Uninformed Origins: Should We Be Advising Parents on the Source of Medicines and Therapies?

Respecting patient autonomy through the process of soliciting informed consent is a cornerstone of clinical ethics. In pediatrics, until a child becomes an adult or legally emancipated, that ethical tenet takes the form of respect for parental decision-making authority. In instances of respecting religious beliefs, doing so is not always apparent and sometimes the challenge lies not only in the healthcare provider's familiarity of religious restrictions but also their knowledge of medical interventions themselves which might conflict with those restrictions. We examine a case of a newborn receiving animal-derived surfactant, a common scenario in neonatology, and present considerations for providers to weigh when confronting when such an intervention might conflict with parent's religious beliefs. We end with strategizing ways to address this issue as a medical community.

Challenges in Prenatal Treatment with Dexamethasone.

Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency causes elevated androgen levels, which can lead to virilization of female external genitalia. Prenatal dexamethasone treatment has been shown to be effective in preventing virilization of external genitalia when started prior to 7-9 weeks of gestation in females with classic CAH. However, CAH cannot be diagnosed prenatally until the end of the first trimester. Treating pregnant women with a fetus at risk of developing classic CAH exposes a significant proportion of fetuses unnecessarily, because only 1 in 8 would benefit from treatment. Consequently, prenatal dexamethasone treatment has been met with much controversy due to the potential adverse outcomes when exposed to high-dose steroids in utero. Here, we review the short- and long-term outcomes for fetuses and pregnant women exposed to dexamethasone treatment, the ethical considerations that must be taken into account, and current practice recommendations.

Evidence-based, ethically justified counseling for fetal bilateral renal agenesis.

BACKGROUND: Not much data are available on the natural history of bilateral renal agenesis, as the medical community does not typically offer aggressive obstetric or neonatal care asbilateral renal agenesis has been accepted as a lethal condition. AIM: To provide an evidence-based, ethically justified approach to counseling pregnant women about the obstetric management of bilateral renal agenesis. STUDY DESIGN: A systematic literature search was performed using multiple databases. We deploy an ethical analysis of the results of the literature search on the basis of the professional responsibility model of obstetric ethics. RESULTS: Eighteen articles met the inclusion criteria for review. With the exception of a single case study using serial amnioinfusion, there has been no other case of survival following dialysis and transplantation documented. Liveborn babies die during the neonatal period. Counseling pregnant women about management of pregnancies complicated by bilateral renal agenesis should be guided by beneficence-based judgment informed by evidence about outcomes. CONCLUSIONS: Based on the ethical analysis of the results from this review, without experimental obstetric intervention, neonatal mortality rates will continue to be 100%. Serial amnioinfusion therefore should not be offered as treatment, but only as approved innovation or research.

The history of ethical decision making in neonatal intensive care.

Neonatal ethics has focused on 2 questions: is withholding potentially live-saving treatment from neonates ethically justified? and if so, who has the authority to decide? This article details how these questions developed and provides a description of the possible answers. In the first section, we review a selection of seminal articles by noted authors in the fields of ethics, medicine, and law. The second section provides a detailed account of the development of the Baby Doe Regulations and the impact they had on neonatal ethics, with particular attention to the emergence of the Best Interest Standard as a guideline for decision making. In the last section, we review the landmark position statements by the American Academy of Pediatric (AAP), and the focus on evidence-based decision making. We conclude that forgoing life-saving treatment is ethically justified. However, this requires a rigorous evidence-based process and is limited by the Best Interest Standard. The second question is more difficult to answer, but we feel that in light of legal limitations, physicians acting as both the infant advocate and a proxy for the state, decide what falls in the range of acceptable treatment options, with the parents free to choose within that range.

Treatment of methicillin-resistant Staphylococcus aureus in neonatal mice: lysostaphin versus vancomycin.

S. aureus is a significant cause of late-onset sepsis in neonates. Increasing antibiotic resistance, however, requires additional treatment options. Lysostaphin, an endopeptidase, has that potential. The objective of this study is to compare lysostaphin versus vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal mouse model. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against MRSA strain USA300 were determined using standard methods. To determine pharmacokinetics, neonatal pups received either vancomycin or lysostaphin intraperitoneal and serum samples were obtained. To evaluate efficacy, pups were infected s.c. and littermates randomized to receive either saline, vancomycin, or lysostaphin intraperitoneal. Pups were observed for survival and growth. Quantitative blood cultures were obtained 24 h after infection. The MIC/MBC for vancomycin and lysostaphin were 0.71/1.19 microg/mL and <0.008/0.015 microg/mL, respectively. Mean lysostaphin concentrations ranged from 2.34 to 8.92 microg/mL. Mean vancomycin concentrations ranged from 1.72 to 11.2 microg/mL. Lysostaphin improved survival compared with placebo (p < 0.00001) and vancomycin (p < 0.03). There was no significant difference in growth among the groups. All treatment regimens resulted in less bacteremia compared with placebo (p < 0.0001). Lysostaphin appears to be more effective than vancomycin in treating MRSA in a neonatal model.

Antibiotic prophylaxis improves Ureaplasma-associated lung disease in suckling mice.

Ureaplasma infection is associated with increased lung disease in high-risk neonates. Our goal was to determine the impact of antibiotic prophylaxis on Ureaplasma and oxygen-induced lung disease in newborn mice. In animal model development and prophylaxis experiments, pups were randomly assigned to either 0.8 or 0.21 inspired oxygen concentration [fraction of inspired oxygen (FiO2)] from 1 to 14 d of age and either Ureaplasma or 10 B media daily from 1 to 3 d. All pups were observed for growth and survival. Surviving pups had culture and PCR evaluated for blood, bronchoalveolar lavage, and lung, and lung weights, pathology, morphometry, histology, and immunohistochemistry were determined. In prophylaxis experiments, erythromycin, azithromycin, or normal saline was given for the first 3 d, and minimum inhibitory concentration and pharmacokinetics were determined. In model development, 0.8 FiO2 and Ureaplasma infection survival and growth were significantly decreased and lung edema and inflammation were significantly increased. In prophylaxis experiments, we observed significantly improved survival and growth with azithromycin versus normal saline controls, whereas erythromycin was not significantly different from controls, and decreased inflammatory response with azithromycin versus normal saline and erythromycin. In a neonatal mouse model of Ureaplasma and oxygen-induced lung disease, appropriate antibiotic prophylaxis improves survival and morbidity and decreases lung inflammation.

An ethically-justifiable, practical approach to decision-making surrounding conjoined-twin separation.

Conjoined twins present unique ethical and palliative care challenges. We present an ethically-justifiable, practical approach to decision-making with regards to surgical separation. These decisions must account for the short- and long-term prognoses for each infant prior to, and after, separation. Other considerations include the benefits and burdens of separation and the family's values and goals. Caregivers should recognize that decisions surrounding separation may be unduly influenced by social biases. The palliative care team aids in developing goals of care to guide decision-making by promoting communication between the medical team and family. They play an important role in supporting families regardless of the planned course of treatment. This support may be social or spiritual in nature, and is promoted by the interdisciplinary structure of the team. Early involvement of palliative care services facilitates complex decision making and can aid in the transition from cure-oriented therapies to support if needed during and after the dying process.

Two-Year Neurodevelopmental Outcome of an Infant Born at 21 Weeks' 4 Days' Gestation.

Recent literature confirms that, at the lower limit of extrauterine survival, substantial intercenter variability exists in resuscitation practice. The reasons for this variability are unclear, but may be related to disagreement on how to apply the best interests standard to extremely premature infants. Currently, both obstetric and pediatric societies recommend against assessing for viability or attempting resuscitation before 22 weeks' gestation. In this context, we report the unimpaired 2-year outcome of a female infant resuscitated after delivery at 21 weeks' 4 days' gestation and 410 g birth weight. She may be the most premature known survivor to date. This infant had multiple risk factors for adverse outcome, including prolonged mechanical ventilation, bronchopulmonary dysplasia, and threshold retinopathy of prematurity. She achieved discharge from the hospital on low-flow oxygen at 39 weeks' 4 days' gestation and 2519 g. At 24 months' and 8 days' chronological age, she achieved cognitive, motor, and language Bayley III scores of 90, 89, and 88, equivalent to 105, 100, and 103 at 20 months 2 days corrected age. It is known that active intervention policies at 22 weeks' gestation improves the outcome for those infants and it may be reasonable to infer that these benefits would extend, if to a lesser degree, into the 21st week. Ultimately, such limited data exist at this gestational age that the time may have arrived for obstetrical centers to begin systematically reporting fetal outcomes in the 21st week.

Fluidity models in ancient Greece and current practices of sex assignment.

Disorders of sexual differentiation such as androgen insensitivity and gonadal dysgenesis can involve an intrinsic fluidity at different levels, from the anatomical and biological to the social (gender) that must be considered in the context of social constraints. Sex assignment models based on George Engel's biopsychosocial aspects model of biology accept fluidity of gender as a central concept and therefore help establish expectations within the uncertainty of sex assignment and anticipate potential changes. The biology underlying the fluidity inherent to these disorders should be presented to parents at diagnosis, an approach that the gender medicine field should embrace as good practice. Greek mythology provides many accepted archetypes of change, and the ancient Greek appreciation of metamorphosis can be used as context with these patients. Our goal is to inform expertise and optimal approaches, knowing that this fluidity may eventually necessitate sex reassignment. Physicians should provide sex assignment education based on different components of sexual differentiation, prepare parents for future hormone-triggered changes in their children, and establish a sex-assignment algorithm.

Coagulase-negative staphylococcal infections in the neonate and child: an update.

Coagulase-negative staphylococcus (CONS) infection is the most common bloodstream infection treated in neonatal and pediatric intensive care units and significantly impacts patient mortality and morbidity. Staphylococcus epidermidis is the most common CONS species isolated clinically and investigated for its pathogenicity and virulence. Difficulties exist in the differentiation of CONS infection from culture contamination in clinical specimens, as CONS is a common skin commensal. Most CONS isolates have the mecA gene and exhibit beta-lactam resistance. The glycopeptide antibiotics, such as vancomycin, are the mainstay in therapy, although resistance has been reported. Arbekacin, linezolid, and streptogramins are newer antibiotics being evaluated as alternatives to glycopeptides. Monoclonal and polyclonal antibodies have been developed against the cell-wall components of staphylococcus and may hold promise for immune prophylaxis and treatment of CONS infection.

A Structured End-of-Life Curriculum for Neonatal-Perinatal Postdoctoral Fellows.

Death in tertiary care neonatal intensive care units is a common occurrence. Despite recent advances in pediatric palliative education, evidence indicates that physicians are poorly prepared to care for dying infants and their families. Numerous organizations recommend increased training in palliative and end-of-life care for pediatric physicians. The purpose of this study is to develop a structured end-of-life curriculum for neonatal-perinatal postdoctoral fellows based on previously established principles and curricular guidelines on end-of-life care in the pediatric setting. Results demonstrate statistically significant curriculum effectiveness in increasing fellow knowledge regarding patient qualification for comfort care and withdrawal of support (P = .03). Although not statistically significant, results suggest the curriculum may have improved fellows' knowledge of appropriate end-of-life medical management, comfort with addressing the family, and patient pain assessment and control.