Early-onset Infection Research Articles

Gastroschisis and low incidence of early-onset infection: a case for antimicrobial stewardship.

Early onset infection (EOI) in gastroschisis is rare. Excess antibiotic exposure in neonates increases necrotizing enterocolitis and mortality. We evaluated antibiotic exposure and EOI in gastroschisis. Retrospective cohort analysis between 2010-2016 in the Children's Hospital Neonatal Database. Included: Infants ≥32 weeks with gastroschisis admitted <48 h. Excluded: major anomalies or surgical intervention prior to admission. EOI diagnosis (<72 h). In 2021 patients with gastroschisis, median gestational age was 36 weeks (IQR 35, 37). 93.9% patients received empiric antibiotics after delivery, with median 7 days duration (IQR 3, 9). Only 13 patients (0.64%) had early positive blood culture. The rate of late onset blood stream infection (7.08%) was higher, and higher in complex (18%) than simple gastroschisis (4.8%, p < 0.001). Despite low incidence of EOI and risks of excess antibiotic exposure, neonates with gastroschisis are exposed to long courses of empiric antibiotics. These data should stimulate interinstitution work to improve antibiotic prescribing.

Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.

Group B streptococcus — a pathogen not restricted to neonates

ObjectivesThis was a retropective study of invasive group B streptococcal (GBS) infections isolated from blood, cerebrospinal fluid (CSF), synovial fluid, peritoneal fluid, pleural fluid, pericardial fluid and corpus vitreum in a defined region in southwest Sweden over a 14-year period. DesignInformation on all invasive GBS infections was obtained from all four bacteriological laboratories in the region, with data obtained from individual patient records. ResultsGBS was isolated from normally sterile body fluids in 1244 samples (579 from females and 665 from males) from 1101 patients. Of these patients, 196 were neonates. The incidence in neonates (0–27 days) was 7.3 per 100 000 live births per year, but there was a significant decrease from 2012 when risk-factor-based intrapartum antibibiotic prophylaxis was implemented. The great majority of neonatal infections were very early-onset infections. The incidence rates in children (28 days to 17 years), adults (18–64 years) and elderly patients (≥ 65 years) were 1.3, 3.6, and 12.9 per 100 000 per year, respectively. The majority of children and adults had severe underlying diseases, but severe infections were also seen in individuals with no risk factors. ConclusionsGBS is an important pathogen in all age groups. Intrapartum antibiotic prophylaxis significantly decreases very early-onset infections.

Somatic hypermutation defects in two adult hyper immunoglobulin M patients

Hyper immunoglobulin M (HIGM) syndrome is a rare disorder of the immune system with impaired antibody functions. The clinical picture of the patients varies according to the underlying genetic variation. In this study, we identified two novel variants in AID and UNG genes, which are associated with autosomal recessive type HIGM, by targeted next-generation sequencing (NGS) panel. A biallelic 11 base pair deletion (c.278_288delATGTGGCCGAC) in the coding sequence of activation-induced cytidine deaminase (AID) gene was identified in a 36-year-old patient. Biallelic two base pair insertion in exon 7 of uracil nucleoside glycosylase (UNG) gene (c.924_925insGG) was identified in a 40-year-old patient. Both variants were confirmed by Sanger sequencing. HIGM, like many of the other primary immunodeficiencies, is a rare and difficult-to-diagnose entity with heterogeneous clinical phenotypes. It should be suspected in patients with a history of early-onset recurrent respiratory infections, enlarged lymph nodes, and autoimmune disorders. There might be a delay in diagnosis until adulthood especially in subtle cases or if HIGM is not included in the differential diagnosis due lacking of awareness. In this regard, genetic testing with NGS-based diagnostic panels provide a rapid and reasonable tool for the molecular diagnosis of patients with immunodeficiencies and hence, decrease the time to diagnose and prevent infection-related complications associated with increased morbidity and mortality.

Very early complications of neonatal asphyxia

Background: Neonatal asphyxia may develop complications and may lead to death. This study aimed to know the incidence of complications of neonatal asphyxia within 24 hours after birth. Methods: This cohort study was performed from June 2015 to May 2016. The inclusion criteria were gestational age &gt;28 weeks or birth weight &gt;1000 grams and need positive pressure ventilation (with or without intubation) for 30 seconds or more. Neonates with major congenital anomalies and early-onset infection were excluded from the study. Subjects were followed up for 24 hours to identify any complications related to neonatal asphyxia. Further follow-up was done until the subject was discharged home or died during hospitalization. Complications of neonatal asphyxia monitored were central nervous system, cardiovascular system, respiratory system, gastrointestinal tract system, urinary tract system, hematology system, metabolic disorder, and electrolyte imbalance. An attending neonatologist or neonatology trainee performed a clinical assessment of complications, and a trained medical doctor did the data collection. We analyzed the incidence of neonatal asphyxia complication, mortality, and gestational age sub-analysis. A student t-test with a 95% significance level was used to analyze dichotomous data and regression analysis for correlation between the level of resuscitation and the number of complications. Results: There were 94 subjects included in the study. There was no significant difference in complications in sex, birth weight, gestational age, 1 and 5-minute Apgar score, and level of resuscitation. Seventeen (18.1%) of subjects had no complications. The incidence of complications was respiratory system 67%, hypoglycemia 37.2%, electrolyte imbalance 8.5%, CNS 6.4%, CVS and hematology system complications were 2.1%, and GIT 1.1%. Subjects with 1 organ complication were 48.9%, 2 complications, 3 complications and 4 complications were 24.5%, 7.4%, and 1.1% respectively. Lower gestational age had more complications (p: 0.025). There was weak correlation between level of resuscitation and number of complication (r2: 0.017, p: 0.22), for term (r2: 0.31; p: 0.27), preterm (r2: 0.31; p: 0.27), and very preterm (r2: 0.00; p: 0.98). Three out of five death cases occurred within first week. Conclusion: The most common neonatal asphyxia complication was respiratory distress which may lead to early neonatal death.

Corrigendum to "Assessment of risk factors for early-onset deep surgical site infection following primary total hip arthroplasty for osteoarthritis" published in J. Bone Joint Infect., 6, 443-450, 2021.

Corrigendum to "Assessment of risk factors for early-onset deep surgical site infection following primary total hip arthroplasty for osteoarthritis" published in J. Bone Joint Infect., 6, 443-450, 2021.

Early life inflammation is associated with spinal cord excitability and nociceptive sensitivity in human infants

Immune function and sensitivity to pain are closely related, but the association between early life inflammation and sensory nervous system development is poorly understood—especially in humans. Here, in term-born infants, we measure brain activity and reflex withdrawal activity (using EEG and EMG) and behavioural and physiological activity (using the PIPP-R score) to assess the impact of suspected early-onset neonatal infection on tactile- and noxious-evoked responses. We present evidence that neonatal inflammation (assessed by measuring C-reactive protein levels) is associated with increased spinal cord excitability and evoked brain activity following both tactile and noxious stimulation. There are early indications that this hyperalgesia could be maintained post-inflammation, supporting pre-clinical reports of early-life immune dysfunction influencing pain sensitivity in adults.

BCL10 loss-of-function novel mutation leading to atypical severe combined immunodeficiency

BackgroundSevere combined immunodeficiency (SCID) is characterized by severe, early-onset infection in infants. B-cell lymphoma/leukemia (BCL) 10 defects causing SCID have been reported previously in two patients. Material & methodsA seven-month-old female infant was admitted with bilateral pneumonia requiring ventilatory support. She had a history of recurrent infections starting from four months of age. The patient was investigated for primary immunodeficiency. ResultsImmunological investigations revealed hypogammaglobulinemia with normal CD4 and CD8 lymphocyte counts, while a lymphocyte proliferation assay showed absent response to phytohemagglutinin stimulation, thereby establishing the diagnosis of an atypical form of SCID. Genetic testing revealed a homozygous mutation in the BCL10 gene, with both parents demonstrating a heterozygous state (NM_003921.5:c.271A > C:p.[Thr91Pro]). The patient died before bone marrow transplantation due to severe disseminated adenovirus disease. ConclusionWe report the first patient from the Middle East with a novel homozygous mutation in the BCL10 gene causing SCID.

Obstetric Risk Factors and Serological Characteristics of Early-Onset Neonates Bacterial Infections.

PurposeTo analyze the obstetric high-risk factors and serological characteristics of early-onset neonatal bacterial infections (EONBI).Methods119 neonates with early-onset bacterial infection who were admitted to the neonatal ward of our hospital from October 2020 to December 2021 were recorded as the study group, and 100 neonates without bacterial infection who were admitted during the same period were used as the reference group. Comparative analysis of obstetric high-risk factors and serological characteristics of EONBI.ResultsThere was no statistical difference between the two groups in terms of gender and age at admission (P > 0.05). The gestational age and birth weight of newborns in the study group were lower than those in the reference group (P < 0.001). Comparing the maternal factors of EONBI between the two groups, there was no statistical difference in age, number of obstetric inspections, whether to use antibiotics, and mode of delivery (P > 0.05). Univariate analysis showed that preterm birth, unexplained asphyxia, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h were significantly associated with EONBI (P < 0.05); while there was no significant difference between the two groups in the comparison between diabetic mother and child and maternal fever at delivery (P > 0.05). Multifactorial analysis showed that preterm birth, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h had a good multivariate dependence on EONBI (P < 0.05), while there was no significant association with unexplained asphyxia, diabetic mother and child, and maternal fever at delivery (P > 0.05). The incidence of neonatal temperature >37.9°C was higher in the study group than in the reference group (P < 0.05), and there were no statistical differences in the comparison of other clinical manifestations (P > 0.05). The CRP level of neonates in the study group (47.33 ± 4.14) mg/L was higher than that of the reference group (4.84 ± 1.03) mg/L (P < 0.001). The WBC level of neonates in the study group (5.64 ± 1.18) 109/L was higher than that of the reference group (0.28 ± 0.04) 109/L (P < 0.001). The PCT level of neonates in the study group (5.41 ± 0.85) µg/L was higher than that of the reference group (0.24 ± 0.07) µg/L (P < 0.001).ConclusionEONBI is closely associated with several obstetric high-risk factors, including preterm birth, fecal contamination of amniotic fluid, maternal infection during pregnancy, and premature rupture of membranes ≥18 h; EONBI has no specific symptoms and signs, but serum CRP, WBC, and PCT levels are significantly higher than those of newborns without co-infection with bacteria.

Emerging Antibiotic Resistance Patterns in a Neonatal Intensive Care Unit in Pune, India: A 2-Year Retrospective Study.

Objective:Treating neonatal bloodstream infections and meningitis in South Asia remains difficult given high rates of antimicrobial resistance (AMR). To evaluate changing epidemiology of neonatal infections, we assessed pathogen-specific and clinical features of culture-proven infections in neonates admitted to a neonatal intensive care unit (NICU) in Pune, India.Materials and MethodsThis retrospective cohort study was performed in the King Edward Memorial Hospital and Research Center NICU over 2 years between January 1, 2017 and December 31, 2018. We included all neonates admitted to the NICU with positive blood or cerebrospinal fluid cultures. Demographic, clinical, and microbiologic data were collected from the medical record. We reviewed antimicrobial susceptibility testing (AST) of all isolates.ResultsThere were 93 culture-positive infections in 83 neonates, including 11 cases of meningitis. Fifteen (18%) neonates died. Gram-negative pathogens predominated (85%) and AST showed 74% resistance to aminoglycosides, 95% resistance to third/fourth generation cephalosporins, and 56% resistance to carbapenems. Resistance to colistin was present in 30% of Klebsiella pneumoniae isolates. Birth weight <1,000 g [odds ratio (OR) 6.0, p < 0.002], invasive respiratory support (OR 7.7, p = 0.001), and antibiotics at the time of culture (OR 4.2, p = 0.019) were associated with increased risk of mortality. Rates of AMR to all major antibiotic classes were similar between early onset and late onset infections. There was no association between carbapenem resistance and mortality.ConclusionIn our NICU in India, there are high rates of AMR among Gram-negative pathogens that are predominantly responsible for infections. Given higher colistin resistance in this cohort than previously reported, hospitals should consider routinely testing for colistin resistance.

Evaluation of Infection and Effective Factors in Impacted Mandibular Third Molar Surgeries: A Cross-Sectional Study.

Materials and Methods This cross-sectional study was performed on 148 patients. The incidence of infection was recorded one week, two weeks, and one month after surgery. Independent variables included age, gender, the presence of periapical radiolucent lesions measuring ≥3 mm, the caries of the adjacent second molar, education level of the surgeon, difficulty index, suture type, and flap type. The outcome variable was the incidence of infection. Results Among the study subjects, 37.2% were male and 62.8% were female. The mean age was 25.24 ± 4.31 years at the time of surgery. Although early onset infection occurred in 3.4% of patients, none of them developed a delayed-onset infection during the four weeks after surgery. Pederson difficulty index (OR = 3.81, P=0.03) and the education level of the surgeon (OR = 0.14, P=0.021) were associated with postop infection. Conclusions Based on the results of the current study, postop infection was rare. Furthermore, both the Pederson difficulty index and the education level of the surgeon could predict the risk of infection after impacted mandibular third molar surgeries.

Procalcitonin is associated with postnatal respiratory condition severity in preterm neonate.

Postnatal respiratory failure is common in preterm neonates and is difficult to distinguish from early-onset neonatal bacterial infection by clinical symptoms. Similar to C-reactive protein (CRP), procalcitonin (PCT) is used as a marker of bacterial infection. Recently, it has been reported that the serum PCT levels increase because of respiratory failure immediately after birth. However, there is insufficient information concerning the relationship between biological inflammation markers, such as PCT and CRP, and postnatal respiratory condition severity. Preterm neonates were classified according to the received respiratory management as follows: nonrespiratory support (NRS), respiratory support (RS), surfactant administration therapy (STA), and STA with nitric oxide inhalation therapy (NO). The median serum PCT and CRP levels at 12-36 h postnatally were compared among the four groups. Additionally, the median serum PCT and CRP levels in the STA group were compared by STA timing and STA number. The PCT levels for the NRS, RS, STA, and NO groups were 1.04, 6.46, 12.93, and 86.79 μg/L, respectively; the CRP levels were 0.40, 0.80, 1.10, and 16.40 mg/L, respectively. The PCT levels were significantly lower among neonates receiving STA in the birth subgroup (4.82 μg/L) than among those receiving STA in the admission subgroup (14.71 μg/L). The PCT levels were significantly higher among the STA multiple-dose subgroup (24.87 μg/L) than among the STA single-dose subgroup (12.47 μg/L). No significant differences in the CRP levels were observed. The serum PCT levels in preterm neonates were associated with postnatal respiratory condition severity.

Study protocol for a population-based observational surveillance study of culture-confirmed neonatal bloodstream infections and meningitis in South Africa: Baby GERMS-SA

IntroductionWorldwide, neonatal mortality remains high accounting for 47% of childhood deaths in 2019 and including an estimated 500 000 deaths from neonatal infections. While 42% of global neonatal deaths occur...

Outcomes of Infants Born to Group B Streptococcus-Positive Mothers with a Reported Penicillin Allergy

Group B Streptococcus (GBS) is the leading cause of early-onset sepsis in infants in the United States. Penicillin or ampicillin are first-line prophylactic antibiotics given to GBS-colonized mothers to prevent early-onset neonatal sepsis. Cefazolin, clindamycin, or vancomycin are used for women who report a penicillin allergy. We hypothesize that reported penicillin allergy in GBS-positive mothers is associated with an increased risk of early-onset GBS infection and longer duration of hospitalization for infants with increased interventions.

A rapid intrapartum test for group B Streptococcus to reduce antibiotic usage in mothers with risk factors: the GBS2 cluster RCT.

Mother-to-baby transmission of group B Streptococcus (Streptococcus agalactiae) is the main cause of early-onset infection. We investigated if intrapartum antibiotic prophylaxis directed by a rapid intrapartum test reduces maternal and neonatal antibiotic use, compared with usual care (i.e. risk factor-directed antibiotics), among women with risk factors for vertical group B Streptococcus transmission, and examined the accuracy and cost-effectiveness of the rapid test. An unblinded cluster randomised controlled trial with a nested test accuracy study, an economic evaluation and a microbiology substudy. UK maternity units were randomised to either a strategy of rapid test or usual care. Vaginal and rectal swabs were taken from women with risk factors for vertical group B Streptococcus transmission in established term labour. The accuracy of the GeneXpert® Dx IV GBS rapid testing system (Cepheid, Maurens-Scopont, France) was compared with the standard of selective enrichment culture in diagnosing maternal group B Streptococcus colonisation. Primary outcomes were rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection and accuracy estimates of the rapid test. Secondary outcomes were maternal antibiotics for any indication, neonatal antibiotic exposure, maternal antibiotic duration, neonatal group B Streptococcus colonisation, maternal and neonatal antibiotic resistance, neonatal morbidity and mortality, and cost-effectiveness of the strategies. Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units and 906 mothers (951 babies) participated in usual-care units. There were no differences in the rates of intrapartum antibiotic prophylaxis for preventing early-onset group B Streptococcus infection in the rapid test units (41%, 297/716) compared with the usual-care units (36%, 328/906) (risk ratio 1.16, 95% confidence interval 0.83 to 1.64). There were no differences between the groups in intrapartum antibiotic administration for any indication (risk ratio 0.99, 95% confidence interval 0.81 to 1.21). Babies born in the rapid test units were 29% less likely to receive antibiotics (risk ratio 0.71, 95% confidence interval 0.54 to 0.95) than those born in usual-care units. The sensitivity and specificity of the rapid test were 86% (95% confidence interval 81% to 91%) and 89% (95% confidence interval 85% to 92%), respectively. In 14% of women (99/710), the rapid test was invalid or the machine failed to provide a result. In the economic analysis, the rapid test was shown to be both less effective and more costly and, therefore, dominated by usual care. Sensitivity analysis indicated potential lower costs for the rapid test strategy when neonatal costs were included. No serious adverse events were reported. The Group B Streptococcus 2 (GBS2) trial found no evidence that the rapid test reduces the rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection. The rapid test has the potential to reduce neonatal exposure to antibiotics, but economically is dominated by usual care. The accuracy of the test is within acceptable limits. The role of routine testing for prevention of neonatal infection requires evaluation in a randomised controlled trial. Current Controlled Trials ISRCTN74746075. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 12. See the NIHR Journals Library website for further project information.

Two-stage exchange for PJI with co-existing cerclages for fracture: higher rates of early re-infections and difficult to treat microbes

IntroductionPeriprosthetic joint infections (PJI) with osteosynthesis material for contemporaneous fractures are a challenging, yet poorly described condition. This study will analyze PJI with co-existing fractures treated with cerclages and two-stage exchange.Materials and methodsPatients with and without cerclages for coexisting periprosthetic fractures, undergoing two-stage exchange for PJI of hip or knee, between 06/2013 and 02/2016, were compared concerning baseline characteristics and re-infection rate in the course of a 2 year follow-up. All patients were treated with a standardized two-stage protocol. A PJI was defined according to the EBJIS criteria. All foreign material, including cerclages, was sent in for sonication for microbiological analysis.ResultsNinety-six patients treated with two-stage exchange for PJI could be included. Co-existing fractures treated with cerclage were identified in nine patients (9.3%, study group). Diaphyseal femoral simple in five cases (AO2A3) and proximal intertrochanteric in three cases (AO1A3) were the leading fracture locations. In one patient, cerclage implantation was performed prior to prosthesis explantation, in six, during prosthesis explantation, and in two, in the course of prosthesis reimplantation. The study group showed a significantly higher rate of difficult to treat microbes (44.4%; 8.0%; p = .001), Charlson Comorbidity Index (5.4; 3.7; p = .033), relapse infections with the same microbe (22.2%; 1.1%; p = .001), and early-onset infections (< 30 days) (11.1%; 1.1%; p = .046), than the comparison two-stage exchange group without fractures. In contrast, age (72.5 study group; 68.2 comparison group; p = .224), rate of revisions for PJI in the past (55.5%; 51.7%; p = .827), and total re-infection rate (22.2%; 10.3%; p = .287) did not show a difference.ConclusionPJI with co-existing cerclages for fractures were associated with multi-resistant microbes, relapse by the same microbe and early-onset re-infections. Cerclages might be considered a potential source of re-infection during a two-stage exchange. However, statistical weaknesses and a small study group must be considered limitations of the study.

Capnocytophaga Sepsis in a Preterm Neonate: A Case Report

Background Capnocytophaga is an anaerobic gram-negative bacillus part of oral flora in humans, cats, and dogs. It usually causes periodontal infection but may exhibit systemic manifestations, particularly in immunocompromised individuals. In rare cases, it may cause chorioamnionitis leading to preterm birth and early-onset neonatal sepsis. Case Presentation We present a rare case of early-onset sepsis due to Capnocytophaga in an extremely preterm newborn presenting severe respiratory distress, lethargy, and leukopenia at birth. This was treated with Cefotaxime for 14 days. Conclusion Our case report highlights the importance of considering unusual pathogens such as Capnocytophaga as a cause for intra-amniotic infections leading to preterm birth and early-onset neonatal infection.

Increased Colostral Concentration of Macrophage Migration Inhibitory Factor in Mothers with Premature Rupture of Membranes.

Objective: The colostrum contains macrophage migration inhibitory factor (MIF), which plays an important role in protecting newborns from infections. As such, colostrum may be specifically important to prevent early onset neonatal sepsis among neonates born after premature rupture of membranes (PROM). However, the effect of PROM on the colostral MIF concentration has not been previously described. The aim of this study is to compare the concentration of MIF in the colostrum of mothers with and without PROM. Methods: The study group consisted of 44 women, 22 of whom had PROM. Colostrum was expressed and collected within 72 hours of birth. MIF concentration was measured using the enzyme-linked immunosorbent assay method and compared between mothers with and without PROM. Results: There were no differences between the two groups (PROM group n = 22, control group n = 22) with regard to the age of mothers, mode of delivery, neonatal gestational age, birth weight, and sex of the infants (p > 0.05). The colostral MIF concentration was significantly higher among mothers with than without PROM (p = 0.0001). There was a positive and significant correlation between the colostral MIF concentration and PROM duration (r = 0.314, p = 0.038). Conclusions: PROM was associated with a higher colostral MIF concentration, with this concentration being positively correlated with the duration of PROM. This increased concentration may be important in offering these neonates additional protection against early onset infections, which is a risk associated with PROM.

Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018

Despite improvement during recent decades, extremely preterm infants continue to contribute disproportionately to neonatal mortality and childhood morbidity. To review survival, in-hospital morbidities, care practices, and neurodevelopmental and functional outcomes at 22-26 months' corrected age for extremely preterm infants. Prospective registry for extremely preterm infants born at 19 US academic centers that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. The study included 10 877 infants born at 22-28 weeks' gestational age between January 1, 2013, and December 31, 2018, including 2566 infants born before 27 weeks between January 1, 2013, and December 31, 2016, who completed follow-up assessments at 22-26 months' corrected age. The last assessment was completed on August 13, 2019. Outcomes were compared with a similar cohort of infants born in 2008-2012 adjusting for gestational age. Extremely preterm birth. Survival and 12 in-hospital morbidities were assessed, including necrotizing enterocolitis, infection, intracranial hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia. Infants were assessed at 22-26 months' corrected age for 12 health and functional outcomes, including neurodevelopment, cerebral palsy, vision, hearing, rehospitalizations, and need for assistive devices. The 10 877 infants were 49.0% female and 51.0% male; 78.3% (8495/10848) survived to discharge, an increase from 76.0% in 2008-2012 (adjusted difference, 2.0%; 95% CI, 1.0%-2.9%). Survival to discharge was 10.9% (60/549) for live-born infants at 22 weeks and 94.0% (2267/2412) at 28 weeks. Survival among actively treated infants was 30.0% (60/200) at 22 weeks and 55.8% (535/958) at 23 weeks. All in-hospital morbidities were more likely among infants born at earlier gestational ages. Overall, 8.9% (890/9956) of infants had necrotizing enterocolitis, 2.4% (238/9957) had early-onset infection, 19.9% (1911/9610) had late-onset infection, 14.3% (1386/9705) had severe intracranial hemorrhage, 12.8% (1099/8585) had severe retinopathy of prematurity, and 8.0% (666/8305) had severe bronchopulmonary dysplasia. Among 2930 surviving infants with gestational ages of 22-26 weeks eligible for follow-up, 2566 (87.6%) were examined. By 2-year follow-up, 8.4% (214/2555) of children had moderate to severe cerebral palsy, 1.5% (38/2555) had bilateral blindness, 2.5% (64/2527) required hearing aids or cochlear implants, 49.9% (1277/2561) had been rehospitalized, and 15.4% (393/2560) required mobility aids or other supportive devices. Among 2458 fully evaluated infants, 48.7% (1198/2458) had no or mild neurodevelopmental impairment at follow-up, 29.3% (709/2419) had moderate neurodevelopmental impairment, and 21.2% (512/2419) had severe neurodevelopmental impairment. Among extremely preterm infants born in 2013-2018 and treated at 19 US academic medical centers, 78.3% survived to discharge, a significantly higher rate than for infants born in 2008-2012. Among infants born at less than 27 weeks' gestational age, rehospitalization and neurodevelopmental impairment were common at 2 years of age.

Rapid intrapartum test for maternal group B streptococcal colonisation and its effect on antibiotic use in labouring women with risk factors for early-onset neonatal infection (GBS2): cluster randomised trial with nested test accuracy study

BackgroundMother-to-baby transmission of group B Streptococcus (GBS) is the main cause of early-onset infection. We evaluated whether, in women with clinical risk factors for early neonatal infection, the use of point-of-care rapid intrapartum test to detect maternal GBS colonisation reduces maternal antibiotic exposure compared with usual care, where antibiotics are administered due to those risk factors. We assessed the accuracy of the rapid test in diagnosing maternal GBS colonisation, against the reference standard of selective enrichment culture.MethodsWe undertook a parallel-group cluster randomised trial, with nested test accuracy study and microbiological sub-study. UK maternity units were randomised to a strategy of rapid test (GeneXpert GBS system, Cepheid) or usual care. Within units assigned to rapid testing, vaginal-rectal swabs were taken from women with risk factors for vertical GBS transmission in established term labour. The trial primary outcome was the proportion of women receiving intrapartum antibiotics to prevent neonatal early-onset GBS infection. The accuracy of the rapid test was compared against the standard of selective enrichment culture in diagnosing maternal GBS colonisation. Antibiotic resistance profiles were determined in paired maternal and infant samples.ResultsTwenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units; 906 mothers (951 babies) were in usual care units. There was no evidence of a difference in the rates of intrapartum antibiotic prophylaxis (relative risk 1.16, 95% CI 0.83 to 1.64) between the rapid test (41%, 297/716) and usual care (36%, 328/906) units. No serious adverse events were reported. The sensitivity and specificity measures of the rapid test were 86% (95% CI 81 to 91%) and 89% (95% CI 85 to 92%), respectively. Babies born to mothers who carried antibiotic-resistant Escherichia coli were more likely to be colonised with antibiotic-resistant strains than those born to mothers with antibiotic-susceptible E. coli.ConclusionThe use of intrapartum rapid test to diagnose maternal GBS colonisation did not reduce the rates of antibiotics administered for preventing neonatal early-onset GBS infection than usual care, although with considerable uncertainty. The accuracy of the rapid test is within acceptable limits.Trial registrationISRCTN74746075. Prospectively registered on 16 April 2015