Epidemiology of neonatal group B streptococcal disease in the Netherlands before and after introduction of guidelines for prevention.

OBJECTIVES: (1) To describe the epidemiology of neonatal group B streptococcal (GBS) disease over five years (1997-2001) in the Netherlands, stratified for proven and probable sepsis and for very early (<12 h), late early (12 h - <7 days) and late (7-90 days) onset sepsis. (2) To evaluate the effect of the introduction in January 1999 of guidelines for prevention of early onset GBS disease based on risk factors. METHODS: Data on cases were collected in collaboration with the Dutch Paediatric Surveillance Unit and corrected for under-reporting by the capture-recapture technique. RESULTS: Total incidence of proven very early onset, late early onset and late onset GBS sepsis was 0.32, 0.11 and 0.14 per 1000 live births, respectively, and of probable very early onset, late early onset and late onset GBS sepsis was 1.10, 0.18 and 0.02 per 1000 live births, respectively. Maternal risk factors were absent in 46% of the proven early onset cases. Considerably more infants with proven GBS sepsis were boys. 64% of the infants with proven very early onset GBS sepsis were first born compared with 47% in the general population. After the introduction of guidelines the incidence of proven early onset sepsis decreased considerably from 0.54 per 1000 live births in 1997-8 to 0.36 per 1000 live births in 1999-2001. However, there was no decrease in the incidence of meningitis and the case fatality rate in the first week of life. The incidence of late onset sepsis also remained unchanged. CONCLUSION: After the introduction prevention guidelines based on risk factors there has been a limited decrease in the incidence of proven early onset GBS sepsis in the Netherlands. This study therefore recommends changing the Dutch GBS prevention guidelines.

Congenital staphylococcal scalded skin syndrome in a premature infant.

UNLABELLED: A case of congenital staphylococcal scalded skin syndrome (SSSS) with fatal outcome in a premature infant is reported. An intrauterine infection with Staphylococcus aureus was probably the cause for the fulminant course of the disease. Despite adequate antibiotic treatment, the infant died within 24 h after birth because of respiratory failure. CONCLUSION: Although rare, infection may occur in the perinatal period and SSSS may present within the first 24 h of life. In this situation, early administering of appropriate antibiotics is essential.

[Chickenpox in pregnancy with serious consequences for both mother and child]. / Waterpokken bij een zwangere met ernstige gevolgen voor moeder en kind.

A 41-year-old woman with chickenpox in the third trimester of her pregnancy was admitted to the Intensive Care Unit of our hospital for ventilatory support. She was treated with aciclovir, amoxicillin-clavulanic acid and erythromycin. Her baby was delivered by forceps following placental abruption. After delivery, both mother and child recovered slowly but could eventually leave the hospital in good condition. If a pregnant woman without a prior history of varicella-zoster infection is exposed to a child that has chickenpox, passive immunisation with varicella-zoster immunoglobulin should be administered. This reduces the risk of maternal complications and may prevent a fetal varicella syndrome. If the mother has already developed chickenpox and there are serious complications, she should be treated with intravenous aciclovir. If possible, delivery should be delayed until 5 days after the onset of maternal chickenpox.

Microbiological factors associated with neonatal necrotizing enterocolitis: protective effect of early antibiotic treatment.

AIM: The incidence of necrotizing enterocolitis (NEC) strongly increased in an neonatal intensive care unit (NICU) in 1997 and 1998 compared with previous years, which coincided with increased incidence of nosocomial sepsis. Specific risk factors related to this NICU and a possible relationship between NEC and nosocomial sepsis were studied retrospectively, including all patients with NEC since 1990 and matched controls. METHODS: Clinical and bacteriological data from the period before the development of NEC and a similar period for the controls were collected retrospectively and corrected for birthweight and gestational age. Statistical analysis was performed by a stepwise regression model. RESULTS: Data of 104 neonates with NEC and matched controls were analysed. The median day of onset of NEC was 12 d (range 1-63 d). Significant risk factors for NEC were: insertion of a peripheral artery catheter [odds ratio (OR) 2.3, 95% confidence interval (95% CI) 1.3-3.9] and a central venous catheter (OR 5.6, 95% CI 3.1-10.1), colonization with Klebsiella sp. (OR 3.4, 95% CI 1.5-7.5) and Escherichia coli (OR 2.1, 95% CI 1.0-4.5), and the occurrence of sepsis, in particular due to coagulase-negative staphylococci (OR 2.6, 95% CI 1.4-5.1). The risk for NEC was decreased after the early use (< 48 h after birth) of amoxicillin-clavulanate and gentamicin (OR 0.3, 95% CI 0.2-0.6). CONCLUSION: Insertion of central venous and peripheral arterial catheters is positively associated with NEC, as is colonization with the Gram-negative bacilli Klebsiella and E. coli and the occurrence of sepsis, particularly due to coagulase-negative staphylococci. Early treatment with amoxicillin-clavulanate and gentamicin is negatively associated with NEC and may be protective against NEC.

Diagnosis of enterovirus infection in the first 2 months of life by real-time polymerase chain reaction.

During summer and fall, enterovirus infections are responsible for a considerable proportion of hospitalizations of young infants. We prospectively studied the incidence of enterovirus infections via real-time polymerase chain reaction (PCR) in blood, feces, and cerebrospinal fluid samples from infants

Epidemiological survey of neonatal non-polio enterovirus infection in the Netherlands.

The epidemiological, virological, and clinical data of 119 infants less than 30 days of age with enteroviral infection collected from January 1993 to November 1995 by the diagnostic virology laboratories were analyzed retrospectively. Ninety-eight isolates (83%) were obtained in the period of May 1 to December 1 with a peak in the summer months. Sixty-five percent (n = 78) of neonates became ill within the first 2 weeks of life. Echoviruses and Coxsackie virus type B were isolated most frequently, in 77 (65%) and 29 (24%) infants, respectively. Diagnosis was made by viral isolation from stool, nasopharyngeal swab, cerebrospinal fluid, and blood. One hundred four (87%) infants developed fever and 25 (21%) infants had diarrhea. A clinical diagnosis of sepsis was made in 42 (35%) infants and meningitis was diagnosed in 28 (24%) cases. The great majority of sepsis cases (36/86%) occurred in infants less than 15 days of age. In conclusion, non-polio enteroviruses (especially echoviruses) are a common and underreported cause of neonatal infection in the Netherlands in the summer months and are associated with a clinical diagnosis of sepsis or meningitis cases in the first 2 weeks of life in a high proportion of cases.

Prevalence of molecular types and mecA gene carriage of coagulase-negative Staphylococci in a neonatal intensive care unit: relation to nosocomial septicemia.

Molecular typing of isolates revealed that neonatal coagulase-negative staphylococcal (CONS) septicemia is most frequently caused by predominant, antibiotic-resistant CONS types, which are widely distributed among both neonates and staff of the neonatal unit, suggesting cross-contamination. Therefore, infection control measures may be valuable in the prevention of this common nosocomial septicemia.

[Congenital infection: diagnostic serology of the mother not always definitive]. / Congenitale infectie: serologische diagnostiek bij de moeder niet altijd afdoende.

In 2 infants, a girl and a boy, congenital viral infection was diagnosed in the neonatal period. The prenatal examination (serologic investigation for Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus and syphilis (TORCHES)) was negative. In both cases prenatal ultrasonography was abnormal and suggested intrauterine infection. The infants were born with typical symptoms of multisystem disease, known as symptomatic congenital cytomegalovirus infection (jaundice, petechiae, hepatosplenomegaly, intrauterine growth retardation, microcephaly and cerebral calcifications) and congenital rubella syndrome (intrauterine growth retardation, congenital heart disease, cataract, hepatosplenomegaly and cerebral calcifications), respectively. Both had severe cerebral damage. To diagnose severe congenital infection in the first trimester of pregnancy in presence of congenital anomalies in utero there are other possible methods than TORCHES investigation, such as polymerase chain reaction and virus culture in amniotic fluid or in foetal blood obtained by cord puncture.

Perinatal risk factors for cranial ultrasound abnormalities in neonates born after spontaneous labour before 34 weeks.

OBJECTIVE: The aim of this study was to identify risk factors for cranial ultrasound abnormalities in neonates born after spontaneous preterm labour with or without prolonged premature rupture of the membranes (PROM). METHODS: The presence of intraventricular haemorrhage and cystic periventricular leucomalacia was investigated in a cohort of neonates born between 24 and 34 weeks using cranial ultrasound. A stepwise forward logistic regression was performed to analyse the influence of antenatal and postnatal variables on cranial ultrasound abnormalities. RESULTS: The study group consisted of 205 neonates and cranial ultrasound abnormalities were identified in 27 infants. Early onset neonatal infectious disease (OR 3.09, 95% CI 1.24--7.70, P=0.01) increased the risk for cranial ultrasound abnormalities. Gestational age at birth (OR 0.96, 95% CI 0.93--0.99, P=0.03) and a full course of antenatal steroids (OR 0.33, 95% CI 0.13--0.85, P=0.02) reduced the risk for cranial ultrasound abnormalities. CONCLUSION: Early onset neonatal infectious disease is an independent risk factor for cranial ultrasound abnormalities in the very preterm neonate born after spontaneous labour with or without PROM.

Severe neonatal group A streptococcal disease.

UNLABELLED: Since the mid-1980s, an increase in incidence of invasive disease caused by group A streptococci has been noted amongst adults and children; however, neonatal disease is still rare. Between 1979 and 1998, seven neonates with severe group A streptococcal disease were admitted to our neonatal intensive care unit. The clinical presentation, treatment and outcome are described. In three cases of early-onset disease vertical transmission was documented. CONCLUSION: Because the incidence of group A streptococcal disease in the general population seems to have increased over the last two decades, we should be aware of the possibility and particularly the severity of group A streptococcal disease in the neonatal period.

Clinical outcome of cephalothin versus vancomycin therapy in the treatment of coagulase-negative staphylococcal septicemia in neonates: relation to methicillin resistance and mec A gene carriage of blood isolates.

OBJECTIVE: Coagulase-negative staphylococci (CONS) are the most common causative agents in neonatal nosocomial septicemia. Because of widespread methicillin resistance among CONS, empiric therapy with vancomycin is recommended as the primary antibiotic regimen for these infections. In our unit, empiric treatment of nosocomially acquired septicemia consists of cephalothin and gentamicin, which are adjusted subsequently according to the determined bacterial susceptibility profile. Vancomycin is initiated only when the patient has been treated recently with cephalothin or when intravascular lines or endotracheal tube are colonized with oxacillin/cephalothin-resistant CONS strains. The aim of the present study was to evaluate the efficacy of our antibiotic regimen for CONS septicemia, in relation to methicillin-resistance and the carriage of mec A gene, encoding methicillin resistance, among CONS blood isolates from our unit. METHODS: Clinical symptoms of septicemia, clinical outcome, and laboratory parameters of septicemia (C-reactive protein) were studied retrospectively in 66 patients with CONS septicemia. The diagnosis of septicemia was made by the attending neonatologist and was defined by clinical symptoms of septicemia in the presence of a positive finding of a blood culture test, which was performed using a defined protocol. All CONS blood isolates were included to determine mec A gene carriage. RESULTS: In the 66 patients, three treatment categories were distinguished: treatment with cephalothin (25 patients, 38%); with vancomycin (15 patients, 23%); and primary treatment with cephalothin, switched subsequently to vancomycin (26 patients, 39%). It was found that 92% of all CONS blood isolates (61/66) were mec A-positive. Concordance of mec A gene carriage with methicillin/oxacillin resistance was found in 56 of 66 isolates (85%); 10 of 61 (16%) isolates that were mec A-positive were determined as oxacillin-susceptible. Although 22 of the 25 blood isolates of the cephalothin-treated patients were mec A-positive, clinical recovery was uneventful. In the 26 patients in whom antibiotic therapy was switched from cephalothin to vancomycin, two strains were cephalothin-susceptible and 8 patients already had recovered clinically before the switch, which was based solely on susceptibility test results. CONCLUSIONS: Cephalothin was found to be clinically efficacious in the treatment of neonatal CONS septicemia, despite a steadily increasing mec A gene carriage of CONS blood isolates in our neonatal intensive care unit and a corresponding high methicillin/oxacillin resistance. Hence, cephalothin remained the antibiotic of first choice in the treatment of CONS septicemia in our unit, with vancomycin selected exclusively for cases not responding to initial cephalothin treatment, or for patients developing CONS septicemia during or after recent cephalothin treatment. By applying this approach in our unit, we were able to reduce vancomycin use from 62% in 1994 to 1995 to 21% in 1997. This shows that such a policy may result in an important reduction of vancomycin use, which may aid in postponing the threatening emergence of vancomycin resistance among Gram-positive cocci.

Antibody responses and opsonic activity in sera of preterm neonates with coagulase-negative staphylococcal septicemia and the effect of the administration of fresh frozen plasma.

Coagulase-negative staphylococcal septicemia is the most prominent nosocomial infection in neonatal intensive care units. Immaturity of host defenses in premature neonates is assumed to constitute an important risk factor. Opsonophagocytosis is considered to be the key host defense system against staphylococci with IgG antibodies as a major opsonin. For this reason we have studied serum IgG antibody titers and opsonic activity to coagulase-negative staphylococci in 20 infants with septicemia and 40 matched control subjects. In addition, we assessed the effect of administration of fresh frozen plasma (FFP) on IgG antibody titer and serum opsonic activity in 12 patients with septicemia. IgG antibodies, quantified by ELISA and opsonic activity, determined by flow cytometry, were expressed as a percentage of the value of pooled normal human reference serum. Both patients and control subjects showed low IgG titers (median, 21%; range, 1-192%) and a low opsonic activity (median, 33%; range, 8-484%) at birth. During the first 2 postnatal wk IgG titers decreased significantly in septicemia patients (from a median of 30 to 17%, p = 0.025), but not in control subjects, whereas opsonic activity remained unchanged. The titer of IgG antibodies increased significantly in septicemia patients after FFP administration (from a median of 17 to 41%, p = 0.002), whereas the effect on opsonic activity was unpredictable, showing a moderate increase in 10 out of 12 infants, and in 2 patients even a substantial decrease (>50%), despite adequate opsonic activity in the corresponding FFP batches. Immunoblotting of sepsis isolates with the corresponding patient sera demonstrated that septicemic infants may generate IgG antibodies against their blood isolate. Neonates who acquire coagulase-negative staphylococcal septicemia cannot be distinguished from control subjects on the basis of IgG antibodies and opsonic activity to staphylococci either at birth or during the first 2 postnatal wk. The administration of FFP to septicemia neonates has an unpredictable effect on opsonic activity and therefore does not seem to be a useful addition to antibiotic therapy.

Ten-year neonatal hepatitis B vaccination program, The Netherlands, 1982-1992: protective efficacy and long-term immunogenicity.

From 1982 to 1989, 705 infants born to HBsAg-positive mothers entered the Dutch neonatal hepatitis B vaccination program and received passive-active hepatitis B immunization in three randomized controlled trials testing variations in time of starting active vaccination, dose and type of vaccine, and number of hepatitis B immunoglobulin (HBIg) injections. A meta-analysis of individual patient data of the three randomized trials was performed to determine which independent host and vaccination related factors influence protective efficacy and long-term immunogenicity, and to assess whether hepatitis B vaccination concomitant with standard DKTP vaccination provides optimal protection. Statistical methodology included multivariate logistic regression analysis. Eight infants (1.1%), all born to HBeAg-positive mothers, became HBsAg carriers within the first year of life. The protective efficacy rate (PER) of passive-active immunization at 12 months follow-up was 92% for the total group of children from 114 HBeAg-positive mothers with no significant differences between children starting active immunization at birth or at 3 months of age, between infants starting at 3 months of age receiving one or two doses of HBIg or between those receiving plasma derived or recombinant vaccine. The only factor that affected the PER significantly was the level of maternal HBV DNA; PER was 100% if maternal HBV DNA was < 150 pg ml-1 and 68% for HBV DNA levels > 150 pg ml-1. After 5 years of follow-up, the group that started active immunization at birth had significantly more infants with loss of seroprotection (anti-HBs levels < 10 IU l-1, 15%) than the corresponding group starting at 3 months of age (anti-HBs < 10 IU l-2, 2%). One of 35 children with loss of seroprotection at 2 years became a HBsAg carrier in the fifth year of follow-up. This meta-analysis shows that the protective efficacy of passive-active hepatitis B vaccination is mainly influenced by material HBV DNA levels, and independent of the time of starting active vaccination at birth or at 3 months of age; long-term immunity was enhanced by starting active vaccination concomitant with DKTP vaccination. These findings allow incorporation of hepatitis B vaccine into the standard infant immunization programs for countries with a passive-active immunization strategy for the control of hepatitis B. Additional measures are needed to protect neonates of highly viremic women.

Sonographic determination of the position of the conus medullaris in premature and term infants.

We determined the position of the conus medullaris (CM) relative to the vertebral column in premature and term babies and assessed its ascent in 99 children, using ultrasound. We related level to the middle of a vertebral body or an intervertebral space. Postmenstrual age at examination was related to the level of the CM with the Krus-kal-Wallis test. The children were divided into five age groups and the level of the CM was analysed with a chi-squared test. An increase in postmenstrual age was significantly associated with higher levels of the CM (P = 0.003). The CM ascended in the older children (P = 0.04). The CM is at the L2/L3 intervertebral space in premature babies of 27-29 weeks of postmenstrual age. In babies of more advanced gestation a statistically significant ascent of the CM is observed and the CM is at the adult level of the L1/L2 intervertebral space around the 40th postmenstrual week. No further ascent occurs thereafter.

Development of resistance to aminoglycosides among coagulase-negative staphylococci and enterobacteriaceae in a neonatal intensive care unit.

A prospective study of the development of resistance to aminoglycosides among coagulase-negative staphylococci (CNS) and Enterobacteriaceae (ENT) was conducted for all patients admitted to a neonatal intensive care unit (NICU) from October 1985 to January 1990. A change in antibiotic regimen from gentamicin to amikacin occurred in January 1986, due to widespread gentamicin resistance among CNS, the most important cause of nosocomial infections in this NICU. From 657 patients, 884 faecal cultures, 1505 cultures from the respiratory tract and 152 blood cultures were included in the study. After its introduction, susceptibility to amikacin decreased rapidly in faecal and respiratory CNS isolates (from 62% to 28% and from 58% to 23% respectively). During the first half year, resistance to amikacin in faecal CNS isolates developed more rapidly among antibiotic-treated patients than among patients not treated with antibiotics. Susceptibility to amikacin in CNS blood isolates decreased more slowly, from 94% to 58% in 1987, while subsequently an increase in susceptibility was observed to about 80% in 1989. The same difference in development of resistance in faecal and respiratory CNS isolates compared to CNS blood isolates was noticed for gentamicin and tobramycin. In contrast, ENT remained highly (85-100%) susceptible to amikacin, gentamicin and tobramycin throughout the study period. It was concluded that four years after its introduction amikacin still appeared to be a valuable antibiotic in combination treatment of the vast majority of clinically important infections occurring in our NICU, since both Enterobacteriaceae and the majority of CNS blood isolates proved to be susceptible to this agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Chylothorax in the neonatal period.

Chylothorax is defined as an effusion of lymph in the pleural cavity. In the neonate both congenital and traumatic (iatrogenic) forms exist. Birth asphyxia and respiratory insufficiency are major symptoms of congenital chylothorax, requiring resuscitation and artificial ventilation. Antenatal diagnosis by ultrasound allows early therapeutic intervention such as ventilatory support and drainage of chylous fluid immediately after birth. Traumatic chylothorax is mainly seen after intrathoracic surgery. Treatment primarily consists of continuous or intermittent drainage of chyle with replacement of fluid-, electrolyte-, and protein losses and parenteral nutrition. Introduction of oral feeding is considered only after a substantial period without chyle production in the pleural cavity and consists of a medium-chain triglyceride containing formula. In a minority of cases surgical intervention is necessary.

[Diagnosis of infection in full-term infants born after prolonged status of ruptured membranes: clinical observation is sufficient]. / Infectiediagnostiek bij à terme pasgeborenen na langdurig gebroken vruchtvliezen: klinische observatie is voldoende.

We retrospectively studied our strategy in 80 full-term newborns, born more than 24 hours after rupture of amniotic membranes. Six patients developed clinical signs of sepsis, in four of them sepsis was proven by a positive blood culture. In all cases, clinical symptoms were the first sign of infection. Routine laboratory tests (CRP, leucocyte counts and differentiation, thrombocyte counts) and microbiological investigations (surface cultures, cord blood cultures) were not helpful for the diagnosis of infection at an early stage. These findings are in accordance with the literature. We conclude that after prolonged rupture of membranes with full-term newborns postnatal paediatric care can be limited to a close observation period of 48 hours. There is no need for any further routine investigation of infants without clinical signs of infection.