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BackgroundThe thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed.ObjectiveTo compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth.Study design and settingMulticentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals.ParticipantsInfants with estimated birth weight +6weeks.InterventionThermal management with or without a thermal servo-controlled system during stabilisation in the delivery room.Primary outcomeProportion of normothermia at NICU admission (axillary temperature 36.5°C–37.5°C).ResultsAt NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C–36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01).ConclusionsIn very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge.Trial registration numberNCT03844204

Purpose: To evaluate associations between CD4/CD8 ratio and pregnancy outcomes in women with HIV. Methods: We evaluated, in a national study of pregnant women with HIV receiving antiretroviral treatment (ART), values of CD4/CD8 ratio at entry in pregnancy, changes between first and third trimester, and possible associations with preterm delivery, low birthweight, and HIV-RNA < 50 copies/ml at third trimester in univariate and multivariate analyses. Results: Among 934 women, 536 (57.4%) were already on ART at conception. CD4/CD8 ratio (baseline value 0.570) increased significantly between the first and third trimesters, particularly in women who started ART in pregnancy (+ 0.163, vs. + 0.036 in women already on treatment). The rate of CD4/CD8 ratio normalization, defined by achieving a ratio ≥ 1 at the third trimester, was 13.2%. In multivariable analyses, women who entered pregnancy with a CD4/CD8 ratio < 0.3, compared to women with ratio ≥ 1, were almost four-times less likely to have third-trimester HIV-RNA < 50 copies/ml (AOR 0.258, 95%CI 0.111–0.601), and more than twice as likely to have preterm delivery (AOR 2.379, 95%CI 1.082–5.232). For preterm delivery, also a baseline CD4/CD8 ratio between 0.3 and 0.45 was significantly associated with an increased risk (AOR: 3.415, 95%CI 1.690–6.900). Conclusion: We described for the first time independent associations of low CD4/CD8 ratio with preterm delivery and HIV-RNA suppression.

Background Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P

Congenital/perinatal nervous system (CNS) infections are an important cause of mortality and morbidity in neonatal period, and long-term sequelae. Many pathogens can lead to infections frequently involving the CNS, with possible disruption of brain development, which often is related to gestational age of maternal infection. The mechanism of infection and damage is different among the infectious agents, leading to more specific pathologic findings. It is necessary in newborns with confirmed or suspected CNS infection to undergo investigation by neuroimaging techniques to help healthcare providers, give adequate treatment and follow-up care and counsel parents. Computed tomography, Magnetic Resonance Imaging and cerebral ultrasonography are fundamental tools in evaluating infants with suspected or proved congenital/perinatal infections. Each imaging technique has its advantages, disadvantages and limits, since they are sometimes complementary.

BACKGROUND: Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. METHODS: Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. RESULTS: The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P < 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P < 0.001). CONCLUSIONS: In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options.

Objectives: Congenital Toxoplasmosis (CT) in newborns results from primary maternal infection with Toxoplasma gondii (TG). Many infected children are asymptomatic at birth but at high risk of neurological sequelae during early childhood. In case of missed diagnosis at birth, retrospective testing of neonatal Guthrie cards for TG DNA or specific IgM anti-TG detection could help to distinguish congenital from acquired Toxoplasmosis. The aim of the this study was to investigate the sensitivity and specificity of IgM testing by Western Blot (WB) and DNA amplification in dried blood samples (DBS) of infants born from mothers infected by TG during pregnancy. Methods: A retrospective study was performed in 18 infants born from mothers who acquired toxoplasmosis during the second or third trimester of pregnancy. At birth, all mother-child serum pairs were tested by conventional assays (Enzygnost Toxoplasmosis-Siemens; Vidas Toxo-bioMérieux) and by comparative WB (Toxoplasma WB IgG/IgM-LDBio Diagnostics). We collected Guthrie cards of every child (informed consensus was obtained from parents); one DBS was used for TG DNA detection and another one for antibodies elution. Nucleic acids were extracted from DBS with Versant kPCR Sample Preparation system (Siemens) and Toxoplasma Q-PCR Alert Kit (Nanogen) was used for amplification. Specific IgM anti-TG were detected in eluates from DBS by using LDBio Toxoplasma WB IgM. Results: At birth CT was diagnosed in 8 of the 18 newborns, because of IgM/IgA positivity and/or different IgG WB pattern in infant’s serum compared to the corresponding mother’s one. CT was excluded in the remaining 10 children because of their sera were IgM/IgA negative and their IgG titres decreased during the follow-up period; at 1 year of age all these 10 babies were IgG negative. In the present study, we confirmed CT in 4 out of the 8 CT cases. In particular, we were able to amplify TG DNA from one of the cards, while in other 3 cases we found specific IgM anti-TG. Specificity of DBS examination was 100%, since no TG DNA or IgM was found in the group of 10 non-infected babies. Serological test at birth and Guthrie card results of the 8 CT cases are shown in detail in table 1. Conclusions: Although serological evaluation at birth and during the first year remains basic for the laboratory diagnosis ofCT, examination of Guthrie cards could be considered a retrospective method to evaluate infants (>1 year ofage) with clinical signs suggestive of CT.

Human cytomegalovirus (CMV) is the most common cause of intrauterine infection, occurring in 0.2% to 2.2% of all live births, and congenital infection is a common cause of sensorineural hearing loss and mental retardation. Transmission to fetus may occur through primary or secondary maternal infection with a probability of 30% to 40%, intrauterine transmission following primary infection during pregnancy compared with 0.5% to 2.2 % following secondary infection. Approximately 10-15% of congenitally infected babies are symptomatic at birth and these infants have a perinatal mortality rate of around 10% with 70-80% of surviving babies presenting major neurological sequelae. Despite infection, 85-90% of babies have no symptoms at birth however 8-15% of them will suffer from psychomotor and sensory-neural disabilities. The management of congenital CMV infections varies considerably in different centers and often there are unequal methods used between practitioners, which can lead to substantial discrepancies between the indications suggested by the literature and what is actually performed. A multidisciplinary group of 30 experts and/or qualified representatives of the six Italian Scientific Societies of Clinical Microbiologists (AMCLI), Gynaecology and Obstetrics (SIGO), Sexually Transmitted Diseases (SIMaST), Infectious and Tropical Diseases (SIMIT), Neonatology (SIN) and Pediatrics (SIP) developed evidence and expert opinion-20 based consensus guidelines on CMV congenital infection management including mechanism of pathogenesis, clinical and epidemiological aspects, prevention, diagnostics, and treatments. Each section used a scoring system to rate the quality of evidence on which recommendations are based.The document was prepared, discussed and validated by multidisciplinary committee through a consensus conference

AIMS Congenital Toxoplasmosis (CT) in newborns results from primary maternal infection with T. gondii (TG). Most infected children show no symptoms at birth but are at great risk of sequelae during the first year of life or in early childhood [1]. Polymerase chain reaction (PCR) analysis of dried blood samples on the Guthrie card has been proposed as a sensitive method to screen for congenital CMV infection, but there are no data about the use for TG screening. The aim of present study was to assess the utility of PCR analysis of dried blood samples for the retrospective diagnosis of CT. METHODS A retrospective study was performed with 18 infants born between January 2010 and June 2012. Transmitters mothers seroconverted in the second trimester of pregnancy (mean 23.5 ± 7.9 weeks). At birth, serological tests (Enzygnost Toxoplasmosis IgG, IgM, IgA-Siemens Healthcare Diagnostics; Vidas Toxo IgMbioMerieux) as well as IgM-IgG WB (LDBio Toxoplasma WB IgG/IgM-LDBio Diagnostics) were performed in all mother-child pairs.Nucleic acids were extracted from Guthrie cards with VERSANT kPCR Sample Preparation system (Siemens) and Toxoplasma Q-PCR Alert Kit (Nanogen) was used for the amplification of TG target region AF 146527. RESULTS In 7/18 (38.9%) infants, CT was diagnosed by IgM-WB positivity at birth. The remaining 11 were considered non-infected (61.1%) and became IgG negative within 12 months of life. Infected infants received one-year therapy (pyrimethamine/sulfadiazine) and were followed according to our protocol. Four of these had a pathological neuroimaging (4/4 calcifications, 2/4 ventriculomegaly). None had hearing loss. TG DNA was detected in only one of the Guthrie cards of the infected newborns, while all the others were negative. CONCLUSIONS Although serological methods remain basic in the diagnosis of CT, TG DNA detection in Guthrie cards could be considered a retrospective method to evaluate infants (> 1 year of age) with clinical signs suggestive of CT. More studies with a larger number of infected cases are needed to assess the sensitivity of this method.

AIMS Chlamydia trachomatis is one of the most common sexually transmitted agents. Infants born vaginally to infected mothers may present with conjunctivitis (20-50%) and/or pneumonia (5-20%) [1]. Chlamydia spp. is a frequent identifiable cause of neonatal conjunctivitis, in association with S. aureus, E. coli, N. gonorrhoeae. Topical eye drops such as silver nitrate 1% effectively prevent gonococcal neonatal conjunctivitis; however, antibiotic topical agents are commonly used in the clinical practice in the attempt to prevent also chlamydial infections. METHODS Topical ocular prophylaxis with fusidic acid was instituted early after birth. Data about new cases of chlamydial conjunctivitis from September 2011 to August 2012 were recorded. Data included length and course of pregnancy, maternal diseases, delivery method, newborn weight, postnatal course. RESULTS Two cases of isolated chlamydial conjunctivitis were recorded. Both infants (one male, one female) were born by vaginal delivery. They were full term, healthy infants,without ocular malformations, whose mothers were treated with neither systemic nor local antibiotics near delivery. Birth weight: 3,400 and 2,380 g respectively. Pregnancy courses are unknown. Both infants received antibiotic prophylaxis in each eye 20 minutes after delivery. The age of presentation for conjunctivitis was between day 10 and 12 of life. Infants presented with hyperemic conjunctiva, mucopurulent discharge and swollen eyelids. The male infant also had blood-stained eye discharge. Ophthalmological examinations showed follicular conjunctivitis. Definite diagnosis was made by detection of Chlamydia DNA by PCR on specimens obtained by swabbing the conjunctiva. Both infants were treated with systemic Clarithromycin at 10 mg/kg/day in 2 doses for 14 days, after an electrocardiogram was performed. No long-term ocular sequelae were found. CONCLUSIONS In addition to the typical features of chlamydial conjunctivitis, a follicular conjunctivitis was demonstrated at ophthalmological examination in both our neonates. Prophylaxis with fusidic acid did not prevent all cases of chlamydial neonatal conjunctivitis. In the absence of information about pregnancy, screening for Chlamydia spp. may be an effective practice to prevent neonatal infection and related complications.

Each year approximately 1–7% of pregnant women acquire a primary cytomegalovirus (CMV) infection. Of these, about 30–40% transmit infection to their fetuses. Up until some years ago it was not possible to precisely define the maternal immune status through laboratory testing. Recent development of advanced serological tests now allow us to identify, among pregnant women with suspected CMV, those with primary infection who are therefore at higher risk of transmitting CMV to their fetus. Given the high risk of mother–fetus transmission and fetal damage, prenatal diagnosis is recommended, between 20-21 weeks’ gestation, to women with primary CMV infection contracted in the first half of pregnancy and/or in case of fetal abnormalities suggestive of infection. CMV-DNA detection in amniotic fluid (AF) distinguish uninfected from infected fetuses in primarily infected mothers (positive predictive value =100%). However it is still very difficult to determine which are the infected foetuses at higher risk of developing severe CMV disease. In this work we studied a cohort of 790 pregnancies at risk of in utero CMV transmission; 796 amniotic fluid (AF) samples were tested by real time PCR assay (qPCR) and virus isolation. AF samples were collected at 20-21 weeks' gestation and at least 6-8 weeks after the onset of maternal CMV infection. Outcome was fully documented in 714 newborns and 82 foetuses. A total of 108 newborns were CMV infected; 25 were 119 symptomatic and 83 asymptomatic. Comparing symptomatic and asymptomatic newborns, the mean viral load in AF was significantly higher in symptomatic newborns (mean values 2x10^6 vs 9.4x10^5, P=0.009). The 82 infected foetuses were divided in two groups: those with histological damage in the brain and in 2 or more organs and those with histological damage in only 2 or more organs. When qPCR disclosed more than 10^6 copies/mL of AF, 62.5% of foetuses had disseminated infection and brain damage compared to 29.4% of foetuses with disseminated infection alone. Although the highest median values of CMV-DNA in AF tend to indicate an increased risk of severe infection, high viral loads may be associated with symptomatic or asymptomatic congenital infections leading to the conclusion that a correlation between a high CMV load in AF and foetal/neonatal compromission is uncertain. Recent studies suggest that the determination of multiple markers (haematological, biochemical and virological markers) in foetal blood following virus detection in AF, is predictive of perinatal outcome of CMV infected foetuses. However our results do not completely confirm this. Therefore, one of the major limitations of CMV prenatal diagnosis is that we are not able to discriminate between infants who will or will not have symptoms at birth. Prognosis factors for CMV disease are still being researched. In this regards, we found interesting results studying the HLA-G antigen, which is a tolerogenic HLA-Ib molecule expressed during pregnancy. HLA-G expression is modified by CMV infection, with functional consequences in immuno-regulation. Data indicates that this molecule could be a biomarker of both maternal and foetal infection and leading to disease progression