Update in Pediatric Diagnostic Microbiology.

Infants and young children are uniquely susceptible to primary viral and bacterial infections, predisposing them to responses of greater frequency and severity than in adults. Etiologies and manifestations of infections in pediatric patients are often different than those in adults. It can be challenging for clinical laboratories to implement appropriate microbiologic methods for rapid and accurate diagnoses in this population. Laboratorians should be cognizant of the distinctive features of children to provide comprehensive pediatric clinical microbiology services. This article discusses laboratory aspects of several clinically significant pediatric pathogens that cause severe harm to patients and impact public health responses.

Performance of a Multiplex Nested Polymerase Chain Reaction in Detecting 7 Pathogens Containing DNA in Their Genomes Associated With Congenital Infections.

CONTEXT.­: Infections are the leading cause of perinatal and infant mortality in low-income and low-resource countries, which have a higher prevalence of infections. Definitive diagnosis of congenital and perinatal infections is largely dependent upon the results of laboratory tests. OBJECTIVE.­: To develop a multiplex nested polymerase chain reaction (PCR) technique for the simultaneous detection of 7 pathogens containing DNA in their genomes in suspected cases of congenital infection. DESIGN.­: Eligible participants were pregnant women with positive immunoglobulin M antibodies raised to one of the pathogens in the prenatal serologic screening, associated or not with fetal ultrasound abnormalities or positive fetal serology. Neonates whose mothers did not attend prenatal care were included when they presented with symptomatology and laboratory parameters suggestive of infection. The detection rate of the multiplex nested PCR was compared with maternal, fetal, and neonatal serology, as well as placental immunohistochemistry and noncommercial amplifications. RESULTS.­: Of 161 suspected cases, the multiplex nested PCR detected 60 (37.3%), whereas the tests available in hospital laboratories detected 13 of 60 (21.7%) of the cases detected by the multiplex nested PCR, demonstrating a 4.6 times higher detection rate for the multiplex nested PCR (Fisher exact test, P < .001). Positive amplifications were to Toxoplasma gondii (32 cases), cytomegalovirus (14 cases), parvovirus B19 (5 cases), and adenovirus (5 cases). In 4 cases, 2 pathogens were simultaneously detected. All types of biological matrices were suitable for amplification. Sequencing of multiplex nested PCR products confirmed the molecular findings. CONCLUSIONS.­: The multiplex nested PCR significantly increased the number of diagnosed congenital infections. Given the scarcity of DNA recovered from amniotic fluid and some neonatal samples, this multiplex nested PCR allows the simultaneous detection of 7 pathogens associated with congenital infections in a reliable, faster, cost-effective, and more sensitive way.

Congenital infections as contributors to the onset of diabetes in children: A longitudinal study in the United States, 2001-2017.

BACKGROUND: Maternal infections during pregnancy, particularly with rubella virus, were reported to increase the risk of diabetes in children. Widespread vaccination has decreased the number of infants with congenital rubella syndrome in the United States, although it remains a problem in developing countries. Because vaccine hesitancy has recently increased, we investigated the association between congenital infections with subsequent diabetes risk in children in the United States. METHODS: Using data from a nationwide private health insurer for years 2001-2017, 1 475 587 infants were followed for an average of 3.9 years (maximum 16.5 years). Information was obtained regarding congenital infections (rubella, cytomegalovirus, other congenital infections) and perinatal infections, as well as for the development of diabetes mellitus and diabetic ketoacidosis. RESULTS: There were 781 infants with congenital infections and 73 974 with perinatal infections. Diabetes developed in 3334 children. The odds of developing diabetes for infants with congenital rubella infection were 12-fold greater (P = .013) and, for infants with congenital cytomegalovirus infection, were 4-fold greater (P = .011) than infants without congenital or perinatal infection. Infants with other congenital infections had 3-fold greater odds of developing diabetes (P = .044). Results were similar for diabetes ketoacidosis. Infants with other perinatal infections had 49% greater odds of developing diabetes during the follow-up period (P < .001). CONCLUSION: Congenital and other perinatal infections are associated with elevated risks of developing diabetes mellitus during childhood. Vaccination for rubella remains an important preventive action to reduce the incidence of diabetes in children.

Viral Infections and the Neonatal Brain.

This review includes the congenital infections best known by the acronym TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), as well as Zika virus infection and perinatally acquired infections (enterovirus, parechovirus, rotavirus, parvovirus). Congenital infections are due to pathogens that can cross the placenta and are more likely to injure the brain when the infection occurs early in pregnancy. There are many similarities, with regards to brain lesions, for congenital Zika syndrome and congenital cytomegalovirus infection. Perinatally acquired viral infections tend to injure the white matter, with cystic evolution being more likely in the (late) preterm infant compared to the full-term infant. Congenital and perinatally acquired viral infections can be associated with adverse neurological outcomes. Prevention is important, especially as therapeutic options are limited. In this review both congenital as well as perinatally acquired viral infections will be discussed with a focus on neuro-imaging findings.

Congenital and perinatal infections.

Congenital and perinatal infections represent major causes of permanent disability among children worldwide. Linked together by the acronym TORCH, denoting Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus, congenital infections can result from only a modest number of human pathogens that cross the placenta and infect the fetus. Although congenital rubella syndrome has been eliminated in the Americas by immunization, several pathogens discussed in this chapter cannot currently be prevented by vaccines or effectively treated with the available antimicrobial drugs. Due to the immaturity of the immune system, newborn infants are at risk for postnatally acquired infections with certain viruses and several bacteria. This chapter summarizes the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prevention of selected pathogens that can damage the developing nervous system. As emphasized by the persisting challenges of preventing congenital cytomegalovirus infection and the emergence of severe brain damage associated with congenital Zika syndrome, these pathogens remain important causes of cerebral palsy, epilepsy, and intellectual disability.

Perinatal and long-term outcomes in fetuses diagnosed with isolated unilateral ventriculomegaly: systematic review and meta-analysis.

OBJECTIVES: The majority of studies on fetal ventriculomegaly have focused on the perinatal and long-term outcomes in fetuses with an antenatal diagnosis of bilateral ventriculomegaly. The aim of this study was to undertake a systematic review and meta-analysis to quantify the perinatal and long-term outcomes in fetuses diagnosed in the second or third trimester of pregnancy with isolated unilateral ventriculomegaly. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched electronically. Outcomes investigated included incidence of aneuploidy, congenital infection, progression of ventriculomegaly, associated brain and extracerebral abnormalities in the apparently isolated cases and neurodevelopmental delay in both apparently and truly isolated cases. Sensitivity analysis was performed according to whether the ventriculomegaly was mild/moderate (atrial width < 15 mm) or severe (atrial width ≥ 15 mm). Reference lists within relevant articles and reviews were hand-searched for additional reports. Cohort and case-control studies were included. Meta-analysis of proportions was used, and between-study heterogeneity was assessed using the I2 test. RESULTS: The search yielded 2053 citations. The full text was retrieved for 202, and 11 studies were included in the systematic review. In fetuses with apparently isolated unilateral ventriculomegaly, no chromosomal abnormalities were identified and the pooled prevalence of congenital infection was 8.2% (95% CI, 3.6-14.5%). The pooled prevalence of additional brain abnormalities detected prenatally and postnatally by magnetic resonance imaging was 5.1% (95% CI, 0.2-16.1%) and 6.4% (95% CI, 0.3-19.4%), respectively. The pooled prevalence of abnormal neurodevelopment was 5.9% (95% CI, 2.2-11.2%) in apparently isolated cases with an atrial width of < 15 mm, and it was 7.0% (95% CI, 3.2-12.2%) in fetuses with truly isolated unilateral ventriculomegaly. Most cases with apparently isolated ventriculomegaly were classified as mild/moderate (93.5%) and therefore the outcomes in this group were similar to those in the whole cohort of apparently isolated ventriculomegaly. CONCLUSIONS: The prevalence of aneuploidy, congenital infection and neurodevelopmental delay in fetuses with a prenatal diagnosis of isolated unilateral ventriculomegaly is likely to be low. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Congenital Infections in Neonates of Women With Liver or Kidney Transplants.

BACKGROUND: Immunosuppressive therapy is associated with an increased risk of pregnancy complications and may have adverse effects for the newborn. The aim of this study was to determine the frequency and the type of early congenital infections and to assess typical markers of infections in neonates of liver and kidney recipients. METHODS: A retrospective analysis of 71 neonates born to either liver (39 cases) or kidney transplanted women (32 cases) was conducted. The rate and the type of newborns' infections as well as laboratory and bacteriologic markers of infections were analyzed. RESULTS: There was no significant difference in the frequency of congenital infections between the LT and KT groups (8 vs 7 cases; P = .879).). The rate of infections was not significantly higher in both groups compared with the general population. Infections were detected in 23.9%, 13.6%, and 26.6% of neonates born to mothers using tacrolimus, cyclosporine, and azathioprine respectively. No significant differences in white blood count or levels of neutrocytes and lymphocytes were observed between the groups. No abnormalities in white blood smear, but 1 case of leukopenia in the kidney transplant group, were detected. CONCLUSIONS: The rate of congenital infections in neonates of allograft recipients is not significantly higher than in the general population. Immunosuppressive regimens with azathioprine seem to carry the greatest risk, it is a little lower in the tacrolimus group, and cyclosporine-based regimens have the lowest risk of congenital infections. Differences were not statistically significant. Prenatal exposure to immunosuppressive agents seems not to be associated with any hematologic disturbances in white blood count and white blood smear.

Criptococosis congénita en un neonato expuesto a VIH: presentación de un caso / Congenital cryptococcosis in a newborn exposed to HIV: A case report

La criptococosis puede afectar niños de todas las edades, especialmente aquellos inmunocomprometidos. Usualmente se adquiere a través de la inhalación de esporas del medio ambiente, aunque existen otras formas de transmisión. Describimos un caso de criptococosis congénita adquirido de una madre con síndrome de inmunodeficiencia adquirida (SIDA) y tratado en forma exitosa con combinación de antimicoticos.

Cryptococcosis may affect children of all ages, specially those who are inmunocompromised. It is usually acquired from the inhalation of environmental spores, although other sources of transmission exist. We describe a case of congenital cryptococcosis transmitted from a mother with acquired immunodeficiency syndrome (AIDS), which was successfully treated with combination antifungal agents.

Utilidad de la reacción en cadena de la polimerasa en el diagnóstico de infección congénita por citomegalovirus: a propósito de un caso de meningitis aséptica / Polymerase chain reaction in the diagnosis of congenital infection cytomegalovirus: A purpose of a case of aseptic meningitis

Se informa del caso de un recién nacido que presentó trombocitopenia, hematuria y proteinuria. En el líquido cefalorraquídeo tenía aumento de proteínas y leucocitos, VDRL no reactiva. La madre tenía historia de sífilis gestacional. Las determinaciones de IgM para citomegalovirus, rubéola, Toxoplasma , herpes i y ii fueron negativas por lo que se consideró caso de sífilis congénita con compromiso de sistema nervioso central. Por persistir la trombocitopenia después del tratamiento, se tomó muestra de sangre para PCR para citomegalovirus, encontrándose 181.171 copias/ml. Se dio tratamiento con ganciclovir intravenoso 12 mg/kg de peso durante 21 días y solución al 10% de inmunoglobulina humana hiperinmune para citomegalovirus administrada así: 4 ml/kg de peso los días 0, 4 y 8, seguido de 2 ml/kg de peso los días 12 y 16. La evolución fue satisfactoria. Se evidenció la utilidad de PCR en el diagnóstico de infección congénita por citomegalovirus.

We report a case of a newborn with persistent thrombocytopenia, hematuria, proteinuria, as well as increased proteins and leukocytes in cerebrospinal fluid, with a non-reactive VDRL. His mother had history of gestational syphilis. IgM levels against cytomegalovirus, rubella, toxoplasma, herpes i and ii were negative, which led to suspicion of congenital syphilis with central nervous system involvement. A polymerase chain reaction test for cytomegalovirus showed 181.171 copies/ml in serum. The newborn was treated with intravenous ganciclovir at 12 mg per kg body weight for 21 days and a 10% solution of human cytomegalovirus hyperimmune immunoglobulin, administered as follows: 4 ml per kg body weight on days 0, 4 and 8, followed by 2 ml per kg weight on days 12 and 16. The clinical outcome was satisfactory. This study highlights the usefulness of PCR for the diagnosis of congenital CMV infection.

[Vaccination of premature infants, a population at high risk of infection]. / Les enfants prématurés, une population à haut risque d'infection qui doit être protégée par la vaccination.

The incidence of prematurity has steadily increased in Belgium these last years, reaching 7,9 % in 2010. Infections remain for these infants an important cause of morbidity and mortality during their hospitalization in the neonatal intensive care units as well as during their first months of life in the community. Despite the immaturity of their immune system, their ability to develop a protective immune response to most vaccines has been established. Instable very low birth weight prematures are at risk cardio- respiratory incidents after vaccine administration, but these incidents are transient and without consequences if they are monitored during and after vaccination. This paper reviews the current recommendations on the immunization of the premature infants.

The current and future roles of neonatal infection surveillance programmes in combating antimicrobial resistance.

Neonatal sepsis is an important cause of morbidity and mortality, particularly in premature or low birth weight babies. Hospital-acquired blood stream infections represent a significant and largely preventable cause of disease in this population. Neonatal units have been identified as a common site for the development and transmission of antimicrobial-resistant pathogens, a significant issue in modern medicine. Neonatal surveillance programmes collect prospective data on infection rates and may be used to optimise therapy, benchmark practice and develop quality improvement programmes. Despite this, the number of networks is relatively few and these are largely concentrated in resource-rich nations. Furthermore, surveillance definitions may vary between programmes impairing our ability to draw comparisons between them. Better harmonisation is required between networks to ensure that they achieve their potential as a valuable tool for benchmarking of hospital-acquired infection rates between units.

[Prevalence of congenital and perinatal infection in HIV positive pregnant in Belo Horizonte metropolitan region]. / Prevalência de infecções congênitas e perinatais em gestantes HIV positivas da região metropolitana de Belo Horizonte.

PURPOSE: To evaluate the prevalence of toxoplasmosis, rubella, cytomegalovirus, hepatitis B&C and syphilis (Torchs) in a cohort pregnant women and to identify the sociodemographic, clinical and laboratory factors. METHODS: A total of 1,573 HIV-infected pregnant women from a Brazilian metropolitan region were studied between 1998 and 2013. The results of serological tests were available for 704 (44.8%) pregnant women. Pregnant women were considered to be Torchs positive (Gtp) when they had positive results for at least one of these infections, and to be Torchs negative (Gtn) when they had negative results for all of them. Maternal covariables were: age, marital status, educational level, time and mode of infection, CD4 lymphocyte count, viral load at delivery, and use of antiretroviral therapy (ARV). Neonatal covariables were: HIV infection, prematurity, low birth weight, neonatal complications, abortion and neonatal death. Odds ratios with 95% confidence interval were used to quantify the association between maternal and neonatal variables and the presence of Torchs. RESULTS: Among 704 pregnant women, 70 (9.9%; 95%CI 7.8-12.4) had positive serological tests for any Torchs factor. The individual prevalence rates were: 1.5% (10/685) for toxoplasmosis; 1.3% (8/618) for rubella; 1.3% (8/597) for cytomegalovirus; 0.9% (6/653) for hepatitis B and 3.7% (20/545) for hepatitis C; and 3.8% (25/664) for syphilis. The HIV Vertical HIV transmission was 4.6% among Gtp pregnant women and 1.2% among Gtn women. Antiretroviral therapy (ARV), vertical transmission, low birth weight and neonatal complications were significantly associated with Torchs positivity in univariate analysis. CONCLUSIONS: The Torchs prevalence found in the study was high for some infections. These findings emphasize the need to promote serological Torchs screening for all pregnant women, especially HIV-infected women, so that an early diagnosis can be made and treatment interventions can be implemented to prevent vertical HIV transmission.

Prevalência de infecções congênitas e perinatais em gestantes HIV positivas da região metropolitana de Belo Horizonte / Prevalence of congenital and perinatal infection in HIV positive pregnant in Belo Horizonte metropolitan region

OBJETIVOS: Avaliar a prevalência de toxoplasmose, rubéola, citomegalovirose, hepatites B e C e sífilis (Torchs) em uma coorte de gestantes, bem como identificar os fatores sociodemográficos, clínicos e laboratoriais.MÉTODOS: Entre 1998 e 2013, foram atendidas 1.573 gestantes com sorologia positiva para o HIV em área metropolitana do Brasil, das quais 704 (44,8%) foram submetidas a algum dos testes sorológicos. Gestantes Torchs positivas (Gtp) foram consideradas aquelas com resultado positivo para uma dessas infecções, e gestantes Torchs negativas (Gtn) aquelas com resultados negativos para todas elas. As variáveis maternas investigadas foram: idade, estado civil, escolaridade, momento e forma de contágio da infeccção pelo HIV, contagem de linfócitos TCD4+, carga viral plasmática do HIV próxima ao parto e uso de terapia antirretroviral durante a gestação. As variáveis neonatais investigadas foram ocorrência de: transmissão vertical, prematuridade, baixo peso ao nascimento, complicações fetais, aborto e óbito fetal. Foram utilizadas razões de chance com intervalo de confiança de 95% para quantificar a associação entre as variáveis maternas e neonatais e a presença de Torchs.RESULTADOS: Entre as 704 gestantes, 70 (9,9%; IC95% 7,8-12,4) tinham alguma sorologia positiva para Torchs. Foram encontradas taxas: 1,5% (10/685) para a toxoplasmose; 1,3% (8/618) para rubéola; 1,3% (8/597) para citomegalovirose; 0,9% (6/653) para hepatite B e 3,7% (20/545) para hepatite C; e 3,8% (25/664) para sífilis. A transmissão vertical do HIV entre as gestantes Gtp foi 4,6% e de 1,2% entre as Gtn. As variáveis associadas à presença de Torchs na análise univariada foram: uso de terapia antirretroviral, transmissão vertical do HIV, baixo peso ao nascimento e complicações fetais.CONCLUSÃO: A prevalência das Torchs mostrou-se elevada para algumas infecções. Conclui-se que é importante manter o rastreamento de Torchs na gravidez, especialmente nas gestantes HIV positivas, para que se possa estabelecer diagnóstico e tratamento, e/ou medidas preventivas para evitar a transmissão materno-fetal.

PURPOSE: To evaluate the prevalence of toxoplasmosis, rubella, cytomegalovirus, hepatitis B&C and syphilis (Torchs) in a cohort pregnant women and to identify the sociodemographic, clinical and laboratory factors.METHODS: A total of 1,573 HIV-infected pregnant women from a Brazilian metropolitan region were studied between 1998 and 2013. The results of serological tests were available for 704 (44.8%) pregnant women. Pregnant women were considered to be Torchs positive (Gtp) when they had positive results for at least one of these infections, and to be Torchs negative (Gtn) when they had negative results for all of them. Maternal covariables were: age, marital status, educational level, time and mode of infection, CD4 lymphocyte count, viral load at delivery, and use of antiretroviral therapy (ARV). Neonatal covariables were: HIV infection, prematurity, low birth weight, neonatal complications, abortion and neonatal death. Odds ratios with 95% confidence interval were used to quantify the association between maternal and neonatal variables and the presence of Torchs.RESULTS: Among 704 pregnant women, 70 (9.9%; 95%CI 7.8-12.4) had positive serological tests for any Torchs factor. The individual prevalence rates were: 1.5% (10/685) for toxoplasmosis; 1.3% (8/618) for rubella; 1.3% (8/597) for cytomegalovirus; 0.9% (6/653) for hepatitis B and 3.7% (20/545) for hepatitis C; and 3.8% (25/664) for syphilis. The HIV Vertical HIV transmission was 4.6% among Gtp pregnant women and 1.2% among Gtn women. Antiretroviral therapy (ARV), vertical transmission, low birth weight and neonatal complications were significantly associated with Torchs positivity in univariate analysis.CONCLUSIONS: The Torchs prevalence found in the study was high for some infections. These findings emphasize the need to promote serological Torchs screening for all pregnant women, especially HIV-infected women, so that an early diagnosis can be made and treatment interventions can be implemented to prevent vertical HIV transmission.

Elevated circulating ghrelin, but not peptide YY(3-36) levels, in term neonates with infection.

BACKGROUND: Early diagnosis and treatment of neonatal infection is important to prevent morbidity and mortality. The gastrointestinal tract-derived hormones ghrelin and peptide YY (PYY), which participate in the regulation of food intake and energy balance, may also play roles in the inflammatory response. Their involvement in neonatal infection is not known. METHODS: Plasma ghrelin and PYY(3-36) levels were serially measured (by ELISA) on Days 0, 1, 2, 3 and 7 following admission in 36-term neonates with febrile infection (22 of them were septic) and once in 20 healthy term neonates of similar postnatal age and gender distribution, as controls. Associations of ghrelin and PYY(3-36) levels with clinical and laboratory parameters, including anthropometrics, fever, leukocyte and platelet counts, serum glucose, C-reactive protein (CRP) and serum amyloid A levels, were assessed. RESULTS: Plasma ghrelin levels were significantly higher in infected neonates than in controls at each study day (p=0.009), whereas PYY(3-36) levels did not differ significantly between patients and controls at any day. In infected neonates, ghrelin levels on admission correlated negatively with serum glucose levels (p=0.003), whereas fever change during the course of infection was significantly associated with change of ghrelin levels (p=0.01). Receiver operating characteristic analysis of ghrelin levels resulted in significant areas under the curve (AUC) for detecting infected neonates on admission (AUC=0.728, p=0.005). CONCLUSIONS: Circulating ghrelin, but not PYY(3-36), levels are increased in neonates with infection, possibly reflecting and/or participating in the inflammatory process.

[Congenital and perinatal infections in the Marche region (Italy): an epidemiological study and differences between ethnic groups]. / Le infezioni congenite e perinatali nella regione Marche (Italia). Studio epidemiologico e differenze tra gruppi etnici.

The purpose of this study was to evaluate the epidemiological data regarding congenital and perinatal infections in the Marche region to verify the existence of differences in relation to maternal country of origin. This prospective study was conducted from May 2001 to April 2012, and it involved all the maternity units of the Marche region. A total of 10232 pregnant women were included, 25.1% of whom were of foreign nationality while the number of births totalled 10371. Estimated uptake of antenatal screening was 80.5% for CMV infection, 98.6% for HBV infection, 97.5% for HCV infection, 97.4% for HIV infection, 93.1% for syphilis and 98.5% for toxoplasmosis. For group B streptococcus vaginal and perianal swabs were performed in 81.2% of all women (78.4% in immigrant and 90.4% in Italian women; the difference was statistically significant [p 0.001]) and 13.6% were positive. The overall prevalence for CMV infection was 72.3% (91.9% in immigrant women) while for toxoplasmosis it was 27.5% (28.8% in immigrant women). The rate of seroconversion in pregnant women investigated for CMV infection was 0.28%, while that for toxoplasmosis was 0.09%. The overall prevalence for HBV infection was 0.79% (4.3% in immigrant and 0.4% in Italian pregnant women; the difference was statistically significant [p 0.001]), 0.4% for HCV infection (1% in immigrant and 0.48% in Italian pregnant women; the difference was not statistically significant [p 0.413]), 0.22% for syphilis (0.8% in immigrant and 0.08% in Italian pregnant women; the difference was not statistically significant [p 0.062]), 0.09% for HIV infection, and 0.03% for tuberculosis. The prevalence of congenital CMV infection was 0.04% and that of congenital toxoplasmosis 0.01%. The prevalence of early-onset infection from Group B streptococcus was 0.029%. No cases were observed of congenital syphilis, congenital tuberculosis or maternal and neonatal HSV infections. The study proves that in the Marche region there is a high percentage of women who undergo prenatal screening, including screening for infections, not offered by the National Health Service, such as CMV and HCV. The data also demonstrate that some infections, such as tuberculosis, HIV and HBV, almost exclusively affect immigrant women. Regarding neonatal infections, the data presented are in line with those in the literature, with the exception of congenital CMV infection, in which the low prevalence observed could be linked to the recent and massive migration of already immunized women.

Hypoxic/ischemic and infectious events have cumulative effects on the risk of cerebral palsy in very-low-birth-weight preterm infants.

BACKGROUND: Hypoxia/ischemia and inflammation are two major mechanisms for cerebral palsy (CP) in preterm infants. OBJECTIVE: To investigate whether hypoxia/ischemia- and infection-related events in the perinatal and neonatal periods had cumulative effects on CP risk in very-low-birth-weight (VLBW) premature infants. METHODS: From 1995 to 2005, 5,807 VLBW preterm infants admitted to Taiwan hospitals were enrolled. The cumulative effects of hypoxic/ischemic and infectious events during the perinatal and neonatal periods on CP risk at corrected age 24 months were analyzed. RESULTS: Of the 4,355 infants with 24-month follow-up, 457 (10.5%) had CP. The CP group had significantly higher incidences of hypoxia/ischemia-related events in the perinatal and neonatal periods, and sepsis in the neonatal period than the normal group. Three hypoxic/ischemic events, including birth cardiopulmonary resuscitation (OR 2.25; 95% CI 1.81-2.82), patent ductus arteriosus (PDA) ligation (2.94; 1.35-5.75) and chronic lung disease (3.14; 2.61-3.85) had the most significant contribution to CP. Relative to CP risk for infants with neither the three hypoxic/ischemic events nor sepsis, the CP odds increased 1.98-, 2.26- and 2.15-fold for infants with birth cardiopulmonary resuscitation, PDA ligation and chronic lung disease, respectively; while the combination with sepsis further increased the odds to 3.18-, 3.83- and 3.25-fold, respectively. Using the three hypoxic/ischemic events plus sepsis, CP rates were 10.0, 16.7, 26.7, 40.0 and 54.7% for infants with none, one, two, three and four events, respectively. CONCLUSIONS: Hypoxic/ischemic and infectious events across the perinatal and neonatal periods exerted cumulative effects on CP risk in VLBW premature infants.

Inhibitors of gastric acid secretion drugs increase neonatal morbidity and mortality.

AIMS: To analyze all evidence on the possible increase in morbidity and mortality determined by the use of inhibitors of gastric acid secretion (IGAS) drugs. MATERIALS AND METHODS: We review all evidence exploring the adverse events associated with IGAS use in neonates. RESULTS: Despite being prescribed in an off-label manner because of the perceived safety and potential benefit demonstrated for older populations, IGAS are being increasingly used in the neonatal period with much evidence derived from adults and children. Few data are available for neonates and indicate an association between IGAS use with infections and necrotizing enterocolitis (NEC), and with an increased mortality. Delayed gastric emptying, increased gastric mucus viscosity, modification in microbiota, and impairment of neutrophils functions are possible mechanisms of adverse events associated with IGAS use. CONCLUSIONS: A careful prescription of IGAS is crucial in order to reduce iatrogenic damage in neonates.

Neonatal infection-associated mortality in China, a population-based study, 2003-2008.

OBJECTIVE: To examine trends in the major causes and rates of neonatal infection-associated mortality (NIMRs) in different geographical regions in China from 2003 to 2008. METHODS: Neonatal mortality data collected from the Chinese National Women and Children's Health Surveillance Network were analyzed. RESULTS: The NIMRs declined. Pneumonia, sepsis and diarrhea were the top three infections that caused neonatal deaths. Compared to the coastal region, the relative risk (RR) of NIMRs in the remote and inland regions declined from 5.52 (95% CI: 4.05-7.52) and 2.37 (95% CI: 1.72-3.25) during 2003-2005 to 3.45 (95% CI: 2.58-4.61) and 1.72 (95% CI: 1.28-2.31) during 2006-2008, respectively. Once again, compared to the coastal region, the risk of pneumonia-specific mortality had significant regional disparities during 2006-2008 with a RR of 3.82 (95% CI: 2.74-5.32) in the remote region and 2.01 (95% CI: 1.44-2.80) in the inland region. The NIMRs in the remote region was characterized by more home deliveries and non-healthcare seeking behavior prior to death than the coastal region. CONCLUSIONS: Infection is still one of the main causes of neonatal mortality in China. Although the NIMRs have been declining, disparities concerning neonatal infection-associated and pneumonia-specific neonatal morality still exist. Approaches for reducing mortality of neonatal infections will efficiently decrease total neonatal mortality.