Symptomatic Babies Research Articles

Is a Higher Amniotic Fluid Viral Load Associated with a Greater Risk of Fetal Injury in Congenital Cytomegalovirus Infection-A Systematic Review and Meta-Analysis.

Background: Numerous studies have aimed to predict prenatal and neonatal outcomes for pregnancies complicated by congenital cytomegalovirus (CMV). Presently, assessing CMV severity prenatally relies largely on fetal imaging. A controversy exists regarding CMV viral load (VL) and its association with fetal and neonatal sequelae. Objective: To perform a systematic review and meta-analysis investigating the association between CMV DNA VL in amniotic fluid and fetal and neonatal outcomes in pregnancies with congenital CMV. Results: All cohort, case-control and observational studies that compared outcomes of fetuses with congenital CMV and provided information on individual patient CMV VL quantified in copies per milliliter (c/mL) from inception to January 2023 were included, with no geographical or language restrictions. A total of 1251 citations were reviewed with eight studies meeting inclusion criteria and included in meta-analysis. Affected pregnancies had a higher VL in the amniotic fluid compared to those unaffected with a mean difference of 2.2e+7 (range 1.5e+7 to 2.8e+7). In subgroup analysis, the VL was significantly higher in the fetuses, with imaging findings related to CMV compared to asymptomatic fetuses with a mean difference of 4.1e+7 (95% CI 2.8e+7-5.4e+7). However, among babies with congenital CMV, the VL was not significantly different between symptomatic and asymptomatic babies. Conclusions: Amniotic fluid CMV VL is associated with fetal sequalae in congenital CMV, with a higher VL conferring a greater risk for prenatal injury.

New-born with Hypoglycaemia and their Neurodevelopmental Outcome: A Prospective Study in a Tertiary Care Hospital in Bangladesh

Background: Brain mainly utilizes glucose to maintain its basic function as well as higher order executive functions. Among metabolic problem, hypoglycaemia in the most common in new-born nursery as well as Neonatal Intensive Care Unit (NICU). Hypoglycaemia may adversely affect developing brain and cause neurological impairment. Objectives: The aim of this study was to assess the neurodevelopmental outcome of new-borns with hypoglycaemia admitted in NICU. Methods: This prospective observational study was conducted in the department of Neonatology and Institute of Paediatric Neuro-disorder and Autism (IPNA), Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka from March 2020 to August 2021. The inclusion criteria were babies admitted in NICU with hypoglycaemia or developed hypoglycaemia. Consent was taken from the parents/guardians whose baby develop hypoglycaemia (blood glucose <2.6 mmol/L). Hypoglycaemia was detected by capillary blood glucose estimation by heel prick tests and confirmed by corresponding blood sugar (RBS). Hypoglycaemia was treated by ensuring feeding or glucose infusion as per standard departmental treatment protocol. New-borns were followed up at 6 and 12 months of age and their neurodevelopmental assessment was done by Bayley Scales of Infant and toddler Development III (BSID III). Data were analysed using the SPSS 22.0 version software. Result: Among 66 admitted hypoglycaemic neonates 62 babies neurodevelopmental assessment was done at 6 and 12 months by BSID III method. Among them 48.5% were males while 51.5 % were females, 24.24% were gestational age <34 weeks, 36.36% were between gestational age 34 – < 37 weeks and 39.39% were ≥37 weeks of gestation. 60 (90.9%) babies were inborn whereas 6 (9.1%) were out born. Among hypoglycaemic neonates, normal birth weight (≥2500 g) were 27.27%, low birth weight (1500 – <2500 g) were 39.39% and rest of the babies (33.33%) were < 1500 g. IDM was 42.4% and IUGR was 33.3%. Most patient developed hypoglycaemia within 24 hrs of age (48.55%), among them 13.6% were symptomatic and 46% required glucose infusion. At 1st follow up overall adverse outcome (composite score < 70 in BSID III) were 19.4% and at 2nd follow up overall adverse outcome were 12.9%. Hypoglycaemia with very low birth weight, hypothermia and symptomatic babies were significantly associated with adverse neurodevelopmental outcome. Conclusion: Among hypoglycaemic new-borns those were symptomatic, very low birth weight and hypothermic were more prone to develop adverse neurodevelopmental outcome.

Asymmetrical Septal Hypertrophy: A Rare Case of Respiratory Distress in an Infant of a Diabetic Mother

Cardiomyopathy is a disease that affects the myocardium and causes mechanical or electric dysfunction. Hypertrophic cardiomyopathy comprises various cardiac components such as thickening of ventricular walls, hypertrophy of interventricular septum thereby resulting in subaortic stenosis, systolic and/or diastolic dysfunction. This cardiac complication is a known but rare entity in infants of diabetic mothers wherein the clinical presentation ranges from being asymptomatic to respiratory distress to congestive cardiac failure. Incidence of Congenital Heart Disease in infants of Diabetic Mothers is 5% and the percentage of symptomatic HOCM babies is 12%. Here, we report a term neonate, born to a G2P2L2 mother with Gestational Diabetes Mellitus with poor glycemic control, presenting with respiratory distress manifesting as silent tachypnea at 24 hours of life, diagnosed as Asymmetrical Septal Hypertrophy on 2D-Echo, treated successfully with Propranolol and showed resolution of hypertrophy in follow-up echocardiography. In this condition, foetal hyperinsulinemia is responsible for an increase in synthesis and deposition of fat and glycogen in the myocardial cells which explains the cardiac hypertrophy. Due to increase in the thickness of the Interventricular Septum, there is Left Ventricular Hypertrophy and during systole, the systolic anterior motion of the anterior leaflet (SAM) of the aortic valve is elongated. Therefore, due to this obstruction of the orifice by the aortic valve, there is reversal of blood flow clinically manifesting as Silent Tachypnea. Symptomatic babies are treated with Oral Propranolol which acts by improving left ventricular outflow obstruction.

Antibiotikumhasználat korai szepszis gyanúja esetén újszülöttkorban

Early-onset neonatal sepsis is a rare, but life-threatening condition. In 2017, the Hungarian Neonatal Society issued a national guideline to rationalize the use of antibiotic use in neonatal sepsis. To retrospectively determine the frequency of prescribed antibiotics before and after the introduction of national guidance. Data of neonates (>34. gestational weeks) delivered in our hospital between 1st January 2014 and 31st December 2018 were analysed with focusing on signs of sepsis, number of neonates treated with antibiotics, incidence of early-onset neonatal sepsis, sepsis-related mortality. Statistical analysis was performed with RStudio software (significance: p<0.05). During the analysed time period, 12 347 neonates were born, 1502 (12.16%) neonates were given antibiotics, showing a significant decrease after 2017: 517 (21.10%) in 2014, 401 (16.63%) in 2015, 459 (17.96%) in 2016, 61 (2.39%) in 2017, 64 (2.69%) in 2018, respectively. Out of the group of neonates treated with antibiotics (n = 1502), only 239 (15.91%) neonates showed the clinical signs of sepsis. No significant change was observed in the number of symptomatic newborns during the study period: 52 (2.12%) in 2014, 42 (1.74%) in 2015, 42 (1.64%) in 2016, 46 (1.80%) in 2017, 57 (2.40%) in 2018, p = 0.285. Blood culture confirmed neonatal sepsis was observed in 4 babies, incidence of early-onset neonatal sepsis was 0.324/1000, sepsis-related mortality was zero. Before the introduction of the national guideline, most of the neonates were prescribed antibiotics based on risk factors. Since 2017, antibiotics have been mainly preserved for newborns with clinical signs of sepsis. Despite cessation of antiobiotic treatment indicated by risk factors, the number of symptomatic babies and sepsis-related mortality have not increased. The use of antibiotics for neonates >34th gestational week can be safely reduced, entailing a decrease in short- and long-term complications of early antibiotic use. Orv Hetil. 2022; 163(11): 431-437.

Neonatal outcome in COVID-19 pregnant women in District Hospital, Ballari

Objectives: This study aims to study the neonatal COVID-19 incidence and outcome in District Hospital, Ballari. Materials and Methods: This is a retrospective analytic study of 171 neonates born to COVID-19-positive pregnant women delivered at District Hospital, Ballari, Karnataka, during the period of April 2020–September 2020. Results: The study was conducted among 171 babies delivered to COVID-19-positive pregnant women delivered in District Hospital, Ballari. Out of which, 62 babies were admitted in SNCU for various indications such as respiratory distress syndrome (4), meconium aspiration syndrome (8), other causes of respiratory distress (13), birth asphyxia (8), neonatal jaundice (14), hypoglycemia (1), preterm care (8), and neonatal COVID-19 (1). Out of 171 neonates born to COVID-19-positive mothers, only 7 (4%) neonates were tested positive for reverse transcription-polymerase chain reaction. A total of three babies were symptomatic, among those, two had refusal of feeds and one had respiratory distress and hypernatremic dehydration. Conclusion: In this study, COVID-19-positive neonates had milder manifestation with transmission rate of 4%. All symptomatic babies got cured and discharged successfully with average length of stay for 4 days. Although our conclusions are limited, the findings conclude that neonatal COVID-19 outcome is not as severe as seen in adults.

The outcome of fetuses diagnosed with congenital cystic adenomatous malformation of the lungs: Experience of a regional neonatal center (2004–2016)

Objective: Although much is known about the antenatal course of congenital cystic adenomatous malformation (CCAM), the postnatal course is less well documented. The vast majority of infants remain asymptomatic at birth, with the controversy surrounding the postnatal management of such infants. We reviewed the outcome of fetuses diagnosed with CCAM in our center and evaluated their symptom burden during the 1st year of life. Methods: A retrospective review of maternal and infant medical records of all cases with antenatal diagnosis of CCAM managed in a regional perinatal center over 12 years, and infant outcome at 1 year of age is presented. Results: Forty-two eligible singleton pregnancies/infants were identified. Thirteen babies (30.9%) were symptomatic and 29/42 (69.1%) asymptomatic at birth. 7/13 (53.9%) symptomatic infants had associated antenatal complications. The fetal lesions were more likely to remain static or reduce in size during pregnancy in asymptomatic (26/29; 89.6%) than symptomatic babies (8/13; 61.6%). All babies had chest radiographs after birth, but computed tomography (CT) scan was done in only a few symptomatic babies; 7/42 (16.7%) during the neonatal period and a further 3/42 (7.1%) during infancy. The majority (8/13; 61%) of the symptomatic babies had surgical intervention compared to only 1/29 (3.4%) asymptomatic babies who had surgery. However, most babies remained symptom-free during infancy. Death within the cohort was limited to babies who were symptomatic (4/13; 31%). Conclusion: Most pregnancies diagnosed with CCAM remain uncomplicated. The behavior of the prenatal lesion could help predict the postnatal outcome. Our experience highlights that CCAM persistence cannot be excluded from chest radiographs; hence, the need for chest CT scans. Symptom surveillance should help guide the need for surgery in asymptomatic infants. However, only skilled clinicians who can offer long-term follow-up, until the transition into adulthood should oversee surveillance to ensure safety.

Early stoppage of antibiotics in blood culture negative term suspected early onset sepsis and their 7 days outcome

Introduction: Sepsis is the commonest cause of neonatal mortality; it is responsible for about 30-50% of the total neonatal deaths in developing countries. It is estimated that up to 20% of neonates develop sepsis and approximately 1% die of sepsis related causes. Despite receiving extensive care in hospitals in the form of ventilator and inotropic support in intensive care set up, 2-3% of term and 20-30% of preterm infants still die of early onset sepsis (EOS). Clinical suspicion therefore frequently leads to empirical antibiotic therapy in uninfected infants. Treating an uninfected infant for 5 to 7 days means disrupting maternal bonding and breast feeding for an extended period of time, pain and distress from starting IVs, exposing the infant to drugs with potential toxicities, fostering the development of antibiotic resistant flora, and increasing the probability that the infant will experience a more serious morbidity later in the course of hospitalization. Material and Method: The study cohort consisted of the all term babies hospitalised with early onset sepsis to the S.C.B M.C.H and S.V.P.P.G.I.P, Cuttack from October 2016 to September 2018. Result: Out of total 186 neonates with suspected early onset sepsis, majority were male (64%) and 93% presented within 24 hours of life. The most common perinatal risk factor noted was low birth weight (43%) followed by perinatal asphyxia (24.2%). 96.2% of the neonates were symptomatic at the time of admission; the most common symptom being respiratory distress (73.6%). The blood culture was positive in 25.8% babies. The incidence of culture positive sepsis in symptomatic babies was 27%. None of the asymptomatic babies were culture positive. Only 49% of screen positive babies were blood culture positive. Antibiotics were stopped in 133 babies and unnecessary use of antibiotics was reduced by 82.6%. No sepsis related adverse outcome was noted in 7 days following stoppage of antibiotics. Conclusion: It is safe to stop antibiotics in term EOS babies if the 48 hour blood culture is negative and baby is asymptomatic.

Management of hypoglycemia in newborn: Turkish Neonatal and Pediatric Endocrinology and Diabetes Societies consensus report.

Hypoglycemia is one of the most important and most common metabolic problems of the newborn because it poses a risk of neurological injury, if it is prolonged and recurs. Therefore, newborns who carry a risk of hypoglycemia should be fed immediately after delivery and the blood glucose level should be measured with intervals of 2-3 hours from the 30th minute after feeding. The threshold value for hypoglycemia is 40 mg/dL for the first 24 hours in symptomatic babies. In asymptomatic babies, this value is considered 25 mg/dL for 0-4 hours, 35 mg/dl for 4-24 hours, 50 mg/dL after 24 hours and 60 mg/dL after 48 hours. Screening should be performed with bed-side test sticks. When values near the limit value are obtained, confirmation with laboratory method should be done and treatment should be initiated, if necessary. The level targeted with treatment is considered 50 mg/dL in the postnatal first 48 hours before feeding, 60 mg/dL after 48 hours in babies with high risk and above 70 mg/dL in babies with permanent hypoglycemia. In cases in which the blood glucose level is below the threshold value and can not be increased by feeding, a glucose infusion of 6-8 mg/kg/min should be initiated. If symptoms accompany, a mini bolus of 10% dextrose (2 ml/kg/min) should accompany. Incements (2 mg/kg/min) should be performed, if the target level can not be achieved and decrements (2 ml/kg/ min) should be performed, if nutrition and stabilization is provided. The infusion should be discontinued, if the infusion rate decreases to 3-5 mg/ kg/min. If necessary, blood samples should be obtained during hypoglycemia in terms of differential diagnosis and the investigation should be performed following a 6-hour fasting period in babies fed enterally and at any time when the plasma glucose is <50 mg/dL in babies receiving parenteral infusion. The hypoglycemic babies in the risk group whose infusions have been terminated can be discharged, if the plasma glucose level is found to be at the target level for two times before feeding and babies with permanent, severe or resistant hypoglycemia can be discharged, if the plasma glucose level is >60 mg/dL following a 6-hour fast.

Use Judiciously, or I Will Be Useless” A Clinical Audit on Use of Antibiotics Within First 72 hrs of Life in Symptomatic Term Babies With no Maternal Risk for Infection

Use Judiciously, or I Will Be Useless” A Clinical Audit on Use of Antibiotics Within First 72 hrs of Life in Symptomatic Term Babies With no Maternal Risk for Infection

Neonatal and long-term ophthalmological findings in infants with symptomatic and asymptomatic congenital cytomegalovirus infection

BackgroundCongenital cytomegalovirus (cCMV) infection is responsible of a high burden of neurosensory impairment in children. ObjectivesTo report incidence and consequences of ophthalmological abnormalities in infants with cCMV infection and better define their long-term ophthalmological management. Study designInfants with cCMV infection were enrolled in a 6-year follow-up. Infants were classified as symptomatic or asymptomatic based on complete clinical, laboratory and instrumental evaluations. All infants underwent funduscopic evaluation in neonatal period, and yearly complete ophthalmological evaluation, including funduscopic, motility and visual acuity assessments. ResultsForty-eight infants were enrolled, 18/48 (37.5%) symptomatic and 30/48 (62.5%) asymptomatic. Mean duration of follow-up was 34.9±22.2 vs. 34.8±20.1months (P=0.98). Funduscopic abnormalities were identified in neonatal period in 7/18 (39%) symptomatic infants and in none of the infants without other clinical and instrumental abnormalities at birth (P<0.001); chorioretinal scars were the most common finding (5/18 cases, 28%). Strabismus was detected in 1/18 (5.5%) symptomatic infants during the first years of life. Visual impairment at last follow-up evaluation was suspected or detected in 4/18 (22%) symptomatic infants and in none of the asymptomatic infants at birth (P=0.01). Ophthalmological abnormalities were associated with other signs of central nervous system (CNS) involvement (P<0.001). No correlation was found with the type of maternal infection. ConclusionsOphthalmological abnormalities were common in symptomatic infants though often not associated with long-term visual impairment, and correlated with the presence of CNS involvement. Neonatal and periodical ophthalmological evaluations throughout childhood seem prudential for symptomatic babies. No ophthalmological abnormalities were detected in asymptomatic infants, who might therefore undergo more deferred evaluations.

Clinical suspicion of congenital heart diseases during well-baby follow-up and echocardiographic correlation

Background: Congenital heart disease (CHD), the most common cardiac malformation in the fetal and neonatal period, represents a heterogeneous group of defects with little known cause. Despite advances in detection and treatment, CHD accounts for 3% of all infant deaths and 46% of death from congenital malformations. CHD patients with minimum or no symptoms are frequently under diagnosed in areas with inadequate health services. The aim of this study was to investigate the role of clinical suspicion of congenital heart disease in babies who presented for well-baby follow-up against echocardiographic findings and to study the clinical spectrum of all the CHD that were diagnosed. Methods: The study involved analysis of data collected by the authors while working in a tertiary care center at Mumbai, India, during 2009 to 2010. All the babies born from April 2009 to August 2010 (17 months) and those who came for well-baby visits (with or without symptoms) were examined carefully for findings on cardiac examination including abnormalities of heart sound and presence of murmur on auscultation. Findings of the echocardiography were recorded for follow up and all the babies were followed up on at least three-monthly basis. Echocardiography was repeated on a quarterly basis in symptomatic babies and six-monthly basis in asymptomatic babies with small septal defects. All the babies on follow up were closely monitored clinically and on echocardiography for ascertaining the natural course of the observed defects. Results: A total of 1856 babies were born at the tertiary care center out of which 1688 were seen at the well-baby clinic. A total of 42 cases were referred for echocardiography on clinical suspicion of CHD and out of these 21 (50%) were positive for some form of CHD. Most common CHD diagnosed was atrial septal defect (ASD). There was no spontaneous closure of ventricular septal defects (VSD), though, 02 cases of ASD less than 3 mm closed during the during the follow up period.Conclusions: This study demonstrated that clinical experience is a valuable tool in early diagnosis of CHD, even if they are asymptomatic. Early echocardiography is justified to diagnose the cases so that appropriate follow-up and management decisions could be planned. Though majority of the cases were moderate to small ASD and VSD, there is a need to diagnose them early and follow them up till closure.

Study of incidence, clinical profile and risk factors of neonatal hypoglycemia in a tertiary care hospital

Background: The reported incidence of hypoglycemia varies with its definition. The clinical manifestations of hypoglycemia are nonspecific and similar to those of many disorders in newborn infants. Persistent hypoglycemia is more likely to be associated with possible neurologic sequelae. However, its definition, clinical significance, and management remain controversial. Methods: This prospective observational study was done over a period of 2 years. Babies admitted to Neonatal intensive care unit with whole blood sugar levels <40 mg/dl and fulfilling inclusion criteria were taken up for the study. These babies were subjected to detailed history taking, thorough clinical examination and investigations. The babies were observed for signs and symptoms of hypoglycemia. Results: Neonatal hypoglycemia constituted about 8.26%. Majority of hypoglycemic babies were preterm babies. Asymptomatic hypoglycemia was predominantly noticed in preterm babies (65.21%). Term babies (58.82%) showed more symptoms with hypoglycemia than preterm babies. The major clinical manifestations are jitteriness, lethargy, convulsions and apneic spells. PIH and prematurity are most associated risk factors. Significantly low Sugar levels (p value <0.005) were noticed in symptomatic hypoglycemic babies. Conclusion: Hypoglycemia in neonates can have variable presentations indicating the need for detailed and thorough examination for evidence of hypoglycemia. Identification of risk factors of hypoglycemia and proper monitoring blood glucose levels should be done to plan early treatment and prevent neurological damage.

Clinical and laboratory features of congenital malaria in Nigeria

Since congenital malaria had previously been thought to be rare, blood film examination for malaria parasites is still sometimes not routinely performed in ill neonates in malaria-endemic regions. Because of increasing published reports of congenital malaria in Nigeria, there is a need to characterize the clinical and laboratory manifestations associated with malaria parasitemia within the first few hours of life. In a 12-month (April 2003-March 2004), multicenter study in Nigeria, thin and thick blood smears made from maternal (finger prick), placental aspirates, cord blood and neonate (heel prick taken within 4 hours of life) were Giemsa-stained and examined by light microscopy for asexual stages of Plasmodium. Parasitemic neonates were closely monitored for clinical and laboratory features of symptomatic malaria. Plasmodium falciparum was found in 5.1% (95/1875) of neonatal heel pricks; mean parasite density was low (mean = 48/μL, range 8–200/μL). Antepartum maternal and placental parasitemia were the most important risk factors for congenital parasitemia ( P P P 37.5°;) within the first 24 hours of life (100%) and refusal to suck (10.8%). Anemia at birth (hematocrit P = 0.03, OR = 1.84). The mean hematocrit of parasitemic neonates within 4 hours of life was 49.5 ± 6.4 as compared to 52.6 ± 8.2 in non-parasitemic babies ( P = 0.001). Furthermore, the mean hematocrit was 44.0 ± 5.5% in the symptomatic parasitemic babies. All symptomatic babies were treated with oral chloroquine with a cure rate of 89.1%. Treatment failures subsequently received oral sulfadoxine-pyrimethamine with good outcome. The febrile newborn should be evaluated for malaria especially if there is a history of prolonged labor or in the presence of maternal malaria infection. Efforts should be intensified to reduce the burden of maternal, placental malaria and therefore congenital malaria.

Monotherapy with Amikacin or Piperacillin-Tazobactum Empirically in Neonates at Risk for Early-Onset Sepsis: A Randomized Controlled Trial

Neonates at risk for early-onset sepsis are started on antibiotics empirically. Antibiotic resistance to conventionally used antibiotics is increasingly being reported. Antenatal maternal antibiotic exposure in this setting contributes to low yield on blood culture drawn at birth, limiting the planning of antibiotics based on culture reports. A head-to-head comparison for selecting the appropriate antibiotic is one strategy. To compare monotherapy with amikacin against piperacillin-tazobactum as an empirical therapy in neonates at risk for early-onset sepsis. Randomized open-label controlled trial with stratification and block randomization. Tertiary care neonatal unit in India All consecutive inborn neonates delivered between 01 May 2009 and 30 April 2011 who were ≥28 week gestation and/or ≥1000 g birth weight with risk factors for early-onset sepsis. Randomized to receive either amikacin or piperacillin-tazobactum, after stratifying as asymptomatic or symptomatic within 1 h of birth. Incidence of treatment failure to the allocated antibiotic defined as blood culture isolate reported resistant to the allocated antibiotic or progression of the illness, necessitating a change of antibiotic. Of 204 eligible cases, 187 were enrolled. Seventeen babies were excluded. A total of 128 neonates were stratified as asymptomatic and 59 as symptomatic. In all, 64 of the asymptomatic cases received amikacin and 64 received piperacillin-tazobactum, while 29 symptomatic babies received amikacin and 30 received piperacillin-tazobactum. Five babies had blood culture-positive sepsis, and 28 babies had strong suspicion of sepsis. There was no difference in the treatment failure in the amikacin group (3 of 93; 3.2%) compared with piperacillin-tazobactum group (2 of 94; 2.1%) (p > 0.01) and no difference in the incidence of second infection, fungal sepsis and all-cause mortality at day 7 and 28 between the two study groups (p > 0.01). Monotherapy with amikacin as an empirical antibiotic did not result in a higher incidence of treatment failure in neonates at risk for early-onset sepsis as compared with piperacillin-tazobactum. Both antibiotics were effective in management of babies with early-onset sepsis.

HCMV infection of human trophoblast progenitor cells of the placenta is neutralized by a human monoclonal antibody to glycoprotein B and not by antibodies to the pentamer complex.

Human cytomegalovirus (HCMV) is the major viral cause of congenital infection and birth defects. Primary maternal infection often results in virus transmission, and symptomatic babies can have permanent neurological deficiencies and deafness. Congenital infection can also lead to intrauterine growth restriction, a defect in placental transport. HCMV replicates in primary cytotrophoblasts (CTBs), the specialized cells of the placenta, and inhibits differentiation/invasion. Human trophoblast progenitor cells (TBPCs) give rise to the mature cell types of the chorionic villi, CTBs and multi-nucleated syncytiotrophoblasts (STBs). Here we report that TBPCs are fully permissive for pathogenic and attenuated HCMV strains. Studies with a mutant virus lacking a functional pentamer complex (gH/gL/pUL128-131A) showed that virion entry into TBPCs is independent of the pentamer. In addition, infection is blocked by a potent human neutralizing monoclonal antibody (mAb), TRL345, reactive with glycoprotein B (gB), but not mAbs to the pentamer proteins pUL130/pUL131A. Functional studies revealed that neutralization of infection preserved the capacity of TBPCs to differentiate and assemble into trophospheres composed of CTBs and STBs in vitro. Our results indicate that mAbs to gB protect trophoblast progenitors of the placenta and could be included in antibody treatments developed to suppress congenital infection and prevent disease.

Intrauterine Growth Restriction Caused by Underlying Congenital Cytomegalovirus Infection

Human cytomegalovirus (HCMV) is the major viral etiology of congenital infection and birth defects. Fetal transmission is high (30%-40%) in primary maternal infection, and symptomatic babies have permanent neurological, hearing, and vision defects. Recurrent infection is infrequently transmitted (2%) and largely asymptomatic. Congenital infection is also associated with intrauterine growth restriction (IUGR). To investigate possible underlying HCMV infection in cases of idiopathic IUGR, we studied maternal and cord sera and placentas from 19 pregnancies. Anti-HCMV antibodies, hypoxia-related factors, and cmvIL-10 were measured in sera. Placental biopsy specimens were examined for viral DNA, expression of infected cell proteins, and pathology. Among 7 IUGR cases, we identified 2 primary and 3 recurrent HCMV infections. Virus replicated in glandular epithelium and lymphatic endothelium in the decidua, cytotrophoblasts, and smooth muscle cells in blood vessels of floating villi and the chorion. Large fibrinoids with avascular villi, edema, and inflammation were significantly increased. Detection of viral proteins in the amniotic epithelium indicated transmission in 2 cases of IUGR with primary infection and 3 asymptomatic recurrent infections. Congenital HCMV infection impairs placental development and functions and should be considered as an underlying cause of IUGR, regardless of virus transmission to the fetus.

Glycoprotein B genotyping in congenital/perinatal cytomegalovirus infection in symptomatic infants

Molecular epidemiological studies on circulating strains of CMV in cogenital/perinatal infections have not been done earlier in this region. To study the glycoprotein B genotypes in babies with symptomatic congenital/perinatal CMV infection and to assess the possible influence of genotype on the outcome of the infection. Clinical samples (blood and urine) of symptomatic babies are sent to the Virology Department of NCDC, Delhi for the diagnosis of congenital infections. 375 clinical samples of infants (newborn - 6 months old) were included for the study. Serum samples were subjected to ELISA for detection of IgM antibodies against CMV. DNA isolation and amplification of CMV genomic DNA targeting gB gene fragment by nested PCR, was carried out in the samples. The amplified fragment including the cleavage site was subjected to RFLP using restriction enzymes Rsal and Hinf1. They were also verified by sequencing using Big Dye Terminator chemistry. 75 samples out of 375 tested were confirmed positive for CMV infection by serology and PCR. Both RFLP and sequencing of gB gene fragment showed that gB 1, 2 and 3 genotypes were in circulation. gB 3 was the most prevalent genotype in symptomatic infants. Hepatosplenomegaly was the most common feature in gB-3 genotype of CMV. gB2 congenital CMV infection was more commonly associated with long term sequelae.

Nonpharmacological Management of Gastroesophageal Reflux in Preterm Infants

Gastroesophageal reflux (GOR) is very common among preterm infants, due to several physiological mechanisms. Although GOR should not be usually considered a pathological condition, its therapeutic management still represents a controversial issue among neonatologists; pharmacological overtreatment, often unuseful and potentially harmful, is increasingly widespread. Hence, a stepwise approach, firstly promoting conservative strategies such as body positioning, milk thickening, or changes of feeding modalities, should be considered the most advisable choice in preterm infants with GOR. This review focuses on the conservative management of GOR in the preterm population, aiming to provide a complete overview, based on currently available evidence, on potential benefits and adverse effects of nonpharmacological measures. Nonpharmacological management of GOR might represent a useful tool for neonatologists to reduce the use of antireflux medications, which should be limited to selected cases of symptomatic babies.

Dilemmas in the management of congenital cytomegalovirus (CMV)

<h3>Background</h3> Routine antenatal ultrasound screening revealed liver calcifications, and subsequent maternal serology (IgM and IgG) was shown to be positive for cytomegalovirus (CMV). Shortly after birth he was found to have hepatosplenomegaly, petechiae and visible jaundice. Bloods within the first few hours revealed marked conjugated jaundice, thrombocytopaenia and deranged coagulation. The baby was admitted to our neonatal unit for observation and treatment and congenital CMV infection was confirmed within 24 hours by positive CMV PCR from his urine. Further investigations revealed no intracranial abnormalities, no evidence of retinitis and normal newborn hearing. Abdominal ultrasound confirmed hepatic calcification and organomegaly. <h3>Management</h3> Following discussion between neonatal and paediatric infectious disease consultants, a decision was taken to treat the infant with IV ganciclovir for 2 weeks (necessitating insertion of a percutaneous long line), followed by oral valganciclovir for 4 weeks. Weekly Viral loads were checked, together with frequent monitoring for neutropaenia. <h3>Issues</h3> This case highlighted several dilemmas in the management of congenital CMV. CMV is the most frequent congenital infection and has a UK incidence of around 3-4/1000 live births. Around 10-15% of these infants will be symptomatic, of whom up to 90% will develop long term sequelae usually in the form of sensorineural hearing loss, visual impairment or developmental delay. Some 13% of asymptomatic infants also develop long term problems. In spite of such morbidity, decisions of whom to treat, and for how long, remain controversial. Whilst there is some support for treating infants with CNS symptoms, there is a paucity of high level evidence for treating infants with other organ involvement. In addition, the adverse effects of treatment - namely requirement of central venous access with its associated complications, and potential neutropaenia – are not inconsiderable. The controversies of treatment, and uncertainty regarding long term follow-up of symptomatic and asymptomatic babies, mean such cases provide difficult management problems.

Outbreak of a South West Pacific clone Panton–Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus infection in a UK neonatal intensive care unit

Panton-Valentine leucocidin-positive meticillin-resistant Staphylococcus aureus (PVL-MRSA) has become a globally common cause of community-acquired infections. We report an outbreak of PVL-MRSA in a regional neonatal unit in the UK involving three babies and three staff members. Quinolone susceptibility was helpful in identifying potential PVL-MRSA but toxin gene profiling and sequence-based typing were required to distinguish between two PVL-MRSA strains present in the unit. All three symptomatic babies and two staff carriers, one of whom was symptomatic, were found to be carrying the South West Pacific (SWP) clone of PVL-MRSA (ST30). One of the staff carriers had recently visited the Philippines and was thought to be the source of the outbreak. Control was established using standard infection control procedures but one baby with relapsing MRSA colonization has required more than 100 days in isolation. This is the first reported neonatal outbreak associated with the SWP clone in the UK. Our study highlights the potential risk of further introductions of this organism by healthcare staff or patients epidemiologically linked with the Philippines.