Treatment of Mycoplasma hominis meningitis in infants is limited by a lack of consensus regarding therapy and limited pharmacokinetic data for agents to which M. hominis is susceptible. We report the successful treatment of a premature infant with M. hominis meningitis with doxycycline and moxifloxacin and provide a pharmacokinetic profile of moxifloxacin.

Patent ductus arteriosus (PDA) is a common diagnosis among extremely premature infants, especially in those with lung disease. Treatments are often used to close the PDA. Despite nearly three decades of research, the question of whether the benefits of treatments to prevent ductal patency or promote closure outweigh the risks of these treatments remains unanswered. The authors rarely use treatments designed to close the PDA. This article reviews three considerations in support of this restrained approach: rates of spontaneous closure of the ductus arteriosus; adverse effect of persistent ductal patency; and benefits and risks of treatments for closure.

Until approximately 15 years ago, sponsors rarely included children in the development of therapeutics. US and European legislation has resulted in an increase in the number of pediatric trials and specific label changes and dosing recommendations, although infants remain an understudied group. The lack of clinical trials in children is partly due to specific challenges in conducting trials in this patient population. Therapeutics in special populations, including premature infants, obese children and children receiving extracorporeal life support, are even less studied. National research networks in Europe and the USA are beginning to address some of the gaps in pediatric therapeutics using novel clinical trial designs. Recent innovations in pediatric clinical trial design, including sparse and scavenged sampling, population pharmacokinetic analyses and ‘opportunistic’ studies, have addressed some of the historical challenges associated with clinical trials in children.

Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.

Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.

Methods: We assessed infants of 23–30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000–2004.

Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and FiO2, and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org.

Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.

Objectives

To evaluate, in extremely low gestational age newborns (ELGANs), relationships between indicators of early postnatal hypotension and cranial ultrasound indicators of cerebral white matter damage imaged in the nursery and cerebral palsy diagnoses at 24 month follow-up.

Methods

The 1041 infants in this prospective study were born at < 28 weeks gestation, were assessed for 3 indicators of hypotension in the first 24 postnatal hours, had at least one set of protocol cranial ultrasound scans, and were evaluated with a structured neurologic exam at 24 months corrected age. Indicators of hypotension included: 1) lowest mean arterial pressure (MAP) in the lowest quartile for gestational age; 2) treatment with a vasopressor; and 3) blood pressure lability, defined as the upper quartile of the difference between each infant’s lowest and highest MAP. Outcomes included indicators of cerebral white matter damage, i.e. moderate/severe ventriculomegaly or an echolucent lesion on cranial ultrasound, and cerebral palsy diagnoses at 24 months gestation. Logistic regression was used to evaluate relationships among hypotension indicators and outcomes, adjusting for potential confounders.

Results

Twenty-one percent of surviving infants had a lowest blood pressure in the lowest quartile for gestational age, 24% were treated with vasopressors, and 24% had labile blood pressure. Among infants with these hypotension indicators, 10% percent developed ventriculomegaly and 7% developed an echolucent lesion. At 24-months follow-up, 6% had developed quadriparesis, 4% diparesis, and 2% hemiparesis. After adjusting for confounders, we found no association between indicators of hypotension, and indicators of cerebral white matter damage or a cerebral palsy diagnosis.

Conclusions

The absence of an association between indicators of hypotension and cerebral white matter damage and or cerebral palsy suggests that early hypotension may not be important in the pathogenesis of brain injury in ELGANs.

Background

To develop an accurate, proxy-reported bedside measurement tool for assessment of the severity of bronchopulmonary dysplasia (also called chronic lung disease) in preterm infants to supplement providers' current biometric measurements of the disease.

Methods

We adapted Patient-Reported Outcomes Measurement Information System (PROMIS) methodology to develop the Proxy-Reported Pulmonary Outcomes Scale (PRPOS). A multidisciplinary group of registered nurses, nurse practitioners, neonatologists, developmental specialists, and feeding specialists at five academic medical centers participated in the PRPOS development, which included five phases: (1) identification of domains, items, and responses; (2) item classification and selection using a modified Delphi process; (3) focus group exploration of items and response options; (4) cognitive interviews on a preliminary scale; and (5) final revision before field testing.

Results

Each phase of the process helped us to identify, classify, review, and revise possible domains, questions, and response options. The final items for field testing include 26 questions or observations that a nurse assesses before, during, and after routine care time and feeding.

Conclusions

We successfully created a prototype scale using modified PROMIS methodology. This process can serve as a model for the development of proxy-reported outcomes scales in other pediatric populations.

Considerable effort has been devoted to the development of strategies to reduce the incidence of chronic lung disease, including use of medications, nutritional therapies, and respiratory care practices. Unfortunately, most of these strategies have not been successful. To date, the only two treatments developed specifically to prevent CLD whose efficacy is supported by evidence from randomized, controlled trials are the parenteral administration of vitamin A and corticosteroids. Two other therapies, the use of caffeine for the treatment of apnea of prematurity and aggressive phototherapy for the treatment of hyperbilirubinemia were evaluated for the improvement of other outcomes and found to reduce CLD. Cohort studies suggest that the use of CPAP as a strategy for avoiding mechanical ventilation might also be beneficial. Other therapies reduce lung injury in animal models but do not appear to reduce CLD in humans. The benefits of the efficacious therapies have been modest, with an absolute risk reduction in the 7–11% range. Further preventive strategies are needed to reduce the burden of this disease. However, each will need to be tested in randomized, controlled trials, and the expectations of new therapies should be modest reductions of the incidence of the disease.