- Email: [email protected]
The infant born to a mother with infectious disease risk
Early Human Development 89S4 (2013) S76–S78
The infant born to a mother with infectious disease risk Maria Grazia Capretti *, Giacomo Faldella UO Neonatologia, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Italy
1. Introduction Perinatal infections remain a significant cause of neonatal morbidity and mortality. Mother-to-child transmission (MTCT) can occur in utero (rubella, CMV, syphilis, Toxoplasma), intrapartum (HBV, HIV, group B streptococci, enteric gram-negative organisms, gonococci, chlamydiae) or during post-natal period (TBC, HIV, CMV) The microorganism type and the timing of infection influence the outcome that includes spontaneous abortion, intrauterine growth restriction, premature birth, stillbirth, congenital malformation and symptomatic or asymptomatic neonatal infection. 2. Hepatitis B virus As a conseguence of the universal immunization program started in 1990, currently in Italy the prevalence of women HBsAg-positive at delivery is 0.86%, with a significant difference between native and immigrant women (0.4% vs 2.5%). HBV vertical transmission occurs almost exclusively during the perinatal period. According to the Italian Health Ministry [1]. the serological screening for hepatitis B is mandatory and free of charge in pregnancy during the third trimester of pregnancy Women who haven’t been screened for HBV during pregnancy, must undergo the test urgently at delivery. Newborns of HBsAgpositive women must receive HB Immunoglobulins and HepB vaccine within 12–24 hours of life, a second dose of HepB vaccine after 4 weeks and additional doses at 3 and 11 months of life. Serologic tests (HBsAg and anti-HBs) are recommended 1–2 months after the vaccine protocol is completed to determine appropriate follow up. Hepatitis B vaccination prevents 85–95% of perinatal infections, while mothers with HBV replication have a high risk of MTCT: 10–32% of infants born to mothers with HBV DNA >108 copies/ml or HBeAg-positive are infected, despite neonatal active and passive immunizations. Breastfeeding does not increase the risk of infection in the infants if active and passive immunizations have been correctly provided. 3. Hepatitis C virus Serological screening for HCV is recommended, free of charge, during the last trimester of pregnancy, only for pregnant women at risk [1]. * Corresponding author. 0378-3782/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved.
HCV vertical transmission may occur in utero and/or during intrapartum period and currently there are no interventions to prevent MTCT. Transmission rate is 4–7% when the mother is viremic, with a higher probability when HCV-RNA is >106 copies/ml and when the mother presents HIV-coinfection (transmission rate: 40–60%). Vaginal delivery and breastfeeding do not increase the risk of infection. Congenital HCV infection is confirmed when HCV-RNA is detected in two subsequent serum samples of infant at least 3 months after birth or when anti-HCV IgG are positive at 18 months of life. Spontaneous clearance of HCV infection are reported in 30% of vertically infected infants. The remaining 70% of infected infants remains asymptomatic or with mild hepatitis during childhood but a small number of them can develop progressive liver disease. 4. HIV The Italian Health Ministry recommends HIV screening for all pregnant women in the first and third trimester of gestation, irrespective of risk factors, to ensure adequate management of pregnant infected women [1]. Without any intervention, the vertical transmission rate is 15– 30%. In Italy, after implementation of prevention measures, the overal transmission rate was 5.1% during 1996–1999, 2.2% during 2000–2005 and 1.0% during 2005–2010. In the same periods the proportion of immigrant woman among all the pregnant infected woman was 10%, 25.5% and 43.3%, respectively [2]. Thus, being born to an immigrant woman is a risk factor for perinatal HIV infection. Other major risk factors for MTCT are high maternal viral load, CD4+ count <200 cells/mm3 , symptoms of AIDS and acute HIV-infection during pregnancy. At present, according to CDC and AGOG recommendations: (A) Intravenous zidovudine is not longer recommended for mothers receiving antiretroviral drugs combination and who have HIV-RNA <400 copies/ml near delivery; (B) elective caesarean delivery is recommended only when maternal HIV-1 RNA level is >1000 copies/ml or it is unknown near delivery; (C) prophylaxis for 6 weeks with oral zidovudine (dosage appropriate for gestational age – GA – and birth weight) and proscription of breastfeeding are recommended for newborn; (D) for infants born to mothers with unknown HIV-status a rapid maternal testing after birth is recommended; if the test is positive the infant must promptly start prophylaxis with zidovudine and three doses of nevirapine [3].
M.G. Capretti, G. Faldella / Early Human Development 89S4 (2013) S76–S78
The guidelines (last updates July 2012) of US Antiretroviral Pregnancy Register are available from AIDSinfo website (http:// aidsinfo.nih.gov). Neonatal testing (HIV-1-DNA PCR) at birth is recommended only if the mother has not received antiviral drugs during pregnancy. All HIV-exposed infants should undergo tests at 14–21 days of age and, if negative, tests should be repeatead at 1–2 and 4–6 months. Any positive test should be twice repeated for confirmation and the infant should be promptly referred to a pediatric HIV specialist for antiretroviral treatment. The absence of HIV infection is confirmed by negative HIV-IgG test at 12–18 months of life.
S77
seroprevalence in pregnant women was 0.44% but it was 4.3% in women from Eastern Europe and 5.8% in women from CentralSouth America. The rate of congenital disease among exposed infants was 10.5% [6]. MTCT can occur at any GA. The stage of maternal disease is the most important risk factor for congenital syphilis. Untreated mother with primary or secondary stage has a transmission risk of 100%, early latent stage has a transmission risk of 40–83% and late latent stage of 2.5–10%. Maternal treatment with Penicillin >4 weeks before delivery set to zero the probability of neonatal infection. 8. Congenital cytomegalovirus infection
5. Congenital rubella syndrome Serological screening for rubella is recommended and free of charge in the first trimester of pregnancy and, if negative, it should be repeated at 14–18 weeks of GA [1]. In Italy the prevalence of rubella in 2005–2009 ranged from 1.8 to 83.3 per 1,000,000 population (vs the recommend 2015 target of <1 case/1,000,000 population) [4,5]; no cases of Congenital rubella syndrome (CRS) occurred in 2005–2008, but 6 were reported in 2009. Rubella infection during pregnancy can be symptomatic or inapparent. Suspicion of rubella during pregnancy requires confirmation testing (IgG/IgM test, IgG avidity test, RT-PCR of blood or other biologic fluid). When maternal infection occurs in the first 10 weeks of gestation the rate of infection is 90%; afterwards it is 67% at 11–14 weeks, 40% at 15–30 weeks, 60% at 31–36 weeks and 100% near term. The rate of fetal damage is 90% in the first 10 weeks, 33% at 11–12 weeks, 10% at 13–18 weeks; after 18 weeks of GA only sporadic hearing defects have been reported. Fetal infection can result in miscarriage, stillbirth and CRS Congenital infection is confirmed by positive RT-PCR or virus isolation in pharyngeal swab, urine, blood and cerebrospinal liquor and/or positive IgM in the first month of life, and/or IgG persistence; the disappearance of IgG after 6 months of life confirm the absence of congenital infection. In Italy CRS notification is statutory since 2005. Pregnant women found to be susceptible should be vaccinated after delivery. 6. Congenital toxoplasmosis Serological screening for Toxoplasma gondii (Tg) is recommended and free of charge in the first trimester of pregnancy and, if negative, it should be repeated every 4–6 weeks until delivery [1]. Primary infection is mostly asymptomatic in pregnant women, but can cause a wide spectrum of fetal/neonatal damage. In our experience, the prenatal screening during the 2009–2011 period showed a seroprevalence rate of 22.3%, with a significantly higher rate among non-native women than among native women (32.8% vs 19.1%). The rate of primary Tg-infection during pregnancy was 0.77%; immigrant women were more likely to be infected during pregnancy than Italian women. The rate of congenital disease was 0.06%. Transmission rate is <2% in the first 10 weeks of gestation, and progressively increases thereafter to 50% at 22–29 weeks and 60–80% at 31–38 weeks of GA. The risk of neonatal symptomatic disease is 80% when the maternal infection occurs in the first trimester, and after decreases to 20% at 30 weeks and 6% near term. 7. Congenital syphilis Serological screening for Treponema pallidum (TPHA and VDRL or RPR) is recommended and free of charge during the first and the third trimester of pregnancy [1]. In our experience (2000–2006 period), the overall syphilis
Screening for cytomegalovirus during pregnancy is not recommended [1], given the lack of interventions to reduce MTCT. The rate of congenital CMV infection is 0.3–2% of all liveborn newborns. Transmission rate during primary infection in preconceptional period is 0–16.7%, in periconception period is 4.6–38.5%, in the first trimester is 30.1–42.2%, in the second trimester is 35.9–43.5% in the third trimester is 42.9–72.2%. The rate of symptomatic infection among infants born to mothers with primary infection during the first trimester of gestation is 36%, during the second trimester is 17%, and no symptoms are present if the mother became infected in the last trimester of gestation [7]. MTCT of CMV is more frequent during primary than secondary maternal infection (30–40% vs 1–3%). Management of women with Toxoplasma/syphilis/CMV infection during pregnancy and their infants are available from SIN websiteguidelines section (http://www.neonatologia.it). 9. Congenital varicella and neonatal chickenpox (VZV) In 1996–2003 in Italy the reported rate of VZV-seronegativity among women of childbearing age was 12.6%. VZV infection during pregnancy can cause abortion, premature labor, and congenital varicella syndrome (CVS) that include skin scars, limb defects, chorioretinitis, cataracts, microcephaly, cerebral atrophy, mental retardation. CSV incidence rate is 0.4% when maternal infection occurs between 0 and 12 weeks of GA and 2% if infection occurs between 13 and 20 weeks; the risk of birth defects is neglectable after 20 weeks of GA, but asymptomatic congenital disease occurs in 10–25% and infantile zooster in 0.8–1.7% of cases. Congenital infection is confirmed by positive VZV-PCR or virus isolation in blood and/or cerebrospinal liquor and/or positive IgM in the first month of life, and/or IgG positivity after 6 months of life. When maternal rash appears between 21 and 6 days before delivery, a mild form of neonatal chickenpox may develop (20–50% of exposed newborns, no mortality). When maternal rash appears in the peripartum period (5 days before and 2 days after delivery) a severe form of neonatal chickenpox including hemorrhagic disease, pneumonia, meningoencephalitis may develop (20–50% of exposed newborns, 3–20% mortality). It is recommended to administer VZ immunoglobulins to newborn when maternal rash occurs in the peripartum period. Acyclovir treatment is recommended when newborn develops chickenpox. 10. Early onset sepsis (EOS) EOS are associated with intrapartum exposure to the pathogens organisms, acquired in utero or during labor or delivery. Risk factors for EOS include prematurity, prolonged rupture of membranes >18 h (PROM), maternal colonization with group B Streptococcus (GBS) and maternal chorioamnionitis. This latter condition can remain clinically silent in the mother and can be diagnosed by
M.G. Capretti, G. Faldella / Early Human Development 89S4 (2013) S76–S78
S78
histological abnormalities of the placenta; severe but rare cases of chorioamnionitis may be symptomatic (maternal fever >38°C, maternal tachycardia, leukocytosis, elevated C-reactive protein – CRP, uterine fundal tenderness, vaginal discharge, fetal tachycardia). According to the 2012 statement of the AAP Committee on Fetus and Newborn, asymptomatic at term neonates with suspected sepsis or inadequate intrapartum antibiotic prophylaxis should receive CRP and WBC count evaluation and, if abnormal, blood culture and broad spectrum antibiotics (ampicillin and aminoglycoside). Then, if the newborn remains well and the blood culture is negative, he can be discharged at 48 hours [8]. This approach has several critical points as it increases the number of newborns undergoing diagnostic tests and admitted to the Neonatology ward to receive broad spectrum antibiotics with potential risk of selection of antibioticresistant organisms. Conflict of interest The authors have no conflict of interest to declare. References [1] Ministero della Salute, Istituto Superiore di Sanità, CeVEAS: Sistema Nazionale per le Linee Guida: Gravidanza fisiologica aggiornamento 2011, http://www. snlg-iss.it
[2] Chiappini E, Galli L, Giacquinto C et al.: Risk of Perinatal HIV infection in infant born in Italy from immigrant mothers. CID, 2011:53(3): 310–313. [3] Nielsen-Saines K, Watts H., Veloso VG et al.: Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. N Engl J Med 2012; 366:2368– 79. [4] World Health Organization Regional Office for Europe. Surveillance Guidelines for Measles, Rubella and Congenital Rubella Syndrome in the WHO European region. Update December 2012 [5] Center for Disease Control and Prevention: Manual for the Surveillance of Vaccine-Preventable Diseases (5th edition 2012); chapter 15: congenital rubella syndrome. Available on the internet at: http://www.cdc.gov/vaccines/pubs/ surv-manual/. [6] Tridapalli E, Capretti MG, Sambri V et al: Prenatal syphilis infection is a possibile cause of preterm delivery among immigrant women from eastern Europe. Sex Transm Infect 2007; 83(2): 102–5. [7] Enders G, Daiminger A, Bader U et al: Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J Clin Virol 2011;53(3):244–6. [8] Polin RA and the Committee on Fetus and Newborn: Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012; 129(5): 1006–15.
The infant born to a mother with infectious disease risk Maria Grazia Capretti *, Giacomo Faldella UO Neonatologia, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Italy
1. Introduction Perinatal infections remain a significant cause of neonatal morbidity and mortality. Mother-to-child transmission (MTCT) can occur in utero (rubella, CMV, syphilis, Toxoplasma), intrapartum (HBV, HIV, group B streptococci, enteric gram-negative organisms, gonococci, chlamydiae) or during post-natal period (TBC, HIV, CMV) The microorganism type and the timing of infection influence the outcome that includes spontaneous abortion, intrauterine growth restriction, premature birth, stillbirth, congenital malformation and symptomatic or asymptomatic neonatal infection. 2. Hepatitis B virus As a conseguence of the universal immunization program started in 1990, currently in Italy the prevalence of women HBsAg-positive at delivery is 0.86%, with a significant difference between native and immigrant women (0.4% vs 2.5%). HBV vertical transmission occurs almost exclusively during the perinatal period. According to the Italian Health Ministry [1]. the serological screening for hepatitis B is mandatory and free of charge in pregnancy during the third trimester of pregnancy Women who haven’t been screened for HBV during pregnancy, must undergo the test urgently at delivery. Newborns of HBsAgpositive women must receive HB Immunoglobulins and HepB vaccine within 12–24 hours of life, a second dose of HepB vaccine after 4 weeks and additional doses at 3 and 11 months of life. Serologic tests (HBsAg and anti-HBs) are recommended 1–2 months after the vaccine protocol is completed to determine appropriate follow up. Hepatitis B vaccination prevents 85–95% of perinatal infections, while mothers with HBV replication have a high risk of MTCT: 10–32% of infants born to mothers with HBV DNA >108 copies/ml or HBeAg-positive are infected, despite neonatal active and passive immunizations. Breastfeeding does not increase the risk of infection in the infants if active and passive immunizations have been correctly provided. 3. Hepatitis C virus Serological screening for HCV is recommended, free of charge, during the last trimester of pregnancy, only for pregnant women at risk [1]. * Corresponding author. 0378-3782/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved.
HCV vertical transmission may occur in utero and/or during intrapartum period and currently there are no interventions to prevent MTCT. Transmission rate is 4–7% when the mother is viremic, with a higher probability when HCV-RNA is >106 copies/ml and when the mother presents HIV-coinfection (transmission rate: 40–60%). Vaginal delivery and breastfeeding do not increase the risk of infection. Congenital HCV infection is confirmed when HCV-RNA is detected in two subsequent serum samples of infant at least 3 months after birth or when anti-HCV IgG are positive at 18 months of life. Spontaneous clearance of HCV infection are reported in 30% of vertically infected infants. The remaining 70% of infected infants remains asymptomatic or with mild hepatitis during childhood but a small number of them can develop progressive liver disease. 4. HIV The Italian Health Ministry recommends HIV screening for all pregnant women in the first and third trimester of gestation, irrespective of risk factors, to ensure adequate management of pregnant infected women [1]. Without any intervention, the vertical transmission rate is 15– 30%. In Italy, after implementation of prevention measures, the overal transmission rate was 5.1% during 1996–1999, 2.2% during 2000–2005 and 1.0% during 2005–2010. In the same periods the proportion of immigrant woman among all the pregnant infected woman was 10%, 25.5% and 43.3%, respectively [2]. Thus, being born to an immigrant woman is a risk factor for perinatal HIV infection. Other major risk factors for MTCT are high maternal viral load, CD4+ count <200 cells/mm3 , symptoms of AIDS and acute HIV-infection during pregnancy. At present, according to CDC and AGOG recommendations: (A) Intravenous zidovudine is not longer recommended for mothers receiving antiretroviral drugs combination and who have HIV-RNA <400 copies/ml near delivery; (B) elective caesarean delivery is recommended only when maternal HIV-1 RNA level is >1000 copies/ml or it is unknown near delivery; (C) prophylaxis for 6 weeks with oral zidovudine (dosage appropriate for gestational age – GA – and birth weight) and proscription of breastfeeding are recommended for newborn; (D) for infants born to mothers with unknown HIV-status a rapid maternal testing after birth is recommended; if the test is positive the infant must promptly start prophylaxis with zidovudine and three doses of nevirapine [3].
M.G. Capretti, G. Faldella / Early Human Development 89S4 (2013) S76–S78
The guidelines (last updates July 2012) of US Antiretroviral Pregnancy Register are available from AIDSinfo website (http:// aidsinfo.nih.gov). Neonatal testing (HIV-1-DNA PCR) at birth is recommended only if the mother has not received antiviral drugs during pregnancy. All HIV-exposed infants should undergo tests at 14–21 days of age and, if negative, tests should be repeatead at 1–2 and 4–6 months. Any positive test should be twice repeated for confirmation and the infant should be promptly referred to a pediatric HIV specialist for antiretroviral treatment. The absence of HIV infection is confirmed by negative HIV-IgG test at 12–18 months of life.
S77
seroprevalence in pregnant women was 0.44% but it was 4.3% in women from Eastern Europe and 5.8% in women from CentralSouth America. The rate of congenital disease among exposed infants was 10.5% [6]. MTCT can occur at any GA. The stage of maternal disease is the most important risk factor for congenital syphilis. Untreated mother with primary or secondary stage has a transmission risk of 100%, early latent stage has a transmission risk of 40–83% and late latent stage of 2.5–10%. Maternal treatment with Penicillin >4 weeks before delivery set to zero the probability of neonatal infection. 8. Congenital cytomegalovirus infection
5. Congenital rubella syndrome Serological screening for rubella is recommended and free of charge in the first trimester of pregnancy and, if negative, it should be repeated at 14–18 weeks of GA [1]. In Italy the prevalence of rubella in 2005–2009 ranged from 1.8 to 83.3 per 1,000,000 population (vs the recommend 2015 target of <1 case/1,000,000 population) [4,5]; no cases of Congenital rubella syndrome (CRS) occurred in 2005–2008, but 6 were reported in 2009. Rubella infection during pregnancy can be symptomatic or inapparent. Suspicion of rubella during pregnancy requires confirmation testing (IgG/IgM test, IgG avidity test, RT-PCR of blood or other biologic fluid). When maternal infection occurs in the first 10 weeks of gestation the rate of infection is 90%; afterwards it is 67% at 11–14 weeks, 40% at 15–30 weeks, 60% at 31–36 weeks and 100% near term. The rate of fetal damage is 90% in the first 10 weeks, 33% at 11–12 weeks, 10% at 13–18 weeks; after 18 weeks of GA only sporadic hearing defects have been reported. Fetal infection can result in miscarriage, stillbirth and CRS Congenital infection is confirmed by positive RT-PCR or virus isolation in pharyngeal swab, urine, blood and cerebrospinal liquor and/or positive IgM in the first month of life, and/or IgG persistence; the disappearance of IgG after 6 months of life confirm the absence of congenital infection. In Italy CRS notification is statutory since 2005. Pregnant women found to be susceptible should be vaccinated after delivery. 6. Congenital toxoplasmosis Serological screening for Toxoplasma gondii (Tg) is recommended and free of charge in the first trimester of pregnancy and, if negative, it should be repeated every 4–6 weeks until delivery [1]. Primary infection is mostly asymptomatic in pregnant women, but can cause a wide spectrum of fetal/neonatal damage. In our experience, the prenatal screening during the 2009–2011 period showed a seroprevalence rate of 22.3%, with a significantly higher rate among non-native women than among native women (32.8% vs 19.1%). The rate of primary Tg-infection during pregnancy was 0.77%; immigrant women were more likely to be infected during pregnancy than Italian women. The rate of congenital disease was 0.06%. Transmission rate is <2% in the first 10 weeks of gestation, and progressively increases thereafter to 50% at 22–29 weeks and 60–80% at 31–38 weeks of GA. The risk of neonatal symptomatic disease is 80% when the maternal infection occurs in the first trimester, and after decreases to 20% at 30 weeks and 6% near term. 7. Congenital syphilis Serological screening for Treponema pallidum (TPHA and VDRL or RPR) is recommended and free of charge during the first and the third trimester of pregnancy [1]. In our experience (2000–2006 period), the overall syphilis
Screening for cytomegalovirus during pregnancy is not recommended [1], given the lack of interventions to reduce MTCT. The rate of congenital CMV infection is 0.3–2% of all liveborn newborns. Transmission rate during primary infection in preconceptional period is 0–16.7%, in periconception period is 4.6–38.5%, in the first trimester is 30.1–42.2%, in the second trimester is 35.9–43.5% in the third trimester is 42.9–72.2%. The rate of symptomatic infection among infants born to mothers with primary infection during the first trimester of gestation is 36%, during the second trimester is 17%, and no symptoms are present if the mother became infected in the last trimester of gestation [7]. MTCT of CMV is more frequent during primary than secondary maternal infection (30–40% vs 1–3%). Management of women with Toxoplasma/syphilis/CMV infection during pregnancy and their infants are available from SIN websiteguidelines section (http://www.neonatologia.it). 9. Congenital varicella and neonatal chickenpox (VZV) In 1996–2003 in Italy the reported rate of VZV-seronegativity among women of childbearing age was 12.6%. VZV infection during pregnancy can cause abortion, premature labor, and congenital varicella syndrome (CVS) that include skin scars, limb defects, chorioretinitis, cataracts, microcephaly, cerebral atrophy, mental retardation. CSV incidence rate is 0.4% when maternal infection occurs between 0 and 12 weeks of GA and 2% if infection occurs between 13 and 20 weeks; the risk of birth defects is neglectable after 20 weeks of GA, but asymptomatic congenital disease occurs in 10–25% and infantile zooster in 0.8–1.7% of cases. Congenital infection is confirmed by positive VZV-PCR or virus isolation in blood and/or cerebrospinal liquor and/or positive IgM in the first month of life, and/or IgG positivity after 6 months of life. When maternal rash appears between 21 and 6 days before delivery, a mild form of neonatal chickenpox may develop (20–50% of exposed newborns, no mortality). When maternal rash appears in the peripartum period (5 days before and 2 days after delivery) a severe form of neonatal chickenpox including hemorrhagic disease, pneumonia, meningoencephalitis may develop (20–50% of exposed newborns, 3–20% mortality). It is recommended to administer VZ immunoglobulins to newborn when maternal rash occurs in the peripartum period. Acyclovir treatment is recommended when newborn develops chickenpox. 10. Early onset sepsis (EOS) EOS are associated with intrapartum exposure to the pathogens organisms, acquired in utero or during labor or delivery. Risk factors for EOS include prematurity, prolonged rupture of membranes >18 h (PROM), maternal colonization with group B Streptococcus (GBS) and maternal chorioamnionitis. This latter condition can remain clinically silent in the mother and can be diagnosed by
M.G. Capretti, G. Faldella / Early Human Development 89S4 (2013) S76–S78
S78
histological abnormalities of the placenta; severe but rare cases of chorioamnionitis may be symptomatic (maternal fever >38°C, maternal tachycardia, leukocytosis, elevated C-reactive protein – CRP, uterine fundal tenderness, vaginal discharge, fetal tachycardia). According to the 2012 statement of the AAP Committee on Fetus and Newborn, asymptomatic at term neonates with suspected sepsis or inadequate intrapartum antibiotic prophylaxis should receive CRP and WBC count evaluation and, if abnormal, blood culture and broad spectrum antibiotics (ampicillin and aminoglycoside). Then, if the newborn remains well and the blood culture is negative, he can be discharged at 48 hours [8]. This approach has several critical points as it increases the number of newborns undergoing diagnostic tests and admitted to the Neonatology ward to receive broad spectrum antibiotics with potential risk of selection of antibioticresistant organisms. Conflict of interest The authors have no conflict of interest to declare. References [1] Ministero della Salute, Istituto Superiore di Sanità, CeVEAS: Sistema Nazionale per le Linee Guida: Gravidanza fisiologica aggiornamento 2011, http://www. snlg-iss.it
[2] Chiappini E, Galli L, Giacquinto C et al.: Risk of Perinatal HIV infection in infant born in Italy from immigrant mothers. CID, 2011:53(3): 310–313. [3] Nielsen-Saines K, Watts H., Veloso VG et al.: Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. N Engl J Med 2012; 366:2368– 79. [4] World Health Organization Regional Office for Europe. Surveillance Guidelines for Measles, Rubella and Congenital Rubella Syndrome in the WHO European region. Update December 2012 [5] Center for Disease Control and Prevention: Manual for the Surveillance of Vaccine-Preventable Diseases (5th edition 2012); chapter 15: congenital rubella syndrome. Available on the internet at: http://www.cdc.gov/vaccines/pubs/ surv-manual/. [6] Tridapalli E, Capretti MG, Sambri V et al: Prenatal syphilis infection is a possibile cause of preterm delivery among immigrant women from eastern Europe. Sex Transm Infect 2007; 83(2): 102–5. [7] Enders G, Daiminger A, Bader U et al: Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J Clin Virol 2011;53(3):244–6. [8] Polin RA and the Committee on Fetus and Newborn: Management of neonates with suspected or proven early-onset bacterial sepsis. Pediatrics 2012; 129(5): 1006–15.