Licia Lugli

Group B Streptococcus Late-Onset Disease: 2003–2010

BACKGROUND: There is insufficient population-based data on group B streptococcus (GBS) late-onset disease (LOD). Risk factors and routes of GBS transmission are poorly understood. METHODS: A prospective, cohort study was conducted to collect incidence data on LOD and evaluate GBS infections over an 8-year period (2003–2010). Starting from January 2007, maternal rectovaginal and breast milk cultures were routinely collected on confirmation of the LOD diagnosis to assess maternal GBS culture status. RESULTS: The incidence rate of LOD was 0.32 per 1000 live births (1.4 and 0.24 per 1000 live births for preterm and term newborns, respectively). The registered cases of LOD (n = 100) were classified as sepsis (n = 57), meningitis (n = 36), or focal infection (n = 7). Thirty neonates were preterm (2 had recurrent infection); 68 were term. Four infants died (3 early preterm, 1 term). At the time the LOD diagnosis was confirmed, 3 (6%) of 53 mothers had GBS mastitis, and 30 (64%) of 47 carried GBS at the rectovaginal site. Early (7–30 days) LOD presentation was associated with neonatal brain lesions or death (odds ratio: 0.96 [95% confidence interval: 0.93–0.99]). Intrapartum antibiotic exposure was significantly associated with mild (12 of 22) rather than severe (11 of 45; P = .03) LOD. CONCLUSIONS: Preterm neonates had the highest rates of LOD and mortality. Most mothers carried GBS at the time of the LOD diagnosis, whereas 6% had mastitis. Intrapartum antibiotics were associated both with delayed presentation of symptoms and milder LOD.

Group B Streptococcal Infections in a Northern Region of Italy

BACKGROUND. Group B streptococcus is a leading cause of neonatal bacterial infections. Despite adoption of preventive strategies, cases of infection continue to occur and there is concern that widespread antimicrobial prophylaxis might delay rather than prevent disease onset, increasing the rates of late-onset diseases. OBJECTIVES. The purpose of this study was to determine the incidence and clinical features of early- and late-onset group B streptococcus disease in a northern region of Italy where a screening-based approach had been proposed. METHODS. A population-based study was prospectively conducted in Emilia-Romagna, Italy. Infections that occurred during 2003–2005 in infants aged <3 months were analyzed. RESULTS. Among 112933 live births, 56 cases of invasive disease (30 early- and 26 late-onset disease) were observed, giving an annual group B streptococcus disease incidence of 0.50 per 1000 live births. Eleven infants with early-onset disease showed no signs of illness or were mildly ill, whereas 19 had moderate-to-severe symptoms, and culture-proven meningitis was found in 2. Risk factors were detected in 12 women. Twenty-two mothers had antenatal screening; 5 were group B streptococcus colonized, but 17 were culture-negative. Prophylaxis was administered in 3 women. Three infants with late-onset diseases were mildly ill, whereas 23 had moderate-to-severe symptoms. Risk factors were found in 7 mothers. Late-onset diseases were clinically more severe than early-onset diseases; meningitis was diagnosed in 12 infants, and 4 of 26 died. CONCLUSIONS. The incidence of early-onset disease was low. Some early infections were still observed because of negative screening results or missed opportunity for prevention. Late-onset diseases accounted for most meningitis cases and deaths. Strict adherence to protocols and adoption of optimal culture methods would further improve prevention of early-onset disease, but the aim of future strategies should be the prevention of all invasive diseases.

Group B Streptococcus early-onset disease in Emilia-Romagna: review after introduction of a screening-based approach.

Background: Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections. Early-onset infections have decreased in recent years but, despite considerable efforts poured into prevention, cases continue to occur. Objectives: To analyze trends and identify determining factors for the persistence of the GBS infections. To evaluate the impact of antenatal screening and intrapartum chemoprophylaxis on the clinical presentation of the infection. Methods: A prospective cohort, population-based study has been ongoing in Emilia-Romagna (Italy) since 2003. Invasive GBS infections, observed between 2003 and 2008 in infants aged <7 days were analyzed. Results: Among 214,120 live births, 61 early-infections were observed. Fourteen infants (23.0%) were born preterm. Among 47 infants who were delivered at term, 28 were born to mothers who had no risk factors and 7 were born to mothers who had none other than GBS colonization. Forty-one women at term had been screened prenatally; among them, only 10 were documented as GBS culture-positive. Disease severity was highest in infants at lower gestational ages, but most meningitis cases were observed in term infants born to mothers who were GBS culture-negative at screening. Nine newborns had culture-proven infection despite having received intrapartum antibiotics. They were born to mothers with ≥1 obstetrical risk factors and 5 mothers had been treated during labor with macrolides. Conclusion: Most infections presented in infants whose mothers had been screened as GBS culture-negative. Missed opportunities for prevention contributed more than prophylaxis failures to the early-onset disease burden.

Preterm birth and developmental problems in the preschool age. Part I: minor motor problems

Nearly half of very preterm (VP) and extremely preterm (EP) infants suffers from minor disabilities. The paper overviews the literature dealing with motor problems other than cerebral palsy (CP) during infancy and preschool age. The term “minor motor problems” indicates a wide spectrum of motor disorders other than CP; “minor” does not mean “minimal”, as a relevant proportion of the preterm infants will develop academic and behavioural problems at school age. Early onset disorders consist of abnormal general movements (GMs), transient dystonia and postural instability; these conditions usually fade during the first months. They were underestimated in the past; recently, qualitative assessment of GMs using Prechtl’s method has become a major item of the neurological examination. Late onset disorders include developmental coordination disorder (DCD) and/or minor neurological dysfunction (MND): both terms cover partly overlapping problems. Simple MND (MND-1) and complex MND (MND-2) can be identified and MND-2 gives a higher risk for learning and behavioural disorders. A relationship between the quality of GMs and MND in childhood has been recently described. The Touwen infant neurological examination (TINE) can reliably detect neurological signs of MND even in infancy. However, the prognostic value of these disorders requires further investigations.

Impact of perinatal practices for early-onset group B Streptococcal disease prevention

Background: Prevention of residual cases of neonatal group B streptococcus (GBS) early-onset disease (EOGBS) has become a goal in the past decade. This study is aimed at evaluating changes in the incidence of EOGBS over a 9-year period after the implementation of a screening-based approach and comparing 2 different protocols for managing healthy-appearing at-risk newborns (ARNs). Methods: A screening-based strategy was introduced in Emilia-Romagna (Italy) in 2003. A prospective, cohort study was conducted from 2003 to 2011; culture-proven EOGBS cases were analyzed in 2 periods: period 1 (2003 to 2008) and period 2 (2009 to 2011). ARNs (≥35 weeks’ gestation) were managed according to 2 different protocols: laboratory testing plus observation (period 1) was replaced with expectant observation alone (period 2). Results: Ninety-one EOGBS cases were observed (incidence rate: 0.26/1000 live births). The incidence in full-term babies declined from 0.30 (period 1) to 0.14/1000 live births (period 2, P = 0.04). Recto-vaginal screening cultures in full-term mothers increased significantly from 10/45 (period 1) to 10/14 (period 2, P = 0.002). EOGBS was diagnosed earlier in ARNs than in not-at-risk newborns (mean age 5.5 versus 14.5 hours, P = 0.007). There were no differences in age at diagnosis irrespective of whether ARNs were managed with laboratory testing plus observation (mean 3.5 hours, period 1) or with expectant observation alone (mean 2.4 hours, period 2). Conclusions: When screening cultures were handled according to standard protocols, cases of EOGBS in full-term newborns simultaneously decreased. ARNs were diagnosed in a timely manner through both strategies. The clinical yield of laboratory testing was negligible.

Kernicterus Associated with Hereditary Spherocytosis and UGT1A1 Promoter Polymorphism

Introduction: An apparent re-emergence of kernicterus has been recently reported, with some cases occurring in otherwise healthy breastfed newborn. Methods: We describe a case of kernicterus in a term Caucasian newborn. Results: An exceptional polymorphism of UGT1A1 gene promoter co-existed with asymptomatic inherited spherocytosis, due to erythroid anion exchange (band-3) deficiency. Both concurred to the development of severe neonatal hyperbilirubinaemia. Conclusion: As some cases of kernikterus remain unresolved, haemolytic diseases and bilirubin metabolism disorders should be carefully investigated in unexplained severe neonatal hyperbilirubinaemia.

Neutralization of a unique, negatively-charged residue in the voltage sensor of K V 7.2 subunits in a sporadic case of benign familial neonatal seizures

Benign Familial Neonatal Seizures (BFNS) is a rare, autosomal-dominant epilepsy of the newborn caused by mutations in K(v)7.2 (KCNQ2) or K(v)7.3 (KCNQ3) genes encoding for neuronal potassium (K(+)) channel subunits. In this study, we describe a sporadic case of BFNS; the affected child carried heterozygous missense mutations in both K(v)7.2 (D212G) and K(v)7.3 (P574S) alleles. Electrophysiological experiments revealed that the K(v)7.2 D212G substitution, neutralizing a unique negatively-charged residue in the voltage sensor of K(v)7.2 subunits, altered channel gating, leading to a marked destabilization of the open state, a result consistent with structural analysis of the K(v)7.2 subunit, suggesting a possible pathogenetic role for BFNS of this K(v)7.2 mutation. By contrast, no significant functional changes appeared to be prompted by the K(v)7.3 P574S substitution. Computational modelling experiments in CA1 pyramidal cells revealed that the gating changes introduced by the K(v)7.2 D212G increased cell firing frequency, thereby triggering the neuronal hyperexcitability which underlies the observed neonatal epileptic condition.

Factors associated with intrapartum transmission of group B Streptococcus.

Background: Data regarding the minimum duration of intrapartum antibiotic prophylaxis (IAP) required for preventing group B Streptococcus (GBS) early-onset sepsis are conflicting. Understanding factors that influence neonatal colonization (NC) might help us understand factors associated with failure of prophylaxis. Methods: This is a 14-month prospective cohort study conducted at a single tertiary care center with a screening-based strategy. Women were enrolled if they had ≥35 weeks’ gestation and were GBS-positive at the vaginal site on admission. Their neonates were cultured from the throat and rectum at 24–48 h after birth. Colony growth was graded semiquantitatively (from 1+ to 4+). Uni- and multivariate logistic regression analyses were performed to evaluate risk factors for NC. Results: There were 502 neonates, 458 of whom were exposed to IAP. All cases of NC were associated with a lack of IAP exposure (P<0.01), intrapartum fever ≥37.5°C (P<0.01) and African ethnicity (P<0.01). In the 458 IAP-exposed neonates, the rates of NC were low and did not vary significantly in the range of less than 1–12 h before delivery (score test for trend of odds, P = 0.13). The only independent factors associated with NC were intrapartum fever ≥37.5°C and heavy maternal colonization (P<0.01 and P=0.03, respectively). Conclusions: Heavy maternal colonization, intrapartum fever, African ethnicity and lack of IAP exposure were associated with GBS transmission in neonates born to women who were tested positive on admission. Low rates of NC were found among IAP-exposed neonates irrespective of IAP duration.

Neonatal herpes simplex virus

Herpes simplex virus is an important cause of neonatal infection, which can lead to death or long-term disabilities. Rarely in utero, the transmission frequently occurs during delivery. The disease may be disseminated, localized to the central nervous system, or involving skin, eye and/or mouth. Mortality rates markedly decreased with high-dose antiviral treatment. Diagnosis of neonatal infection is based on viral isolation from ulcerated vesicles or by scarifying mucocutaneous lesions. Recently polymerase chain reaction plays a central role for both viral detection (skin, mucosal, cerebrospinal fluid samples) and response to therapy. Vertical transmission may be decreased by prophylactic antiviral treatment.

Pure segmental trisomy 1q42-qter in a boy with a severe phenotype†

Since the early 1970s [Van den Berghe et al., 1973], several communications have described a distinct phenotype for the partial trisomy of the long arm of chromosome 1 and, after more than 100 cases reported so far, three hotspot breakpoints have been localized in the 1 long arm: q25 (only interstitial duplications have been described) [Schinzel, 1979], q32 [Duba et al., 1997], and q42 [Chia et al., 1988]. After delineating the common clinical features of a trisomy 1q phenotype, a tentative genotype/phenotype correlation has been made by grouping the signs according to the length of the duplicated segment: mental retardation, cranial abnormalities, hypertelorism, highly arched palate, malformation of the ears and of the toes have been foundpresent in all the cases, regardless of the length of the trisomic segment. Due to this fact, those manifestations have been assigned to the baseline phenotype of trisomy 1q syndrome, and have been attributed to the common and moredistal region, i.e., the 1q42->qter [Barros-Nunez et al., 1989]; moreover, various malformations (ocular, cardiac, urinary, gastrointestinal) have been observed to be superimposed on the common phenotype with an increased frequency in those cases with a larger trisomic imbalance [Gfatter et al., 1998]. Nevertheless, despite the number of studies published, a specific genotype/phenotype correlation for each duplicated segment has not been convincingly confirmed, due to the interference on the phenotype of concurring monosomies, resulting from an unbalanced segregation of parental balanced translocations [Schinzel, 1981]. In the present report, we characterize the clinical and molecular findings of a patient with pure de novo duplication of a 22.3 Mb segment and, by reviewing the literature, we discuss the genotype/ phenotype correlations of the pure distal trisomy 1q syndrome. The propositus is the fourth child of healthy consanguineous parents (3rd degree cousins). Parental ages at conception were 36 years for the mother and 39 years for the father. Three older sibs were healthy, and no previous miscarriages were reported. Family history was negative for mental retardation or congenital malformations. Pregnancy was uncomplicated until 30 weeks of gestation when an emergency caesarean was performed due to the placenta abruption. A boy was born with a birth weight of 1,205 g (25th centile), length of 41 cm (75th centile), and head circumference 30.5 cm (90th centile). The boy presented with a relative macrocephaly with wide fontanelles; a cerebral sonogram showed lateral and third ventricle enlargement with widened subarachnoid spaces. At birth, the following dysmorphic features were apparent: triangular face, wide anterior fontanelle, prominent forehead, low-set and abnormal ears, thick and arched eyebrows, ptosis, downslanting palpebral fissures, flat nasal bridge, long philtrum, downturned corners of the mouth, micrognathia (Fig. 1). Moreover, the child had right cryptorchidism, cutaneous bilateral 2nd and 3rd right toes syndactyly, and overlap of the 2nd and 3rd left toes. Ocular abnormalities were