Toxoplasmosis in pregnancy in an area with low seroprevalence: is prenatal screening still worthwhile?

BACKGROUND: The effectiveness of Toxoplasma gondii (Tg) screening during pregnancy in areas with a low prevalence of the infection is debated. We investigate the Tg serological status, the rate of primary infection in a cohort of pregnant women and the rate of congenital toxoplasmosis among their infants during a 3-year period in an urban area with low Tg prevalence. METHODS: Demographic and Tg serological data for all pregnant women delivering from January 2009 to December 2011 were collected. All pregnant women with primary Tg infection during pregnancy and their infants were included in the study. RESULTS: In early pregnancy, 10,347 women underwent prenatal screening and 2308 (22.3%) had anti-Tg. The seroprevalence among non-native women was significantly higher than that among native women [32.8% vs. 19.1%, relative risk: 1.71, P < 0.001]. The incidence rate of primary Tg infection during pregnancy was 0.77%. Immigrant women were more likely to be infected during pregnancy than Italian women (relative risk: 4.88, P < 0.001). Tg infection was more frequent in women coming from Africa, Asia, Eastern Europe and South America. The CT incidence rate was 0.06%. All congenitally infected infants were born to immigrant mothers. CONCLUSIONS: Tg infection during pregnancy and congenital disease are more frequent in non-native mothers and their infants. Measures to prevent Tg exposition must be carefully explained to pregnant women, with a focus on specific habits in non-native women. Prenatal screening is still effective to select women for prenatal therapy aiming to decrease vertical transmission and to identify foetuses/newborns with congenital disease that could benefit from pre/postnatal antiparasitic therapy.

Human milk feeding prevents retinopathy of prematurity (ROP) in preterm VLBW neonates.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease, but little is known about its relationships with neonatal nutritional policies. Human, maternal milk is the best possible nutritional option for all premature infants, including those at high risk for severe complications of prematurity, such as ROP. OBJECTIVE: This is a secondary analysis of data collected during two multicenter RCTs performed consecutively (years 2004 through 2008) by a network of eleven tertiary NICUs in Italy. The two trials aimed at assessing effectiveness of fluconazole prophylaxis (Manzoni et al., N Engl J Med 2007 Jun 14;356(24):2483-95), and of bovine lactoferrin supplementation (Manzoni et al., JAMA 2009 Oct 7;302(13):1421-8), in prevention of invasive fungal infection, and of late-onset sepsis in VLBW infants, respectively. We tested the hypothesis that exclusive feeding with fresh maternal milk may prevent ROP of any stage - as defined by the ETROP study - in VLBW neonates, compared to formula feeding. METHODS: We analyzed the database from both trials. Systematic screening for detection of ROP was part of the protocol of both studies. The definition of threshold ROP was as defined by the ETROP study. Univariate analysis was performed to look for significant associations between ROP and several possible associated factors, and among them, the type of milk feeding (maternal milk or formula for preterms). When an association was indicated by p < 0.05, multiple logistic regression was used to determine the factors significantly associated with ROP. RESULTS: In both trials combined, 314 infants received exclusively human maternal milk (group A), and 184 a preterm formula because their mothers were not expected to breastfeed. The clinical, demographical and management characteristics of the neonates did not differ between the two groups, particularly related to the presence of the known risk factors for ROP. Overall, ROP incidence (any stage) was significantly lower in infants fed maternal milk (11 of 314; 3.5%) as compared to formula-fed neonates (29 of 184; 15.8%) (RR 0.14; 95% CI 0.12-0.62; p = 0.004). The same occurred for threshold ROP (1.3% vs. 12.3%, respectively; RR 0.19; 95% CI 0.05-0.69; p = 0.009). At multivariate logistic regression controlling for potentially confounding factors that were significantly associated to ROP (any stage) at univariate analysis (birth weight, gestational age, days on supplemental oxygen, systemic fungal infection, outborn, hyperglycaemia), type of milk feeding retained significance, human maternal milk being protective with p = 0.01. CONCLUSIONS: Exclusive human, maternal milk feeding since birth may prevent ROP of any stage in VLBW infants in the NICU.

Group B streptococcus late-onset disease: 2003-2010.

BACKGROUND: There is insufficient population-based data on group B streptococcus (GBS) late-onset disease (LOD). Risk factors and routes of GBS transmission are poorly understood. METHODS: A prospective, cohort study was conducted to collect incidence data on LOD and evaluate GBS infections over an 8-year period (2003-2010). Starting from January 2007, maternal rectovaginal and breast milk cultures were routinely collected on confirmation of the LOD diagnosis to assess maternal GBS culture status. RESULTS: The incidence rate of LOD was 0.32 per 1000 live births (1.4 and 0.24 per 1000 live births for preterm and term newborns, respectively). The registered cases of LOD (n = 100) were classified as sepsis (n = 57), meningitis (n = 36), or focal infection (n = 7). Thirty neonates were preterm (2 had recurrent infection); 68 were term. Four infants died (3 early preterm, 1 term). At the time the LOD diagnosis was confirmed, 3 (6%) of 53 mothers had GBS mastitis, and 30 (64%) of 47 carried GBS at the rectovaginal site. Early (7-30 days) LOD presentation was associated with neonatal brain lesions or death (odds ratio: 0.96 [95% confidence interval: 0.93-0.99]). Intrapartum antibiotic exposure was significantly associated with mild (12 of 22) rather than severe (11 of 45; P = .03) LOD. CONCLUSIONS: Preterm neonates had the highest rates of LOD and mortality. Most mothers carried GBS at the time of the LOD diagnosis, whereas 6% had mastitis. Intrapartum antibiotics were associated both with delayed presentation of symptoms and milder LOD.

Congenital syphilis in Italy: a multicentre study.

OBJECTIVE: To study the prevalence of congenital syphilis and its risk factors in Italy. STUDY DESIGN: Prospective study from 1 July 2006 to 30 June 2007. Data on mother-child pairs were collected for every syphilis seropositive mother. RESULTS: Maternal syphilis seroprevalence at delivery was 0.17%. 207 infants were born to 203 syphilis seropositive mothers. In 25 newborns it was possible to diagnose congenital syphilis (20/100,000 live births). Maternal risk factors included age <20 years, no antenatal care and no adequate treatment. The infected babies were more often preterm or weighed <2000 g at birth. DISCUSSION: Many syphilis seropositive mothers were foreign born but the risk of an infected newborn was not higher in foreign-born than in Italian seropositive women. The significant factors were lack of antenatal screening and inadequate maternal treatment. CONCLUSION: Syphilis is a re-emerging infection in Italy. Prevention strategies should include antenatal serological tests for all pregnant women and treatment for infected mothers.

Universal antenatal screening for group B streptococcus in Emilia-Romagna.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of severe infections in newborns. Intrapartum antibiotic chemoprophylaxis (IAP) reduces the rate of early-onset disease. The aim of this study is to determine the degree of clinicians' compliance with the suggested protocol for GBS prevention in Emilia-Romagna (Italy). METHODS: Characteristics of each delivery were prospectively recorded in the period between October 2005 to December 2005. Standardized pro-forma were used to collect data. RESULTS: Among 5118 babies, 7.2% (369) were preterm and 92.3% were born at term (4749). Antenatal screening was performed in 86.6% of women who delivered at term, of which 18.1% were GBS culture-positive. Information regarding culture site was available in 93.2% of women screened and recto-vaginal cultures were documented in 42.7%. IAP was administered to 28.7% of 3937 women at term who had either spontaneous delivery or emergency caesarean section. In this cohort, 15.9% were diagnosed GBS culture-positive, of which 92.6% received IAP. Prophylaxis was also administered to 8.4% (331) of women for no apparent reason. Compared with tertiary level hospitals, women delivering in primary/secondary hospitals were more likely to be both GBS screened (P < 0.0001; OR 3.04; CI 2.33-3.97) and to receive prophylaxis ≥4 hours before delivery (P = 0.0025; OR 1.57; CI 1.17-2.12). CONCLUSIONS: GBS screening was performed in >85% of women and >90% of culture-positive women received prophylaxis. However, there is a need to educate clinicians about protocol adherence, as most cultures were suboptimal and cases of unnecessary IAP were administered. The screening was more effective in hospitals with fewer deliveries.

Congenital syphilis like many years ago.

This case concerns a premature infant with typical signs of congenital syphilis born to an untreated foreign mother. Syphilis prevalence in pregnant women has been rising in Italy since the beginning of the 21st century, mainly due to immigration. A correct antenatal syphilis screening and consequent adequate therapy of pregnant woman are fundamental to prevent the neonatal infection.

Neonatal arterial iliac thrombosis in type-I protein C deficiency: a case report.

A male infant born by caesarean section at 38 weeks of gestational age (B.W. 4055 g; Apgar 9-10), in the first two hours of life his right leg became hypo-vascularized. Normal values of leukocytes, red cells, haematocrit, hemoglobin, platelets. C-Reactive Protein negative. Electrolytes and coagulation tests were normal. Normal vitamin K coagulation proteins levels. Serological tests for TORCH (IgM) and Parvovirus (IgG and IgM) were negative. Sonography showed a reduced blood flow in the iliac artery and reported a 1 cm long vessel thrombosis. From 8 hours of life we administered an intravenous infusion of unfractionated heparin (UFH) 75 UI/Kg for the first 10 minutes then 28 UI/Kg/h.On the 2nd day tests were performed to assess absence of inhibiting-clot factors. The dosage of homocysteine, protein S and antithrombin was normal. FV Leiden and antiphospholipid antibodies were negative. The mapping of G20210A prothrombin's gene resulted normal, whereas the concentration of Protein C was lower than normal: activity 46% (68-150%), antigen 35% (70-150%).The same deficiency was also found in the father. The mother showed normal concentrations. No episodes of thrombosis events were documented in the family. The intravenous unfractionated heparin (UFH) therapy was replaced after 64 hours by subcutaneous nadroparin 600 UI twice/day, which was stopped 5 days later when the vessel sonographic images were completely normal. During the hospitalization the infant didn't show bleeding. The child was followed-up yearly until 4 years of age: he was well and had a normal body and mental development.The final diagnosis is likely to be of a permanent protein C deficiency in heterozygous form. Our case is interesting because the first manifestation was an important thrombosis of large vessel that occurred within a few hours of life in absence of perinatal risk factors, as if it was a homozygous disease, but the patient had a heterozygotic form. In literature few cases are reported of heterozygous forms that became symptomatic, but only in old age.After a severe first manifestation, a normal and asymptomatic development is uncommon without new thrombotic episodes. In our patient the neonatal thrombosis was the sole event in his life.

Group B Streptococcus early-onset disease in Emilia-romagna: review after introduction of a screening-based approach.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections. Early-onset infections have decreased in recent years but, despite considerable efforts poured into prevention, cases continue to occur. OBJECTIVES: To analyze trends and identify determining factors for the persistence of the GBS infections. To evaluate the impact of antenatal screening and intrapartum chemoprophylaxis on the clinical presentation of the infection. METHODS: A prospective cohort, population-based study has been ongoing in Emilia-Romagna (Italy) since 2003. Invasive GBS infections, observed between 2003 and 2008 in infants aged < 7 days were analyzed. RESULTS: Among 214,120 live births, 61 early-infections were observed. Fourteen infants (23.0%) were born preterm. Among 47 infants who were delivered at term, 28 were born to mothers who had no risk factors and 7 were born to mothers who had none other than GBS colonization. Forty-one women at term had been screened prenatally; among them, only 10 were documented as GBS culture-positive.Disease severity was highest in infants at lower gestational ages, but most meningitis cases were observed in term infants born to mothers who were GBS culture-negative at screening.Nine newborns had culture-proven infection despite having received intrapartum antibiotics. They were born to mothers with > or =1 obstetrical risk factors and 5 mothers had been treated during labor with macrolides. CONCLUSION: Most infections presented in infants whose mothers had been screened as GBS culture-negative. Missed opportunities for prevention contributed more than prophylaxis failures to the early-onset disease burden.

Very low birth weight infants born to cytomegalovirus-seropositive mothers fed with their mother's milk: a prospective study.

OBJECTIVE: To assess the risk of post-natal cytomegalovirus (CMV) transmission to very low birth weight (VLBW) infants fed with their mother's fresh milk. STUDY DESIGN: Prospective, observational study of 80 VLBW infants and their 68 mothers. Infants' urine and their own mother's fresh breast milk were tested for CMV by means of culture tests once a week until discharge. CMV in infected milk and urine were genotyped. The clinical course, laboratory findings, and outcome of infants infected with CMV at 2 years of age are reported. RESULTS: Fifty-three mothers (78%) were CMV-seropositive at delivery. CMV was detected in the milk of 21 of 53 seropositive mothers (40%), and CMV was in the urine in 9 of 26 infants (35%) fed with CMV-positive milk. The same gN-genotype was found in milk and urine. Three infected infants <28 weeks gestational age (GA) had a mild sepsis-like illness. Five more infants had neutropenia, conjugated hyperbilirubinaemia, or both. Post-natal CMV infection occurred in 1 of 19 infants with a GA<28 weeks who were treated at birth with intravenous immunoglobulin versus 3 of 5 non-treated infants (P < .02). Symptomatic CMV infection was associated with bronchopulmonary dysplasia. No neurosensorial sequelae were found at 2 years of corrected age. CONCLUSIONS: CMV infection via fresh human milk is mild, self-limiting, and without sequelae. Very-low GA and pre-existing chronic diseases are associated with symptomatic infection.

Impact of a standardized hand hygiene program on the incidence of nosocomial infection in very low birth weight infants.

BACKGROUND: This study examined the effects of a standardized hand hygiene program on the rate of nosocomial infection (NI) in very low birth weight (VLBW) infants (birth weight < 1500 g) admitted to our neonatal intensive care unit (NICU). METHODS: We compared the rate of NI in VLBW infants in 2 separate periods. In the first period, staff were encouraged to perform handwashing using a plain fluid detergent (0.5% triclosan). In the second period, a standardized hand hygiene program was implemented using antimicrobial soap (4% chlorhexidine gluconate) and alcohol-based hand rubs. RESULTS: NI after 72 hours of life was detected in 16 of the 85 VLBW infants in the first period and in 5 of the 80 VLBW infants in the second period. The rate of central venous catheter colonization was significantly lower in the second period (5.8%) than in the first period (16.6%). CONCLUSION: In our NICU, the incidence of NI in VLBW infants was significantly reduced after the introduction of a standardized handwashing protocol. In our experience, a proper hand hygiene program can save approximately 10 NI episodes/year, at a cost of $10,000 per episode. Therefore, improving hand hygiene practice is a cost-effective program in the NICU.

Group B streptococcal infections in a northern region of Italy.

BACKGROUND: Group B streptococcus is a leading cause of neonatal bacterial infections. Despite adoption of preventive strategies, cases of infection continue to occur and there is concern that widespread antimicrobial prophylaxis might delay rather than prevent disease onset, increasing the rates of late-onset diseases. OBJECTIVES: The purpose of this study was to determine the incidence and clinical features of early- and late-onset group B streptococcus disease in a northern region of Italy where a screening-based approach had been proposed. METHODS: A population-based study was prospectively conducted in Emilia-Romagna, Italy. Infections that occurred during 2003-2005 in infants aged <3 months were analyzed. RESULTS: Among 112,933 live births, 56 cases of invasive disease (30 early- and 26 late-onset disease) were observed, giving an annual group B streptococcus disease incidence of 0.50 per 1000 live births. Eleven infants with early-onset disease showed no signs of illness or were mildly ill, whereas 19 had moderate-to-severe symptoms, and culture-proven meningitis was found in 2. Risk factors were detected in 12 women. Twenty-two mothers had antenatal screening; 5 were group B streptococcus colonized, but 17 were culture-negative. Prophylaxis was administered in 3 women. Three infants with late-onset diseases were mildly ill, whereas 23 had moderate-to-severe symptoms. Risk factors were found in 7 mothers. Late-onset diseases were clinically more severe than early-onset diseases; meningitis was diagnosed in 12 infants, and 4 of 26 died. CONCLUSIONS: The incidence of early-onset disease was low. Some early infections were still observed because of negative screening results or missed opportunity for prevention. Late-onset diseases accounted for most meningitis cases and deaths. Strict adherence to protocols and adoption of optimal culture methods would further improve prevention of early-onset disease, but the aim of future strategies should be the prevention of all invasive diseases.

A multicenter, randomized trial of prophylactic fluconazole in preterm neonates.

BACKGROUND: Invasive candida infections are a major cause of morbidity and mortality in preterm infants. We performed a multicenter, randomized, double-blind, placebo-controlled trial of fluconazole for the prevention of fungal colonization and infection in very-low-birth-weight neonates. METHODS: During a 15-month period, all neonates weighing less than 1500 g at birth from eight tertiary Italian neonatal intensive care units (322 infants) were randomly assigned to receive either fluconazole (at a dose of either 6 mg or 3 mg per kilogram of body weight) or placebo from birth until day 30 of life (day 45 for neonates weighing <1000 g at birth). We performed weekly surveillance cultures and systematic fungal susceptibility testing. RESULTS: Among infants receiving fluconazole, fungal colonization occurred in 9.8% in the 6-mg group and 7.7% in the 3-mg group, as compared with 29.2% in the placebo group (P<0.001 for both fluconazole groups vs. the placebo group). The incidence of invasive fungal infection was 2.7% in the 6-mg group and 3.8% in the 3-mg group, as compared with 13.2% in the placebo group (P=0.005 for the 6-mg group and P=0.02 for the 3-mg group vs. the placebo group). The use of fluconazole did not modify the relationship between colonization and the subsequent development of invasive fungal infection. Overall mortality was similar among groups, as was the incidence of cholestasis. No evidence for the emergence of resistant candida species was observed, but the study did not have substantial power to detect such an effect. CONCLUSIONS: Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).

Cranial ultrasound scanning and prediction of outcome in newborns with congenital cytomegalovirus infection.

OBJECTIVE: To report the accuracy of ultrasound scanning (US) in predicting neurodevelopmental and sensorineural outcome in patients with congenital cytomegalovirus (CMV) infection. STUDY DESIGN: Fifty-seven neonates with congenital CMV infection underwent brain US and were observed prospectively for motor skills, developmental quotient, and hearing function. RESULTS: Abnormal results on US were found in 12 of 57 neonates. US lesions were more frequent in newborns with clinical and laboratory signs of congenital CMV infection at birth (10/18) than in newborns who had no symptoms at birth (2/39; P < .001). At least 1 sequela developed in all neonates with symptoms who had abnormal US results, whereas none of the neonates with symptoms who had normal US results had long-term sequelae (P < .001). In the population without symptoms, sensorineural hearing loss developed in 3 of 37 (8.1%) neonates with normal US results, whereas severe sequelae developed in 1 of 2 neonates with abnormal US results. CONCLUSIONS: A good correlation was found between cerebral US abnormalities and the prediction of outcome in newborns who were congenitally infected with CMV and had symptoms at birth. US could be performed as the first neuroimaging study in these newborns. Data are insufficient to permit any suggestions for the population without symptoms.