Dominique Astruc

Incidence and distribution of pathogens in early-onset neonatal sepsis in the era of antenatal antibiotics.

In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n= 36), amoxicillin resistance (n= 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance.

A Multicenter, Randomized, Placebo-Controlled Trial of Prophylactic Recombinant Granulocyte-Colony Stimulating Factor in Preterm Neonates with Neutropenia

OBJECTIVE To test the hypothesis that prophylactic treatment of neutropenic premature neonates with recombinant granulocyte-colony stimulating factor (rG-CSF) would reduce the incidence of nosocomial infections (NIs). STUDY DESIGN A total of 25 neonatal intensive care units participated in this multicenter, randomized, double-blind, placebo-controlled trial. Premature infants of gestational age (GA) <or= 32 weeks were included if they had a peripheral blood count showing < 1500 neutrophils/mm(3) for at least 24 hours during the first 3 weeks of life. A total of 200 infants received either rG-CSF (10 microg/kg/day) or placebo for 3 days. Primary outcome was survival free of infection for 4 weeks after treatment, assessed in an intention-to-treat analysis. RESULTS A total of 102 infants received rG-CSF (mean GA, 29.2 weeks), and 98 received placebo (mean GA, 29.1 weeks). Survival free of confirmed infection for 4 weeks after treatment was 74/102 in the rG-CSF group and 66/98 in the placebo group (P = .42). However, during 2 weeks, there was a significant difference between groups (86/102 vs 70/98; P = .028). CONCLUSIONS In this population, prophylactic rG-CSF did not significantly increase survival free of infection at 4 weeks after treatment. The transient effect observed at 2 weeks in the most immature infants should be evaluated further.

Moderate acoustic changes can disrupt the sleep of very preterm infants in their incubators

To evaluate the impact of moderate noise on the sleep of very early preterm infants (VPI).

Late-onset neonatal infections: incidences and pathogens in the era of antenatal antibiotics

Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of early-onset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p = 0.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p = 0.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. Conclusion Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure.

Diagnostic approach to neonatal hypotonia: retrospective study on 144 neonates.

The objectives of our study were to determine the actual frequency of the different disorders causing neonatal hypotonia and to assess the reliability of the first physical examination as well as the contribution of the main standard diagnostic tests. One hundred and forty-four infants diagnosed with neonatal hypotonia between January 1st 1999 and June 30th 2005 in our tertiary care facility were retrospectively included in the study. Perinatal history, clinical type of hypotonia, results of standard diagnostic tests, final diagnosis and outcome were abstracted from the original charts. A final diagnosis was reached in 120 cases. Central (cerebral) causes represented 82% of the elucidated cases, mostly hypoxic and hemorrhagic lesions of the brain (34%), chromosomal aberrations and syndromic disorders (26%) and brain malformations (12%). Peripheral (neuromuscular) causes were mainly represented by spinal muscular atrophy (6%) and myotonic dystrophy (4%). Positive predictive value of the initial clinical examination was higher in central type hypotonia. Neuroimaging, karyotype analysis and DNA-based tests were the most helpful diagnostic tools. These recent clinical data can be used to improve our strategy in investigating neonatal hypotonia and a diagnostic algorithm is proposed based on our findings.

Infants born very preterm react to variations of the acoustic environment in their incubator from a minimum signal-to-noise ratio threshold of 5 to 10 dBA

Introduction:Very early preterm infants (VPIs) are exposed to unpredictable noise in neonatal intensive care units. Their ability to perceive moderate acoustic environmental changes has not been fully investigated.Results:Physiological values of the 598 isolated sound peaks (SPs) that were 5–10 and 10–15 dB slow-response A (dBA) above background noise levels and that occured during infants’ sleep varied significantly, indicating that VPIs detect them. Exposure to 10–15 dBA SPs during active sleep significantly increased mean heart rate and decreased mean respiratory rate and mean systemic and cerebral oxygen saturations relative to baseline.Discussion:VPIs are sensitive to changes in their nosocomial acoustic environment, with a minimal signal-to-noise ratio (SNR) threshold of 5–10 dBA. These acoustic changes can alter their well-being.Methods:In this observational study, we evaluated their differential auditory sensitivity to sound-pressure level (SPL) increments below 70–75 dBA equivalent continuous level in their incubators. Environmental (SPL and audio recording), physiological, cerebral, and behavioral data were prospectively collected over 10 h in 26 VPIs (GA 28 (26–31) wk). SPs emerging from background noise levels were identified and newborns’ arousal states at the time of SPs were determined. Changes in parameters were compared over 5-s periods between baseline and the 40 s following the SPs depending on their SNR thresholds above background noise.

Exploring the olfactory environment of premature newborns: a French survey of health care and cleaning products used in neonatal units.

Aim:  To assess the main determinants of the newborn’s nosocomial olfactory environment.

Safety and effectiveness of skin-to-skin contact in the NICU to support neurodevelopment in vulnerable preterm infants.

Skin-to-skin contact (SSC) is a cornerstone of neurodevelopmentally supportive and family-oriented care for very low-birth-weight preterm infants (VPIs). However, performing SSC with unstable and/or ventilated VPIs remains challenging for caregiving teams and/or controversial in the literature. We first aimed to assess the safety and effectiveness of SSC with vulnerable VPIs in a neonatal intensive care unit over 12 months. Our second aim was to evaluate the impact of the respiratory support (intubation or not) and of the infants weight (above or below 1000 g) on the effects of SSC. Vital signs, body temperature, and oxygen requirement data were prospectively recorded by each infants nurse before (baseline), during (3 time points), and after their first or first 2 SSC episodes. We compared the variations of each parameter from baseline (analysis of variance for repeated measures with post hoc analysis when appropriate). We studied 141 SSCs in 96 VPIs of 28 (24-33) weeks’ gestational age, at 12 (0-55) days of postnatal age, and at a postmenstrual age of 30.5 (±1.5) weeks. During SSC, there were statistically significant increases in oxygen saturation (Sao2) (P < .001) with decreases in oxygen requirement (P = .043), a decrease in heart rate toward stability (P < .01) but a transient and moderate decrease in mean axillary temperature following the transfer from bed to mother (P < .05). Apneas/bradycardias requiring minor intervention occurred in 19 (13%) SSCs, without need for SSC termination. These variations were similar for intubated newborns (18%) as compared with newborns on nasal continuous positive airway pressure (52%) or breathing room air (30%). However, ventilated infants exhibited a significant increase in transcutaneous partial pressure of carbon dioxide (TcPco2) (P = .01), although remaining in a clinically acceptable range, and a greater decrease in oxygen requirements during SSC (P < .001) than nonventilated infants. Skin-to-skin contact in the neonatal intensive care unit seems safe and effective even in ventilated VPIs. Recording physiologic data of infants before, during, and after SCC provides data needed to secure changes of practice in SCC.

Congenital hyperekplexia: five sporadic cases

We report fives sporadic cases of hyperekplexia or startle disease characterized by a highly exaggerated startle reflex and tonic attacks. Affected neonates suffer from prolonged periods of stiffness and are at risk for sudden death from apnea. An early diagnosis is needed. Sudden loud sounds, unexpected tactile stimuli or percussion at the base of the nose can also elicit excessive jerking or tonic attack. The diagnosis of hyperekplexia is a purely clinical one. A defect of the alpha1 subunit of inhibitory glycine receptor (GLRA1) has been observed in the dominant form with a mutation in the chromosome 5. Clonazepam is effective and decreases the severity of the symptoms. The disease tends to improve after infancy and the psychomotor development is normal. The major form of “hyperekplexia” should be considered whenever one is confronted with neonatal hypertonicity associated with paroxysmal tonic manifestations (without electroencephalography anomalies). Conclusion: the diagnosis of hyperekplexia should be evaluated in any neonate with tonic attacks without evident cause.

Very preterm infants can detect small variations in light levels in incubators.

This prospective observational study was designed to improve our understanding of the responses of very preterm infants to light level variations in incubators and to evaluate what determined those reactions.