Yildiz Perk

Selective unresponsiveness to HBsAg vaccine in newborns related with an in utero passage of hepatitis B virus DNA

Thirty four out of 158 (22%) newborns to mothers chronically infected by the hepatitis B virus (HBV) did not produce antibodies (Ab) to HBsAg 1 month after the last injection of the HBV vaccine supplemented with HBV specific immunoglobulins. At birth, HBV genome was detected by polymerase chain reaction (PCR) in the peripheral blood mononuclear cells (PBMC) of a large majority (28 out of 34) of these non-responder newborns but never in the other newborns who responded to the HBsAg vaccine. HBV genome was detected in serum, only in some cases (nine out of 34) and never in the absence of HBV DNA in PBMC. For nine out of 14 followed newborns, the absence of response was transitory since anti-HBs Abs appeared after 15 months, without booster, while the HBV genome had disappeared. Unresponsiveness was specific to the HBV envelope protein since all late responders and 15-months-non-responders to the HBsAg vaccine produced normal levels of Abs to the three poliovirus serotypes, to tetanus toxoid and to the pneumococcus polysaccharides. An in utero induced immune tolerance to low doses of HBsAg appears as the most plausible hypothesis to explain this unresponsiveness to HBV vaccine.

A novel mutation in the interleukin-1 receptor antagonist associated with intrauterine disease onset

Deficiency of the IL-1 receptor antagonist (DIRA) is a recently described rare autoinflammatory disease, caused by loss of function mutations in IL1RN leading to the unopposed activation of the IL-1 pathway. We describe a novel nonsense mutation in the IL1RN gene, associated with early intrauterine onset, death and multiorgan involvement in a prematurely born baby. The protein prediction model indicated that the novel Q119X mutation would result in a nonfunctional protein by impairing the ability of the IL-1Ra to bind and antagonize signaling through the IL-1R. Since the disorder may mimic severe bacterial infections and the treatment with anakinra is life saving, we intend to raise awareness of the syndrome and the possibility of a founder mutation that may lead to the diagnosis of additional cases in Turkey. The clinical suspicion of DIRA is critical to avoid improper management of the patients with antibiotics alone and death from multiorgan failure.

Intraventricular hemorrhage in preterm newborns: Risk factors and results from a University Hospital in Istanbul, 8 years after

Background: In this prospective study, the authors aimed to show intraventricular hemorrhage (IVH) incidence of premature newborns in the Neonatal Intensive Care Unit of Cerrahpasa Faculty of Medicine, Istanbul, Turkey, and its risk factors, and they tried to compare these results with those they reported 8 years ago.

Seroprevalance of pertussis antibodies in maternal and cord blood of preterm and term infants

BACKGROUND The resurgence of pertussis has resulted in an increased morbidity and mortality, especially among young infants. The aim of our study was to determine the antibody concentrations against pertussis antigens in cord and maternal blood in both preterm and term infant-mother pairs and to evaluate the efficacy of transplacental antibody transfer. METHODS Antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in maternal and cord blood samples were measured by in-house enzyme linked immunosorbent assay (ELISA) in 100 preterm infant-mother and 100 term infant-mother pairs. Geometric mean concentrations (GMCs) of pertussis antibodies and cord:maternal GMC ratios were calculated. RESULTS Cord GMCs for anti-PT and anti-FHA in the preterm group were 13.15 and 14.55 ELISA U/ml (EU/ml), respectively. Cord GMCs for anti-PT and anti-FHA in the term group were 19.46 and 19.18 EU/ml, respectively. Cord anti-PT GMC was significanlty lower in the preterm group (p=0.037). There were no differences between the groups with regard to maternal anti-PT and anti-FHA GMC. Placental transfer ratios for anti-PT and anti-FHA in preterms were 68% and 72%, respectively. The same ratios in terms were 107% and 120%, respectively and were significantly higher than those of preterms (p<0.001). Placental transfer ratios were even lower in preterms <32 weeks when compared to preterms ≥32 weeks and terms. There was a strong correlation between maternal and cord anti-pertussis antibody levels both in preterm and term infants. CONCLUSIONS Anti-pertussis antibody levels were generally low in infant-mother pairs and would not be adequate to confer protection until the onset of primary immunization series. Transplacental anti-pertussis antibody transfers and antibody levels were lower in the cord blood of preterm infants, especially in those <32 weeks. These findings support the rationale for maternal immunization, which in combination with cocooning, could be a better option for preterm infants.

Prevalence of Prader-Willi Syndrome among Infants with Hypotonia

OBJECTIVE To investigate the prevalence of Prader-Willi syndrome (PWS) in infants with hypotonia between the ages of 0 and 2 years. STUDY DESIGN Karyotyping studies were performed in all infants with hypotonia. The study group was composed of infants with hypotonia for whom the karyotyping was found to be normal. Fluorescence in situ hybridization and methylation analysis were performed simultaneously in the study group. Molecular studies for uniparental disomy were undertaken in the patients without deletions with an abnormal methylation pattern. RESULTS Sixty-five infants with hypotonia with a mean age of 8 months were enrolled. A deletion was detected in 6 patients by fluorescence in situ hybridization analysis. Only 1 patient had no deletion but had an abnormal methylation pattern. A maternal uniparental disomy was observed in this patient. PWS was diagnosed in 10.7 % (7/65) of the infants with hypotonia. CONCLUSION The prevalence of PWS syndrome is high among infants with hypotonia. PWS should be considered by pediatricians and neonatologists in the differential diagnosis of all newborns with hypotonia. Early diagnosis of PWS is important for the management of these patients.

Cardiac effects of a single course of antenatal betamethasone in preterm infants

Aim: To show the effects of a single course of antenatal betamethasone on cardiac measurements and systolic functions in premature newborn infants. Methods: Seventy six newborn infants with a gestational age of 25–33 weeks were included in the study. They were first classified according to their gestational age: 25–29 weeks (n  =  28) and 30–33 weeks (n  =  48). They were then reclassified as betamethasone positive (mother received one course of betamethasone) or betamethasone negative (mother did not receive any antenatal glucocorticoid treatment). Cross sectional M mode echocardiographic scans were performed during the first three postnatal days and at the end of the first and third weeks. Left interventricular septum (IVS), left ventricular posterior wall (LVPW), left ventricular end diastolic (LVED), and left ventricular end systolic (LVES) dimensions, aortic root (AO), and left atrial diameters (LAs) were measured. The IVS to LVPW ratio was calculated to identify asymmetrical septal hypertrophy. Results: In neither group was any statistically significant difference noted in IVS, LVED, LVES, LVPW, LA, and AO measurements during the three cardiac ultrasonography scans. Systolic function, as assessed by fractional shortening, was not significantly different in infants who received betamethasone antenatally, in either age group. There was no difference in the IVS/LVPW ratios between those who received antenatal steroid and those who did not for the 25–29 week and 30–33 week groups during these three consecutive scans. Conclusion: One course of antenatal betamethasone did not affect the cardiac wall thicknesses and systolic function in premature infants.

A premature newborn with vesiculobullous skin lesions.

Although the rate of congenital syphilis is declining in Western Europe and in the USA, a significant increase is observed in the developing countries. In this contribution, a newborn with cutaneous manifestations of congenital syphilis is presented. Conclusion: Pediatricians should be attentive when confronted with vesiculobullous skin lesions in a newborn, and congenital syphilis should be considered in the differential diagnosis.

The relationship of active ghrelin levels and intrauterine growth in preterm infants

OBJECTIVE We examined the association of active ghrelin levels with birth weight, sex, and gestational age (GA) in small for GA (SGA) and appropriate for GA (AGA) preterm infants. METHODS Active ghrelin levels were measured by ELISA method during the first five postnatal days in 38 preterm SGA infants and 32 preterm AGA controls. RESULTS Active ghrelin levels were significantly higher in preterm SGA infants than in preterm AGA controls (P < 0.01). Active ghrelin levels in preterms with birth weight <1500 g were statistically higher than those over 1500 g. Active ghrelin levels in preterms ≤ 34 gestational weeks were similar to those over 34 weeks. A negative correlation was detected between active ghrelin levels and birth weight (r = -0.561, P < 0.0001) as well as GA (r = -0.449, P < 0.0001). CONCLUSION We found significantly higher active ghrelin levels in SGA preterms than those in AGA preterms and demonstrated a negative correlation between active ghrelin levels and birth weight in preterm infants. This was the first study showing a negative correlation between active ghrelin levels and birth weight in preterm infants.

Macrocephaly-Capillary Malformation Syndrome in a Newborn With Tetralogy of Fallot and Sagittal Sinus Thrombosis

Macrocephaly-capillary malformation syndrome is characterized by cutaneous vascular malformations with associated anomalies as macrocephaly, macrosomia, hemihypertrophy, hypotonia, developmental delay, lax joints, loose skin, polysyndactyly, and neuroimaging abnormalities. We present a newborn with a prenatal diagnosis of macrosomia and tetralogy of Fallot. He also had macrocephaly; a high forehead; capillary hemangioma on the forehead, upper lip, and philtrum; generalized loose skin; postaxial polydactyly of both hands and feet, with neuroimaging findings of polymicrogyria and thrombosis in sagittal sinus and sinus rectus. His condition was diagnosed as macrocephaly-capillary malformation syndrome in the neonatal period and he died suddenly during sleep at 6 months of age. The clinical course in this syndrome is not as benign as was previously thought. Careful follow-up of these patients with particular emphasis on neuroradiologic and cardiologic evaluation might help decrease the risk of sudden death and to improve long-term outcome.

Selective unresponsiveness to HBsAg vaccine in newborns related with an in utero passage of HBV DNA

Abstract Thirty-four out of 158 (22%) newborns to mothers chronically infected by the hepatitis B virus (HBV) did not produce antibodies (Ab) to HBsAg 1 month after the last injection of the HBV vaccine supplemented with HBV specific immunoglobulins. At birth the HBV genome was detected by polymerase chain reaction in the peripheral blood mononuclear cells (PBMC) of a large majority (28 out of 34) of these non-responder newborns but never in the other newborns who responded to the HBsAg vaccine. HBV genome was detected in serum, only in some cases (nine out of 34) and never in absence of HBV DNA in PBMC. For nine out of 14 followed newborns, the absence of response was transitory since anti-HBs Abs appeared after 15 months, without booster, while the HBV had disappeared. Unresponsiveness was specific of the HBV envelope protein since all late responders and 15 months non-responders to the HBsAg vaccine produced normal levels of Abs to the three poliovirus serotypes, to tetanus toxoid and to the pneumococcus polysaccharides. An in utero induced immune tolerance to low doses of HBsAg appears as the most plausible hypothesis to explain this unresponsiveness to HBV vaccine.