Changes in the incidence and epidemiology of neonatal group B Streptococcal disease over the last two decades in Crete, Greece.

Group B streptococcus (GBS) remains a leading cause of neonatal disease. However, GBS rates and prevention strategies vary considerably worldwide. Herein, we investigated the burden and epidemiological trends of neonatal GBS infections in our area (Greece) over the last two decades. We conducted a multicenter retrospective study that includes all cases of culture-proven GBS disease in infants <90 days old in the last 22 years. Neonatal GBS incidence was 0.17/1000 live births (95%CI: 0.11-0.21). A significant increase was noted during the second decade (0.23 vs 0.10/1000, P<0.05). Late onset disease (LOD) significantly increased during the second decade (0.08 vs 0.02, P<0.05). Infants in the LOD group had a higher risk of meningitis (RR 1.8, 95%CI: 1.23-2.71). Long-term neurological sequelae were reported in 42.8% of meningitis cases. The mortality rate was 8%. The incidence of neonatal GBS disease in our area is among the lowest reported, but an increase was noted the last decade mainly due a rise in the LOD. The burden of LOD, the mortality and long-term disability are still substantial, thus effective prevention strategies - including maternal vaccination for neonatal GBS - are needed.

Quantitative ultrasound measurements in premature infants at 1 year of age: the effects of antenatal administered corticosteroids.

The aim of this study was to evaluate the effects of antenatally administered glucocorticoids on bone status of preterm infants at 1 year corrected age. The study population consisted of 32 preterm infants with a gestational age of 24-34 weeks. The infants were divided into two groups according to antenatal exposure to corticosteroids. Quantitative ultrasound (QUS) assessment of bone was performed in the study infants at the corrected age of 1 year. Blood levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP) were measured at birth and at 1 year corrected age. Levels of PICP and ICTP were significantly lower at birth in corticosteroid-exposed neonates (P < 0.05). At corrected age of 12 months ICTP levels remained significantly lower in corticosteroid-exposed infants, but we found no significant difference in levels of the bone-formation marker PICP between corticosteroid-exposed and nonexposed infants. In the majority of participant preterm infants bone speed of sound (SOS) was within age-adjusted normal values of full-term infants. There was no significant difference in bone SOS between exposed and nonexposed infants at corrected age of 12 months. There was no correlation between SOS and levels of bone markers. The results of our study indicate that, despite the suppression of fetal bone turnover at birth in corticosteroid-exposed infants, antenatal glucocorticoid treatment seems to have no long-term impact on bone status of preterm infants assessed by QUS complementary to measurement of bone-turnover markers at 1 year corrected age.

Circulating concentrations of α- and ß-chemokines in neonatal sepsis.

BACKGROUND: Despite advances in neonatal care, sepsis remains a threat, in particular for premature neonates, due to immature immunologic defense. Deficient chemotaxis, an essential process in the host response to pathogens, may contribute to this vulnerability. In this study we investigated chemokine expression in septic premature and term neonates. METHODS: Seventy-one neonates with signs and symptoms suggestive of systemic infection, requiring full sepsis evaluation and treatment, formed the study group; 58 neonates without sepsis served as the control group. Serum concentrations of two α-chemokines (GRO-α and ENA-78) and two ß-chemokines (RANTES and MIP-1α) were measured at day 0 and day 3-5 of infection in the study group, and on the day of inclusion in the study in the control group. RESULTS: During infection, serum levels of GRO-α in the study group were higher and serum levels of RANTES were lower as compared to those of the control group (p<0.001 and p<0.001, respectively). Furthermore, levels of GRO-α were higher and levels of RANTES were lower on day 0 as compared to levels on day 3-5 (p<0.001 and p<0.001, respectively). Chemokine serum concentrations on day 3-5 in the study group did not differ significantly as compared to those of the control group. Term and preterm infants seemed to respond similarly regarding chemokine expression. No significant differences were found in serum levels of MIP-1α and ENA-78. CONCLUSIONS: Our findings suggest up-regulation of GRO-α and down-regulation of RANTES at the onset of a septic episode, similar to the response pattern observed in septic adults. Both term and preterm neonates appear to have the potential to elicit a chemotactic response to infection.

Risk factors for periventricular leukomalacia.

OBJECTIVE: To identify risk factors implicated in the development of periventricular leukomalacia (PVL) and to evaluate the possible association between PVL with neonatal morbidity. DESIGN: Retrospective case control study. SETTING: Medical records of neonates admitted to a University Hospital between January 2000 and December 2005. POPULATION: Sixty-nine neonates with PVL born at gestational ages from 24 to 34 weeks. Forty-three of these had a cystic form of PVL (cPVL), whereas 26 had transient periventricular echodensities (PVE). METHODS: Each case was matched for gestational age and year of birth with one control. The maternal and neonatal medical records were searched. All data was compared between cases with PVL and controls, as well as between cases with cPVL and those with PVE. Stepwise logistic regression analysis was conducted to identify the independent predictors of PVL. RESULTS: Neonates with PVL suffered more frequently from intraventricular hemorrhage (IVH), respiratory distress syndrome type I (RDS I), seizures, sepsis, required more days of both mechanical ventilation and oxygen administration, while the duration of their hospitalization was longer compared to controls. Also, they were born more frequently to mothers who suffered from preterm premature rupture of membranes (PPROM) and clinical chorioamnionitis. We found that male gender, PPROM, preeclampsia, hypocarbia and IVH were independently associated with PVL. CONCLUSIONS: This study revealed that preterm neonates born to mothers with PPROM or preeclampsia, as well as neonates who presented with hypocarbia or suffered from IVH, appeared to be at high risk for the development of PVL.

Outcome of toxoplasmosis acquired during pregnancy following treatment in both pregnancy and early infancy.

OBJECTIVES: Congenital toxoplasmosis is associated with clinical dilemmas as untreated infants may have a guarded prognosis and as treatment may induce severe side effects. The aim of this study was to investigate the outcome of infants born to mothers with toxoplasmosis acquired during pregnancy, following administration of appropriate regimens both during pregnancy and early infancy. STUDY DESIGN: All 35 infants, born to mothers with toxoplasmosis acquired during pregnancy, and referred to the major Neonatal Department in Crete, Greece, during the 7-year period 1997-2003 were included. All neonates were evaluated soon after birth and on a regular follow-up. RESULTS: Almost all mothers received spiramycin from diagnosis through labor and 2 received pyrimethamine and sulfadiazine. At birth, infants had IgG antibody titers ranging from 1/1,350 to 1/109,350. All infants initially received pyrimethamine, sulfadiazine and folinic acid but in only 4 cases treatment was continued beyond the second month of life. Transient neutropenia was commonly observed. A follow-up period of 1.2-8.2 years did not reveal any remarkable sequelae. CONCLUSIONS: Our findings suggest that effective treatment both during pregnancy and early infancy is safe and may contribute to a good outcome of infants born to mothers with toxoplasmosis acquired during pregnancy.

Methicillin-resistant Staphylococcus aureus osteomyelitis and septic arthritis in neonates: diagnosis and management.

Acute osteomyelitis (AO) in neonates, although rare, represents a diagnostic and therapeutic challenge. A high index of suspicion is necessary to make an early diagnosis, and the observation of clinical signs is crucial. The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is an emerging problem in pediatrics. In neonates, MRSA infections can cause a wide spectrum of diseases including bone and joint infections. We report two cases of AO in full-term neonates, with no risk factors, due to MRSA.

Levels of bone collagen markers in preterm infants: relation to antenatal glucocorticoid treatment.

Although the beneficial effects of antenatally administered glucocorticoids are well documented, data on the potential of adverse consequences are limited. The objective of this study was to determine the effects of antenatally administered glucocorticoids on biochemical markers of bone metabolism of 55 preterm infants with a gestational age of 24-34 weeks who were enrolled in the study. Neonates were divided into two groups according to antenatal exposure to corticosteroids. There were no significant differences between the groups in clinical characteristics and anthropometric variables. We studied blood levels of osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) at the time of delivery, on postnatal day 10, and at 2 and 4 months of life. Comparing the groups, we found statistically significant reduction in PICP levels at birth in corticosteroid-exposed neonates (P < 0.05). The levels of bone markers increased progressively on the first days of life. There were no significant differences between groups in bone markers at 10 days or at 2 and 4 months of life. We found no significant difference for bone markers between groups of infants exposed to single or repeated maternal corticosteroid treatments. In summary, antenatal glucocorticoid treatments are suggested to have a negative impact on fetal bone formation as reflected by low PICP levels at birth. However, this negative effect on bone markers seems to be a temporary effect that subsides on the first days of life and afterward.

Use of recombinant erythropoietin for the management of severe hemolytic disease of the newborn of a K0 phenotype mother.

Very few people do not express any Kell antigens on their red blood cells (K0 phenotype). They can be immunized by transfusion or pregnancy and develop antibodies against Kell system antigens. These maternal antibodies can cause severe hemolytic disease of the fetus/newborn, as a result of the suppression of erythropoiesis and hemolysis. Multiple intrauterine transfusions in the management of severe hemolytic disease have been shown to cause erythropoietic suppression as well. Recombinant erythropoietin has been successfully used in the management of late anemia of infants with Rh hemolytic disease and in 1 case of KEL1 (Kell)-associated hemolytic disease. The authors present the case of severe hemolytic disease of a newborn due to KEL5 (Ku) isoimmunization of his K0 phenotype mother. Regular intrauterine transfusions were performed to manage the severe fetal anemia (Hb 3 g/dL). A male infant was born at the 36th week of gestation having normal hemoglobin (15.8 g/dL) and developed only mild hyperbilirubinemia. On the 15th day of life, the infant's hematocrit had fallen to 27.3%, with low reticulocyte count and low erythropoietin level. The infant was managed successfully with recombinant erythropoietin.

Interleukin-6 in preterm premature rupture of membranes as an indicator of neonatal outcome.

BACKGROUND: The aim of this study was to investigate whether the levels of interleukin-6 (IL-6) can be used as markers of adverse outcome in preterm neonates born after preterm premature rupture of membranes (PPROM). METHODS: This study involved 109 preterm neonates and their mothers. The PPROM group consisted of 58 neonates who were born after PPROM, and the control group consisted of 51 neonates. IL-6 levels were measured in umbilical cord blood, maternal blood sampled during delivery and in neonatal blood taken on the fourth day of life. RESULTS: In the PPROM group, IL-6 concentrations in maternal blood, cord blood, and neonatal blood were significantly higher in neonates with sepsis, compared with those without sepsis (P < 0.001). Choosing 108.5 pg/ml as a cut-off concentration of IL-6 in umbilical cord blood for neonatal sepsis resulted in sensitivity 95%, specificity 100%, positive predictive value 100%, and negative predictive value 97.4%. Concerning IL-6 in maternal blood, a cut-off concentration of 81 pg/ml showed sensitivity 90%, specificity 97.4%, positive predictive value 94.7%, and negative predictive value 94.9%. Eighteen of 20 neonates with early sepsis and seven of nine neonates, who died in the PPROM group, were born of mothers with IL-6 levels above the cut-off concentration in their blood during delivery. CONCLUSIONS: IL-6 in umbilical cord blood was the most significant variable for predicting early onset sepsis in preterm neonates. IL-6 in maternal blood was indicative of intrauterine environmental threats and might be used to identify pregnancies where intervention would be appropriate.

Perinatal outcome of twin pregnancies after in vitro fertilization.

BACKGROUND: There are conflicting data concerning perinatal outcome of twin, in vitro fertilization (IVF) pregnancies. The aim of this study was to evaluate and compare perinatal and neonatal outcomes in twin IVF pregnancies to those of spontaneously conceived twin gestations. METHODS: The medical files of 73 IVF and 148 naturally conceived twin pregnancies were studied retrospectively. Data concerning maternal characteristics, obstetric complications, and neonatal outcome were recorded and compared by chi2 test. The one-way analysis of variance (anova) was used to compare the means of groups. RESULTS: Mean maternal age, the proportion of nulliparous women, and the incidence of premature rupture of membranes, cesarean section, and premature delivery were significantly higher in the study group. The mean birthweight was significantly lower, the frequency of admission to the intensive care unit and the duration of hospitalization were significantly higher in the study group. The incidence of intraventricular hemorrhage was significantly higher in the IVF group. The number of perinatal deaths was similar. CONCLUSION: IVF twin pregnancies are at greater risk for obstetric complications and adverse neonatal outcome in comparison with naturally conceived twin gestations.

Significance of hypocarbia in the development of periventricular leukomalacia in preterm infants.

BACKGROUND: Despite rapid advances in the management of preterm infants, periventricular leukomalacia (PVL) remains a considerable problem in neonatal intensive care. The aim of this study was to determine whether hypocarbia is associated with the development of PVL in mechanically ventilated, preterm infants and to emphasize the importance of avoiding this disturbance. METHODS: The authors evaluated 52 mechanically ventilated infants with a gestational age of <34 weeks, who exhibited hypocarbia in the first three postnatal days (lowest carbon dioxide tension being <25 mmHg). These infants were then compared with 52 infants in a control group not exhibiting hypocarbia, matched for birthweight and gestational age. A diagnosis of PVL was made on the basis of the results of cranial ultrasonography. Confounding factors potentially associated with the development of PVL were controlled in logistic regression analyses. RESULTS: Of the 52 mechanically ventilated preterm infants with hypocarbia, 10 (19.2%) developed cystic PVL, and six (11.5%) developed periventricular echodensity. Of the 52 infants in the control group only two (3.8%) developed cystic PVL, and one (1.9%) infant developed periventricular echodensity. The authors observed no significant differences in other prenatal and perinatal risk factors between the two groups. CONCLUSION: Hypocarbia in mechanically ventilated preterm infants during the first days of life is suggested as being an independent predictor of PVL, predisposing these infants to subsequent neurodevelopmental delay.

Feeding difficulties in a neonate with primary cricopharyngeal achalasia treated by cricopharyngeal myotomy.

Primary cricopharyngeal achalasia resulting from failure of relaxation of the cricopharyngeus muscle is a rare but significant cause of dysphagia in newborns. Symptoms may be nonspecific. Although surgical management with cricopharyngeal myotomy has been employed successfully for the treatment of this disorder, swallowing difficulties may persist postoperatively, probably due to association with other esophageal abnormalities. Alternative methods of feeding may be required to ensure adequate nutrient intake. We report the case of a full-term, 2-day-old neonate with this rare clinical condition, treated by myotomy, in whom swallowing difficulties persisted for several weeks after surgery. Satisfactory nutrition was maintained postoperatively with the support of a nasogastric feeding tube until improvement in feeding intolerance. Complete symptomatic relief was attained at the age of 5 months.

Eosinophilia in sick neonates.

Eosinophilia is common in the neonatal period. However, its causes, pathomechanism and clinical significance are still unknown. Previous reports have described that eosinophilia may be associated with numerous conditions (establishment of an anabolic state, drug reactions, response to foreign antigens, chronic lung disease, erythropoietin treatment and infections). The aim of this study was to evaluate the possible association of various conditions, especially infection, with eosinophilia and to clarify whether recognition of increase in eosinophil count is of any clinical significance in the management of a sick neonate. Fifty-six neonates with eosinophilia (absolute eosinophil count > 700/mm3) and 55 control neonates matched for gestational age, birth weight and hospitalization days were included in the study. A significant difference between the two groups was found only in blood transfusions, immuno-globulin treatment, specific antibiotic treatment and infectious disease. However, neonates who develop sepsis and are treated with antibiotics and immuno-globulin are more often transfused. It can thus be concluded that the main relationship observed is between eosinophilia and infection whereas the other associations are secondary. The relative risk factor for infection when the absolute eosinophil count is > 700/mm3, is 1.58, with a confidence interval 1.30-1.91. Eosinophilia seems to be a reliable indicator of sepsis while normal absolute eosinophil count does not exclude infection. Infection should be strongly considered in the evaluation of a sick neonate with eosinophilia.

Peroneal nerve palsy: a complication of umbilical artery catheterization in the full-term newborn of a mother with diabetes.

Umbilical artery catheters are an essential aid in the treatment of newborn infants who have cardiopulmonary disease. However, it is well-known that umbilical artery catheterization is associated with complications. The most frequent visible problem in an umbilical line is blanching or cyanosis of part or all of a distal extremity or the buttock area resulting from either vasospasm or a thrombotic or embolic incidence. Ischemic necrosis of the gluteal region is a rare complication of umbilical artery catheterization. We report the case of a full-term infant of an insulin-dependent diabetic mother with poor blood glucose control who developed a left peroneal nerve palsy after ischemic necrosis of the gluteal region after umbilical artery catheterization. The infant was born weighing 5050 g. The mother of the infant had preexisting diabetes mellitus that was treated with insulin from the age of 14 years. The metabolic control of the mother had been unstable both before and during the pregnancy. The neonate developed respiratory distress syndrome soon after birth and was immediately transferred to the neonatal intensive care unit. Mechanical ventilation via endotracheal tube was quickly considered necessary after rapid pulmonary deterioration. Her blood glucose levels were 13 mg/dL. A 3.5-gauge umbilical catheter was inserted into the left umbilical artery for blood sampling without difficulty when the infant required 100% oxygen to maintain satisfactory arterial oxygen pressure. Femoral pulses and circulation in the lower limbs were normal immediately before and after catheterization. A radiograph, which was taken immediately, showed the tip of the catheter to be at a level between the fourth and fifth sacral vertebrae. The catheter was removed immediately. Circulation and femoral pulses were normal and no blanching of the skin was observed. Another catheter was repositioned and the tip was confirmed radiologically to be in the thoracic aorta between the sixth and seventh thoracic vertebrae. The catheter was continuously flushed with heparinized solution. Three days after umbilical arterial catheterization, bruising was observed over the left gluteal region. The catheter was immediately removed despite its correct position. Over the next few days, the bruised skin and underlying tissues became necrotic. The area affected was 3 x 4 cm in diameter, with central necrosis surrounded by a rim of dark, red skin, which, in turn, was sharply demarcated from normal skin by a narrow, pale zone. Surgical excision of the gluteal necrosis was performed, but a deep ulcer 3 cm in diameter was left. The gluteal ulcer required 1 month to heal completely with extensive scar tissue formation. Throughout this period, the infant showed active movements in all of her limbs. At 4 weeks of age deterioration of all movement below the left knee with a dropping foot was observed. Severe peroneal nerve palsy was confirmed through nerve conduction studies, and there was electromyographic evidence of degeneration of the muscles supplied by the peroneal branch of the sciatic nerve. A Doppler study, which was also conducted, revealed no vascular damage. Treatment with physiotherapy and night-splinting of the left ankle was instituted. Repeated examination and nerve conduction tests at 3 months showed slow improvement with the left peroneal nerve remaining nonexcitable. At the time of this writing, the infant is 6 months old, and muscular strength below the left knee is still weak and atrophic changes in the form of muscle-wasting are already present. The rest of her motor development is normal. In our case, gangrene of the buttocks and sciatic nerve palsy followed displacement of the tip of the catheter into the inferior gluteal artery, a main branch of the internal iliac artery supplying the gluteus maximus, the overlying skin, and the sciatic nerve. The gangrenous changes were probably caused by vascular occlusion resulting from catheter-induced vasospasm of the inferior gluteal artery. Sciatic nerve palsy associated with umbilical artery catheterization has been postulated to be caused by vascular occlusion of the inferior gluteal artery. Infants of diabetic mothers may exhibit changes in coagulation factors and be at increased risk of thrombotic complications in utero and postnatally. In addition, maternal diabetes mellitus is associated with an increased incidence of congenital abnormalities, the incidence of which is 3 to 5 times higher than that among nondiabetic mothers. Although no particular or specific abnormalities have been associated with maternal disabilities, abnormalities of the cardiovascular system, including the development of umbilical vessels, frequently occur. This complication of umbilical artery catheterization has not been widely reported. We describe the first case that refers to gluteal gangrene and peroneal nerve palsy after umbilical artery catheterization of a newborn infant of a diabetic mother with poor blood glucose control. It should be noted that there were no contributing factors except that of the displacement of the catheter into the inferior gluteal artery. We speculate that the displacement of the tip of the catheter, with no difficulty in the present case, was associated with the maldevelopment of normal branching patterns of arteries after exposure of the fetus to hyperglycemia. In conclusion, umbilical artery catheterization is possibly associated with vascular occlusion, particularly in infants of diabetic mothers. Frequent inspection after the procedure has been performed is of the utmost importance especially in these neonates who often suffer from cardiopulmonary disease and require catheterization of their umbilical artery.