John D. Lantos

Summary Proceedings From the Neonatal Pain-Control Group

Recent advances in neurobiology and clinical medicine have established that the fetus and newborn may experience acute, established, and chronic pain. They respond to such noxious stimuli by a series of complex biochemical, physiologic, and behavioral alterations. Studies have concluded that controlling pain experience is beneficial with respect to short-term and perhaps long-term outcomes. Yet, pain-control measures are adopted infrequently because of unresolved scientific issues and lack of appreciation for the need for control of pain and its long-term sequelae during the critical phases of neurologic maturation in the preterm and term newborn. The neonatal pain-control group, as part of the Newborn Drug Development Initiative (NDDI) Workshop I, addressed these concerns. The specific issues addressed were (1) management of pain associated with invasive procedures, (2) provision of sedation and analgesia during mechanical ventilation, and (3) mitigation of pain and stress responses during and after surgery in the newborn infant. The cross-cutting themes addressed within each category included (1) clinical-trial designs, (2) drug prioritization, (3) ethical constraints, (4) gaps in our knowledge, and (5) future research needs. This article provides a summary of the discussions and deliberations. Full-length articles on procedural pain, sedation and analgesia for ventilated infants, perioperative pain, and study designs for neonatal pain research were published in Clinical Therapeutics (June 2005).

Screening for Sudden Cardiac Death in the Young: Report From a National Heart, Lung, and Blood Institute Working Group

Sudden cardiac death (SCD) in the young (SCDY) has a devastating impact on families, care providers, and the community and attracts significant public and media attention. Sudden cardiac death is defined as an abrupt and unexpected death due to a cardiovascular cause, typically occurring 1 hour from the onset of symptoms. Depending on the source, “young” is variably defined as those less than 25, 30, 35, or 40 years of age. Estimates of the incidence of SCDY (not including infants) vary broadly from 0.6 to 6.2 per 100 000 persons. 1–3 Sudden infant death syndrome (SIDS) may be related to SCD in some infants. Sudden infant death syndrome is defined as the sudden death of an infant 1 year of age that cannot be explained after a thorough investigation is conducted, including an autopsy, death scene evaluation, and review of the clinical history. The incidence of SIDS ranges from 50 to 100 in 100 000,4 and emerging data suggest that as many as 10% to 15% of SIDS deaths are associated with functional cardiac ion channelopathy gene variants.5 The most common diagnoses that increase risk for SCDY include hypertrophic cardiomyopathy (HCM), coronary artery anomalies of wrong sinus origin, myocarditis, arrhythmogenic right ventricular cardiomyopathy, and ion channelopathies.6 The latter category includes hereditary diseases such as the congenital long-QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome, among other less common channelopathies. These diseases are typically undetected before the SCD event. Estimated prevalence rates of these conditions range from 1 per 500 persons for HCM to 1 per 2500 for the LQTS. SCD related to these diagnoses has been documented in infancy and during competitive athletics. In addition, prescription stimulant use for treatment of attention deficit hyperactivity disorder (ADHD) has been postulated to be a trigger for SCD.7,8 Sudden cardiac death in the young is a critical public health issue. A young life cut short represents a devastating event for families, and is associated with many lost productive years. There is significant dissonance among experts in the field about the best approach to prevent SCDY in the United States. Some experts support the implementation of largescale cardiovascular screening programs in infants, in athletes, or in all children to identify at-risk individuals in an effort to prevent SCDY. Cardiovascular screening for SCDY typically involves the addition of an ECG to the current standard of care of history and physical examination. Echocardiography and genetic testing represent alternative or additional screening modalities. Observational data from the Veneto region of Italy suggest that ECG screening can successfully identify at-risk cardiovascular diseases and dramatically reduce the incidence of SCD in competitive athletes.9,10 Proponents of ECG screening in the United States suggest that it can be effective, feasible, and cost-effective. 11 Critics of ECG screening cite a lack of evidence to support its effectiveness or feasibility in the United States; lack of clinical accuracy; cost implications; and the potential clinical, financial, and emotional consequences of falsepositive screening test results. 12 Cost estimates for a national ECG screening program in the United States for

Pediatric Analgesic Clinical Trial Designs, Measures, and Extrapolation: Report of an FDA Scientific Workshop

Analgesic trials pose unique scientific, ethical, and practical challenges in pediatrics. Participants in a scientific workshop sponsored by the US Food and Drug Administration developed consensus on aspects of pediatric analgesic clinical trial design. The standard parallel-placebo analgesic trial design commonly used for adults has ethical and practical difficulties in pediatrics, due to the likelihood of subjects experiencing pain for extended periods of time. Immediate-rescue designs using opioid-sparing, rather than pain scores, as a primary outcome measure have been successfully used in pediatric analgesic efficacy trials. These designs maintain some of the scientific benefits of blinding, with some ethical and practical advantages over traditional designs. Preferred outcome measures were recommended for each age group. Acute pain trials are feasible for children undergoing surgery. Pharmacodynamic responses to opioids, local anesthetics, acetaminophen, and nonsteroidal antiinflammatory drugs appear substantially mature by age 2 years. There is currently no clear evidence for analgesic efficacy of acetaminophen or nonsteroidal antiinflammatory drugs in neonates or infants younger than 3 months of age. Small sample designs, including cross-over trials and N of 1 trials, for particular pediatric chronic pain conditions and for studies of pain and irritability in pediatric palliative care should be considered. Pediatric analgesic trials can be improved by using innovative study designs and outcome measures specific for children. Multicenter consortia will help to facilitate adequately powered pediatric analgesic trials.

Antenatal counselling for parents facing an extremely preterm birth: limitations of the medical evidence.

When physicians are asked for a consult for women in premature labour, they face a complex set of challenges. Policy statements recommend that women be given detailed information about the risks of various outcomes, including death, long‐term disability and various specific neonatal problems. Both personal narratives and studies suggest that parents also base their decisions on factors other than the probabilistic facts about expected outcomes. Statistics are difficult to understand at any time. Rational decision‐making may be difficult when taking life‐and‐death decisions. Furthermore, the role of emotions is not discussed in peri‐viability guidelines.

The OHRP and SUPPORT

A group of medical ethicists and pediatricians asks for reconsideration of the recent Office for Human Research Protections decision about informed consent in SUPPORT.

Should the “Slow Code” Be Resuscitated?

Most bioethicists and professional medical societies condemn the practice of “slow codes.” The American College of Physicians ethics manual states, “Because it is deceptive, physicians or nurses should not perform half-hearted resuscitation efforts (‘slow codes’).” A leading textbook calls slow codes “dishonest, crass dissimulation, and unethical.” A medical sociologist describes them as “deplorable, dishonest and inconsistent with established ethical principles.” Nevertheless, we believe that slow codes may be appropriate and ethically defensible in situations in which cardiopulmonary resuscitation (CPR) is likely to be ineffective, the family decision makers understand and accept that death is inevitable, and those family members cannot bring themselves to consent or even assent to a do-not-resuscitate (DNR) order. In such cases, we argue, physicians may best serve both the patient and the family by having a carefully ambiguous discussion about end-of-life options and then providing resuscitation efforts that are less vigorous or prolonged than usual.

Use of altered informed consent in pragmatic clinical research

There are situations in which the requirement to obtain conventional written informed consent can impose significant or even insurmountable barriers to conducting pragmatic clinical research, including some comparative effectiveness studies and cluster-randomized trials. Although certain federal regulations governing research in the United States (45 CFR 46) define circumstances in which any of the required elements may be waived, the same standards apply regardless of whether any single element is to be waived or whether consent is to be waived in its entirety. Using the same threshold for a partial or complete waiver limits the options available to institutional review boards as they seek to optimize a consent process. In this article, we argue that new standards are necessary in order to enable important pragmatic clinical research while at the same time protecting patients’ rights and interests.

Should All Deaf Children Learn Sign Language

Every year, 10 000 infants are born in the United States with sensorineural deafness. Deaf children of hearing (and nonsigning) parents are unique among all children in the world in that they cannot easily or naturally learn the language that their parents speak. These parents face tough choices. Should they seek a cochlear implant for their child? If so, should they also learn to sign? As pediatricians, we need to help parents understand the risks and benefits of different approaches to parent–child communication when the child is deaf.

Rising preterm birth rates, 1989–2004: Changing demographics or changing obstetric practice?

Preterm birth rates are higher in the United States than in most industrialized countries, and have been rising steadily. Some attribute these trends to changing demographics, with more older mothers, more infertility, and more multiple births. Others suggest that changes in obstetrics are behind the trends. We sought to determine what the preterm birth rate in 2004 would have been if demographic factors had not changed since 1989. We examined complete US birth certificate files from 1989 and 2004 and used logistic regression models to estimate what the 2004 preterm birth rates (overall, spontaneous, and medically induced) would have been if maternal age, race, nativity, gravidity, marital status, and education among childbearing women had not changed since 1989. While the overall preterm births increased from 11.2% to 12.8% from 1989 to 2004, medically induced rates increased 94%, from 3.4% to 6.6%, and spontaneous rates declined by 21%, from 7.8% to 6.2%. Had demographic factors in 2004 been what they were in 1989, the 2004 rates would have been almost identical. Changes in multiple births accounted for only 16% of the increase in medically induced rates. Our analysis suggests that the increase in preterm births is more likely due primarily to changes in obstetric practice, rather than to changes in the demographics of childbearing. Further research should examine the degree to which these changes in obstetric practice affect infant morbidity and mortality.

It's Not the Growth Attenuation, It's the Sterilization!

The doctors and the hospital in the Ashley case made a major error. They should have sought a court order before proceeding with sterilization. Instead, they relied upon ethics committee review. Ethics committee review is inadequate for decisions about sterilization because ethics committees are not open, transparent, or procedurally fair. Sterilization procedures, which are contentious for all the reasons that Diekema outlines in his excellent 2003 review of this controversial issue, require openness, transparency, and procedural fairness (Diekema 2003). Ashley needed and deserved an independent advocate and a public review of her case. The ultimate decision may or may not have been the same. The process would have made all the difference. The ethics committee that reviewed the case, an ethics committee that Diekema chaired, understood this. They recommended that Ashley’s doctors seek judicial review. This wasn’t done. It was a major, inexplicable, and damning transgression. It is odd that Diekema and Fost (2010) now defend that course of action. They do so by giving all the reasons why Ashley’s treatment was morally justifiable. That misses the point. If the reasons for sterilization in Ashley’s case were so compelling as to convince a judge, that would have been all the more reason to seek judicial review. Then, the case could have set a legal precedent for similar cases. As it is, the procedural lapse has led to the opposite result. The case becomes an example of arrogance and secretiveness by doctors and hospitals. It reinforces, rather than challenges, the strong societal prohibitions on sterilization for children like Ashley. In 2003, Diekema argued that involuntary sterilization of persons with mental retardation was only permissible only if “less intrusive and temporary methods for contraception or control of menstruation are not acceptable alternatives, and procedural safeguards have been implemented to assure a fair decision-making process” (Diekema 2003, 25). He seemed to have understood these issues when he chaired the ethics committee that reviewed Ashley’s case and recommended judicial review of the parental request for sterilization. Thus, it is surprising that he and Fost now view judicial review as “an extraordinary proposal with far-reaching implications” (30).