Current Pediatric Reviews (v.9, #1)

Pre-viable Newborns in Saudi Arabia: Where are We Now and What the Future May Hold? by Saleh Al-Alaiyan, Sameer Al-Abdi, Jubara Alallah, Fahad Al-Hazzani, Khalid AlFaleh (4-8).
Rates of population growth, total fertility and birth among the Saudi population are increasing, resulting in more than half a million newborns delivered every year. Despite this significant number of deliveries, there is still an existing shortage in NICU (neonatal intensive care unit) beds in tertiary level hospitals. The percentage of pre-viable newborns in Saudi Arabia is similar to most countries worldwide. We agree that the definition of pre-viability is vague rather than distinct. Recently, a religious opinion regarding resuscitation of pre-viable newborns was issued from Saudi Arabia. It states that for infants born at less than 6 lunar months (252/7 weeks), two specialist physicians could assess the infant's clinical condition at birth and based on their opinion the infant could be offered full resuscitation if it is beneficial to the infant or he or she can be left without intervention to die but should not be deprived of nutrition or fluids. In this review, we compared the outcome of infants less than 1500 grams in three tertiary hospitals in Saudi Arabia with outcome of infants recently published by NICHD. We found that outcomes of these infants born in our tertiary level hospitals are comparable with the outcome of similar groups from NICHD. We strongly believe that clear guidelines are highly needed to support shared decision making to avoid inconsistency in managing ELBW infants at all Saudi hospitals.

Australia is a prosperous, culturally diverse country where respect for quality of life, freedom of speech and religion as well as equal opportunities for all, are values that rank highly amongst society. Its unique physical geography and population distribution continually challenge the health-care system. There are high expectations by both health care providers as well as consumers when emotive issues surrounding the care of a vulnerable infant arise. The care of the periviable infant is one such issue. Moral dilemmas arise from providing intensive care to extremely preterm infants. How far should we, as health care professionals go to preserve life? Should we continue to provide aggressive life-sustaining treatments with the knowledge that there will be some babies and families who will experience significant disability, emotional suffering and financial hardship? In a society such as this, and while uncertainty surrounding survival and morbidity, varying methods of management, and the differing professional and personal views of health professionals, parents, and arbiters of law exist, the care of the peri-viable infant will continue to remain a challenge. This paper aims to describe how Australia's laws and social and medical practices have allowed us to manage infants born in the “grey zone” of viability.

The question of periviability in Italy represents an area of conflict between science, religion and politics. There is an ever widening gap between laws, which are strongly influenced by the Roman Church and the judiciary and the laicism of many Italians, too. From an obstetrical point of view the first contradiction in this field is found in the law that regulates voluntary abortion after the 90th day of pregnancy. An Eugenetic abortion is not allowed. Fetal malformations can not be an indication for abortion, but only in the case the knowledge of this induces a physical or psychical illness in the mother that can worsen with the continuation of pregnancy end. Fetal intra cardiac injection of potassium chloride is not allowed and although the limit in performing an abortion is represented by the possibility for the fetus of having an autonomous life, if there is any possibility of fetal survival, every effort should be done to save the fetal/neonatal life. From a neonatological point of view the kind of care strategies in extremely preterm infants is underlined by a document produced by the National Ministry of Health released on march 08. The consideration that can be drawn from this document is that the science and conscience of a doctor in protecting fetal and neonatal life, continues to be the only indicators in the choices of which kind of assistance a neonate should receive at the threshold of viability, and that the doctor's science and conscience is superior to parental opinion.

Management of Periviable Newborns in the Nordic Countries by Thor Willy Ruud Hansen, Ola Didrik Saugstad (19-24).
Perinatal and neonatal health care is quite uniform in the Nordic countries in spite of large differences in population densities and transport distances. For the present study data was collected with a questionnaire sent to neonatologists in the five Nordic countries Denmark, Finland, Iceland, Norway, and Sweden. In these countries there are totally approximately 80 level II and 25 level I NICUs. Care of periviable immature infants is strongly centralized with a few exceptions in Norway due to long transport distances. Iceland with one level III NICU only is the only country with national guidelines for management of prematurity, and only Norway has national guidelines for follow-up. In all countries the lower margin of viability is considered as < 23 weeks, although practical handling of these smallest children may vary between countries and within each country. In parts of Sweden proactive management is recommended while other units, for instance in Denmark, practice palliative care at 23 weeks and life support at 24 weeks. Following a consensus conference organized in Norway in 1998 it became common practice to treat babies with gestational age down to 23 weeks, however parental choice and autonomy should be respected. This seems to be in accordance with recent international guidelines. In summary, ELBWI are offered intensive care treatment in all Nordic countries but with some variation between countries concerning rate of referral and degree of centralization of care. Survival rates for these babies are quite high in all the Nordic countries.

The Premature Lottery in the Canadian Grey Zones by Annie Janvier, Prakesh S. Shah (25-31).
Canada is a large country with only 34 million inhabitants. Canada has a socialized healthcare system and a prematurity rate between 7 and 8%. Interventions for extremely low gestational age infants (ELGANs) raise ethical concerns in many countries. Unlike the physiologic limit of viability, which is about 22 weeks and is similar around the globe, the borders of the “grey zone” for ELGANs range between 21 to 26 weeks, depending where the baby is born. The borders of the gray zones are fuzzy, elastic and subjective. We will explore variation of practice for ELGANs both around the world and in Canada. We will come to several conclusions 1. Policy statements for ELGANs based uniquely on gestational age are scientifically problematic and should be avoided; 2. Policy statements for ELGANs might reflect the fact that ELGANs are considered to be morally different from older children; 3. Variation of practice (and outcomes) for ELGANs may reflect values more than facts, and facts in turn can influence values; 4. National databases, such as the Canadian Neonatal Network, are invaluable tools in evaluating and studying variation of practices for ELGANs; 5. Physicians can learn from these variations of practice, but this demands humility, curiosity and open mindedness; 6.The increase in preterm birth rates should be seen as an emergency in all countries.

The United States is the largest country in the ‘industrialized world’, and, as such, has dominated the medical literature reporting practices and outcomes of neonatal intensive care. Perhaps surprisingly, very few things about U.S. Neonatology are unique to the U.S. This chapter will attempt an impossible task - summarizing the practice of neonatology in the entire U.S. I will draw parallels to practices of my colleagues around the globe, and point out American idiosyncracies where they arise. I will end with my sense of the likely (at least in the near-term) future developments for neonatology in the U.S.

Coping with the Dilemmas of Extremely Preterm Birth: Outcome or Ethics? by Umberto Simeoni, Dominique Haumont (36-39).
Overtreatment in extreme prematurity, is an ongoing debate and often translated as ‘what are the limits of viability?’ The concerns stemming from this issue are the risks of long-term morbidity and mortality. Although many medical specialties are concerned with overtreatment, in neonatology and especially in extreme prematurity, the paradox of the emotional impact of happiness of a new life and fear about worrying outcome issues is absolutely unique. Many discussants have asked for defining therapeutic limits in extreme prematurity. Statistical approaches from epidemiologic outcomes have oversimplified those limits in terms of criteria as simple as gestational age or birth weight. Current scientific, epidemiologic and medical-economic knowledge have demonstrated the complexity of the issue. For example, in recent years, these infants have required intensive care less often than in previous years. Gestational age alone has been shown to be a poor prognostic factor for both mortality and severe morbidity. Recently more complex models have been proposed including more relevant prognostic risk factors like chorioamnionitis, prenatal steroids or gender. Furthermore, the absolute number of preterm infants increases significantly with increasing gestational age. The impact on public health resources of late preterms, who are not concerned by futile treatment issues, is much more important compared to extreme preterm infants. But, the emotional and symbolic aspects of periviability are dramatic and very complex. Ethical and medical dilemmas in decision making around withholding or withdrawing treatment will be strongly influenced by the underlying culture, economic situations of countries and individual spiritual believes of both caregivers and families.

A substantial number of reports and studies in the last 10-15 years have described the physician's attitude towards neonatal EoL decisions and medical practice in the Netherlands. Legal developments have supported the concept that the decision to withholding and withdrawing life-sustaining treatment in newborns can be regarded normal medical practice. Deliberate ending of life, however, is labeled as an extraordinary category of medical actions, both medically and legally, that requires reporting and review as described in the Groningen Protocol. A recent study has indicated that reports have become increasingly rare. This might be because deliberate life-ending has become virtually non-existent, or it might still occur unreported because it’s unclear to the physicians where the demarcation between ‘good’ palliative care and deliberate life-ending lies. The medical profession should and could work together to get this issue cleared up.

The advancement in neonatal medicine in the past several decades is characterized, among other parameters, by the increasing provision of intensive care to preterm newborns. Understanding the ethical issues arising throughout the provision of intensive care for extremely premature newborns in different gestational ages is an essential step in the process of developing recommendations or guidelines on a national level, regarding the care of those patients. In Israel, a relatively high birth rate, low infant mortality rate and a significant premature infant birth rate make policy-making in this area particularly challenging. In this paper we focus on ethical dilemmas and decision-making issues which the Israeli health care team encounters when dealing with the desired approach to the care of premature infants at the border of viability. We start by a brief description of the current situation in Israel in regard of birth and prematurity. We then move on to discuss the legal, moral and social status of the fetus and newborn in Israel. The heart of this paper is a review of the existing guidelines and statutes regarding the care for extremely premature newborns in Israel and the ethical and decision- making issues it brings into the table.

This paper examines the differences between different countries in policies regarding babies born at the borderline of viability. Such differences clearly exist. It is unclear whether they exist, in such an explicit way, for other populations of patients. Differences seem to reflect both the unique cultural milieu of different countries and also the unique moral status of the peri-viable baby. Similar differences exist regarding the moral status of the fetus. Such differences are likely to increase as fetal medicine develops, and the line between intrauterine and extrauterine life becomes less distincts.

Persistent pulmonary hypertension of the newborn (PPHN) remains a serious disorder with significant mortality and long term morbidity. Inhaled nitric oxide is the only approved vasodilator therapy in neonates, but 40% of infants are non-responders. Recent biological evidence has enhanced our understanding of the cellular mechanisms involved in cardiopulmonary transition at birth, paving the way for potential alternate therapies as published in recent reviews. Optimal clinical care of infants with PPHN necessitates a comprehensive understanding and evaluation of cardiopulmonary hemodynamics. Targeted neonatal echocardiography (TnECHO) is increasingly being implemented to guide clinical decision making. The purpose of this review is to outline the role of TnECHO in better defining the cardiopulmonary physiology in PPHN and its application in clinical practice. In addition we briefly review the physiology, pathogenesis and novel therapeutic agents currently under investigation for management of PPHN.

The administration of antenatal glucocorticoids to women in preterm labour confers clear and significant benefits on perinatal outcomes, decreasing the incidence of respiratory distress syndrome and intraventricular hemorrhage in preterm babies, thereby reducing rates of mortality and morbidity. However, there is an evolving body of research addressing the non-pulmonary consequences of antenatal glucocorticoid administration, particularly in the growth restricted fetus. In particular, synthetic glucocorticoids, such as betamethasone and dexamethasone, are strong modulators of vascular structure and function such that antenatal glucocorticoids may have profound and lasting effects on fetal/neonatal cardiovasculature. This review examines the clinical and experimental literature on the benefits and risks of antenatal glucocorticoids in the well-grown preterm infant and in infants affected by intrauterine growth restriction (IUGR), highlighting the significant lack of specific information on the effects of antenatal glucocorticoids in IUGR infants. This is important because IUGR is associated with preterm birth and so the IUGR fetus is likely to be exposed to antenatal glucocorticoids. Recent experimental studies have shown that the fetal hemodynamic actions of exogenous glucocorticoids are profoundly different in IUGR fetus compared with the well-grown fetus with possible adverse implications for the development of the immature brain. Such observations merit caution clinically and further investigation.

Steroids and Vasopressor-Resistant Hypotension in Preterm Infants by Manoj Biniwale, Smeeta Sardesai, Istvan Seri (75-83).
Despite our inability to appropriately define the gestational- and postnatal-age dependent normative values of blood pressure, hypotension is often been diagnosed and treated in preterm neonates especially during the transitional period. Although the perceived normal blood pressure values can be restored in the majority of preterm neonates by administration of volume and vasopressor-inotropes, some patients will not respond even to higher doses of vasoactive medications. In these neonates with so-called “vasopressor-resistant hypotension”, steroid administration is usually effective in increasing the blood pressure to the perceived normal range and decreasing vasopressor requirement. The etiology of vasopressor-resistant hypotension is thought to be a combination of transient adrenocortical insufficiency of prematurity and downregulation of the cardiovascular adrenergic receptors. In the clinical practice, hydrocortisone is used most frequently for the management of vasopressor-resistance. Importantly, low-dose hydrocortisone appears to improve blood pressure without compromising cardiac function or systemic perfusion in these patients. However, caution must be exercised when hydrocortisone is administered during the first postnatal week as significant side effects including gastrointestinal perforation may occur especially in infants co-exposed to indomethacin. In addition, although the available data on the lack of a documented impact of early low-dose hydrocortisone administration on brain development are encouraging, more and appropriately powered studies are needed to put this concern to rest.

Neonatal Ultrasound in Transport by Kathryn Browning Carmo, Nick Evans, Martin Kluckow, Andrew Berry (84-89).
Current practices for monitoring the haemodynamics of critically ill newborns whilst in transport to tertiary care are poorly validated. These include arterial blood pressure monitoring, capillary return and urine output. Clinician performed ultrasound (CPU) has been validated in the NICU and is currently being trialled in transport. This case based discussion describes the retrieval of four newborn infants utilising CPU assessment of the newborn systemic blood flow and investigation of intracranial blood flow and pathology. Case one describes a baby with subgaleal haemorrhage who was pre arrest where the CPU (cardiac) allowed the treating team to effectively change the inotropes and alter the clinical course. Case two is a baby with the classical diagnostic dilemma of persistent pulmonary hypertension of the newborn (PPHN) versus cyanotic congenital heart disease (CCHD) – the screening CPU (cardiac) was able to define CCHD and the transport was re-directed to tertiary paediatric cardiac services. The CPU (cardiac) in case three, a baby born at 25 weeks, also assisted in the choice of therapeutic options for the treating team. Both case three and four were born at 25 week gestation and the CPU (cranial) provided information prior to transport that aided in the counselling of the parents.

The first 24 hours of a preterm infant’s life is often a period of cardiovascular instability. A complex relationship exists between the heart, brain and systemic and cerebral vasculature and in the immediate neonatal period in which low blood pressure, low systemic blood flow and low cerebral blood flow are common. The preterm infant is at risk of low systemic blood flow (and low blood pressure) due to a combination of intrinsic factors (immaturity of the preterm myocardium and vasculature) as well as extrinsic factors (including mechanical ventilation and vasoactive medications). Low systemic blood flow is common in preterm infants and contributes significantly to the perinatal brain injury, which manifests as peri/intraventricular haemorrhage (P/IVH) and white matter injury. These in turn contribute to the significant neurological and/or developmental disabilities in survivors that impact long term on their quality of life. This paper will look at the evidence currently available for the management of low systemic blood flow in preterm infants.