progression in preterm newborns, although safety was not sufficiently guaranteed. On the contrary, topical treatment with propranolol eye micro-drops at a concentration of 0.1% had an optimal safety profile in preterm newborns with ROP, but was not sufficiently effective in reducing the disease progression if administered at an advanced stage (during stage 2). The aim of the present protocol is to evaluate the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns at a more precocious stage of ROP (stage 1). METHODS: A multicenter, open-label, phase II, clinical trial, planned according to the Simon optimal two-stage design, will be performed to analyze the safety and efficacy of propranolol 0.2% eye micro-drops in preterm newborns with stage 1 ROP. Preterm newborns with a gestational age of 23-32 weeks, with a stage 1 ROP will receive propranolol 0.2% eye micro-drops treatment until retinal vascularization has been completed, but for no longer than 90 days. Hemodynamic and respiratory parameters will be continuously monitored. Blood samplings checking metabolic, renal and liver functions, as well as electrocardiogram and echocardiogram, will be periodically performed to investigate treatment safety. Additionally, propranolol plasma levels will be measured at the steady state, on the 10th day of treatment. To assess the efficacy of topical treatment, the ROP progression from stage 1 ROP to stage 2 or 3 with plus will be evaluated by serial ophthalmologic examinations. DISCUSSION: Propranolol eye micro-drops could represent an ideal strategy in counteracting ROP, because it is definitely safer than oral administration, inexpensive and an easily affordable treatment. Establishing the optimal dosage and treatment schedule is to date a crucial issue. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02504944, registered on July 19, 2015, updated July 12, 2016. EudraCT Number 2014-005472-29.

Propranolol 0.1% eye micro-drops in newborns with retinopathy of prematurity: a pilot clinical trial.

BACKGROUND: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. This study evaluated safety and efficacy of propranolol eye micro-drops in preterm newborns with ROP. METHODS: A multicenter open-label trial, planned according to the Simon optimal two-stage design, was performed to analyze safety and efficacy of propranolol micro-drops in newborns with stage 2 ROP. To this end, hemodynamic and respiratory parameters were monitored, and blood samples were collected weekly, for 3 wk. Propranolol plasma levels were also monitored. The progression of the disease was evaluated with serial ophthalmologic examinations. RESULTS: Twenty-three newborns were enrolled. Since the fourth of the first 19 newborns enrolled in the first stage of the study showed a progression to stage 2 or 3 with plus, the second stage was prematurely discontinued. Even though the objective to complete the second stage was not achieved, the percentage of ROP progression (26%) was similar to that obtained previously with oral propranolol administration. However, no adverse effects were observed and propranolol plasma levels were significantly lower than those measured after oral administration. CONCLUSION: Propranolol 0.1% eye micro-drops are well tolerated, but not sufficiently effective. Further studies are required to identify the optimal dose and administration schedule.

Successful Propranolol Treatment of a Kaposiform Hemangioendothelioma Apparently Resistant to Propranolol.

A newborn with unresectable kaposiform hemangioendothelioma associated with Kasabach Merritt phenomenon, unresponsive to vincristine and prednisone, received second-line treatment with propranolol at a dose of 2 mg/kg/day, starting at 2 months of life and continued for 13 months. There was only slight reduction in tumor mass, but measurement of propranolol levels showed extremely low plasma concentrations. The propranolol dose was progressively increased to 3.5 mg/kg/day, leading to a substantial increase in plasma levels associated with clinically relevant tumor reduction. This case highlights the importance of relating propranolol dose to its plasma concentration before considering the treatment ineffective for this vascular tumor.

Performance of a non-contact infrared thermometer in healthy newborns.

OBJECTIVE: To evaluate the performance of a non-contact infrared thermometer (NCIT) in comparison with digital axillary thermometer (DAT) and infrared tympanic thermometers (ITT) in a population of healthy at term and preterm newborns nursed in incubators. SETTING: 1 level III maternity hospital, and its intensive neonatal care unit. PARTICIPANTS: 119 healthy at term newborns and 70 preterm newborns nursed in incubators were consecutively enrolled. Exclusion criteria were unstable/critical conditions, polymalformative congenital syndromes and severe congenital syndromes. INTERVENTIONS: Body temperature readings were prospectively collected. Each participant underwent bilateral axillary temperature measurement with DAT, bilateral tympanic measurement with ITT and mid-forehead temperature measurements using NCIT. PRIMARY OUTCOME MEASURES: Degree of agreement between methods was evaluated by the Bland and Altman method. RESULTS: 714 measurements in 119 healthy at term newborns and 420 measurements in 70 preterm newborns nursed in incubators were performed. Clinical reproducibility of NCIT was 0.0455 °C for infants in incubators and 0.0861 °C for infants outside an incubator. Bias was 0.029 °C for infants in incubators and <0.0001 °C for infants outside an incubator. Zero outliers were recorded. The mean difference between methods was good both for newborns at term (0.12 °C for NCIT vs DAT and 0.02 °C for NCIT vs ITT) and preterm newborns in incubators (0.10 °C for NCIT vs DAT and 0.14 °C for NCIT vs ITT). Limits of agreement were 0.99 to -0.75 and 0.78 to -0.75 in at term newborns and were particularly satisfactory in preterm newborns in incubators (95% CI: 0.48 to -0.27 and 0.68 to -0.40). CONCLUSIONS: Our results with Bland and Altman analysis demonstrate that NCIT is a very promising tool, especially in preterm newborns nursed in incubators. TRIAL REGISTRATION: The study was approved by the Careggi University Hospital Ethics Committee (07/2011).

Comparison of the transcutaneous bilirubinometers BiliCare and Minolta JM-103 in late preterm and term neonates.

OBJECTIVES: To assess the agreement of transcutaneous bilirubin (TcB) measurement with the Bilicare™ System in comparison to TcB measured with JM-103™ and total serum bilirubin (TSB). METHODS: Caucasian infants with gestational age ≥35 weeks with non-hemolytic jaundice received TcB measurement with both Bilicare™ and JM-103™ devices. TSB was also obtained in infants at risk of phototherapy. RESULTS: We studied 458 infants measuring TcB with Bilicare™ and JM-103™, correlating the results and with TSB. The mean difference ± 2SD between Bilicare™ and JM-103™ TcB was 2.02 ± 4.46 mg/dL and decreased from 2.88 ± 3.17 to 1.20 ± 4.55, and to -0.95 ± 4.58 mg/dL at mild, moderate and high TcB values, respectively. CONCLUSIONS: Bilicare™ and JM-103™ TcB measurements are well correlated, but Bilicare™ over-estimates TcB for mild and moderate values and under-estimates it for high values compared to JM-103™. This could increase the prescription of TSB measurements for less serious cases and decrease them in the most worrisome.

What steps do we need to take to improve diagnosis of tuberculosis in children?

Tuberculosis still represents a big global public health challenge. The diagnosis of tuberculosis and the differentiation between active and latent tuberculosis remain difficult, particularly in childhood, because of the lack of a gold standard test for diagnosis. In the last decade, novel diagnostic assays have been developed. Among immunologic tests, new assays based on the measurement of different cytokines released by specific T cells in response to Mycobacterium tuberculosis antigens, other than INF-γ, have been investigated. Promising results rely on nucleic acid amplification techniques, also able to detect drugs resistance. Innovative research fields studied the modifications of CD27 expression in T cells as well as different host gene expression in response to M. tuberculosis. Further studies are needed to assess the diagnostic value and the accuracy of these new assays.

The new face of the pediatric HIV epidemic in Western countries: demographic characteristics, morbidity and mortality of the pediatric HIV-infected population.

The natural history of the pediatric HIV epidemic has changed since the introduction of strategies for the prevention of mother-to-child transmission and the implementation of highly active antiretroviral therapy. The demographic characteristics of the pediatric HIV-infected population and the incidence and pattern of HIV-related morbidity, as well as mortality rates, have been remarkably modified. This report gives an overview on the main changes that occurred in Western countries.

Management and prevention of pertussis infection in neonates.

Despite the fact that universal immunization against pertussis led to a dramatic decrease in the incidence and mortality in high-income countries, it has left a window of vulnerability for newborns. Although specific guidelines concerning management of neonatal whooping cough have not yet been developed, the present review summarizes the main available recommendations on diagnostic work-up and treatment of neonatal pertussis. Additionally, new prevention strategies are explored, including the use of an additional booster dose of vaccine to adolescents and adults, vaccination of healthcare workers, immunization of household contacts and caregivers (cocooning strategy), vaccination of pregnant women and, finally, neonatal immunization with novel vaccines. These strategies are analyzed and discussed in terms of efficacy, safety and cost-effectiveness.

Pertussis is still common in a highly vaccinated infant population.

AIM: To provide epidemiological data on pertussis in a highly vaccinated paediatric population, focusing on the age of the infected children. METHODS: We analysed data from the regional hospital discharge database on children hospitalised for pertussis in Tuscany, Italy, from January 2000 to December 2012. RESULTS: A total of 279 cases were recorded. The majority of hospitalised children were infants (75.6%), who had the highest rate of complications (24.2%) of any age group and a crude mortality rate of 9.47 per 1000. The overall hospitalisation rate decreased significantly during the study period, from 4.23 to 2.82 per 100 000, but when we analysed the data by age groups, we found notable differences. Hospitalisation rates in the 1- to 4-year-old age group decreased significantly from 2.82 in the year 2000 to zero per 100 000 in 2012 and decreased significantly in the 5- to 9-year-old age group over the same period, from 6.58 to 0.63 per 100 000. Overall hospitalisation rates in the infant group remained high at 53.14 per 100 000, with three peaks due to periodic pertussis outbreaks. CONCLUSION: Pertussis is still a relevant health concern in infants who are unvaccinated or incompletely immunised, both in terms of morbidity and mortality.

Tuberculosis in childhood: a systematic review of national and international guidelines.

BACKGROUND: Paediatric tuberculosis (TB) represents a major public health concern worldwide. About 1 million children aged less than 15 years develop TB each year, contributing to 3-25% of the total TB caseload. The aim of this review is to evaluate national and international guidelines concerning tuberculosis in childhood and compare them in terms of diagnosis and treatment strategies. METHODS: A literature search of the Pubmed database was performed from January 2000 to August 2013, using the terms "tuberculosis" and "children". The search was limited to guidelines and consensus conferences, human species and full text availability, with no language restrictions. RESULTS: Twenty-seven national and international guidelines are identified. Several discrepancies on the diagnosis workup of TB are underlined. The main points of disagreement are represented by the interpretation of tuberculin skin test (TST) result and the recommendations on the use of TST and/or interferon-gamma release assay (IGRA) for the diagnosis of TB infection. Otherwise, all guidelines are in agreement that a microbiological confirmation should always be sought. Similarly, susceptibility drug testing and genotyping should be performed whenever it is possible on the basis of resources availability. On the contrary, the use of nucleic acid amplification tests (NAATs) for the M. tuberculosis detection is still controversial. A general consensus exists, otherwise, on TB treatment and only minor discrepancies are evidenced, such as the recommendations on daily or intermittent treatment regimens. CONCLUSIONS: Despite advances in TB diagnostic tools have been reached during the last decade, a lack of uniformity in their availability, indication and interpretation has relevant consequences for clinical practice. Further studies need to be performed to clarify this issue and identify a reliable and reproducible diagnostic workup. Moreover, future studies should analyze the drug metabolism and the efficacy of intermittent dosing regimes in childhood, as well as new treatment regimens in order to improve the therapy compliance.

Pediatric human immunodeficiency virus infection and cancer in the highly active antiretroviral treatment (HAART) era.

Highly active antiretroviral therapy (HAART) changed the natural history of pediatric HIV infection. This review focuses on trends of HIV-associated cancers in childhood in the HAART era and analyses potential pathogenetic mechanisms. HAART reduced AIDS-defined-malignancies (ADM), but incidence of several non-ADM is increasing. HIV-associated immune activation and inflammation, promoting tumorigenesis, can only partially be reduced by HAART. In addition, HIV-infected children may undergo accelerated immune senescence that favors cancer development. How HAART affects this condition is an open question. Lastly, there is no evidence that prenatal exposure to HAART increases the risk of cancer in childhood, but long-term studies are needed.