Background on the Preterm Newborn

The preterm newborn is defined as a baby born from 22 to 36 weeks postconceptual age (PCA) [1]. More specifically, preterm is defined by the Center for Disease Control as less than 37 completed weeks of gestation, with early preterm being less than 34 weeks of gestation and late preterm being 34–36 weeks [2]. There were 3.95 million live births in the United States in 2011, with the preterm birthrate declining for the fifth year in a row, with a rate of 11.72 percent of all births being younger than 36 weeks, down from 11.99 percent in 2010 [2]. Overall, 0.7 percent of births in 2011 were babies younger than 28 weeks PCA (Figure 2.1) [3].

Figure 2.1 Total, early, and late preterm birth rates in the United States.

Reproduced with permission from: [2].

Categorization of birth age allows for stratification of risk. Data show that survival is least favorable in the smallest and youngest patients. Recently, with greatly improved accuracy in gestational age (GA) measurements, it has become clear that perinatal complications most closely follow GA, not birth weight. In extremely low gestational age newborns (ELGAN) born at 22–28 weeks PCA, there is improved survival with longer gestation as there is about a 6 percent survival to discharge in a 22-week GA newborn and 92 percent for a 28-week GA newborn [1,4]. The survival in very low birth weight patients has increased since the 1980s due to advances in prenatal, obstetric, and neonatal care, and we now see a majority of infants born at 24 weeks GA survive to leave the hospital (Figure 2.2) [4].

Figure 2.2 Graph of neonatal mortality; survival to discharge.

Reproduced with permission from [4].

Medically intervening in newborns born at 22–24 weeks’ gestation is a controversial area of obstetrics and neonatology and it is not possible to standardize the data available [4]. We see that every week in utero confers better survival as the risk of death is 2.5 times higher in infants born from 24 to 27 weeks compared to those who are born at 28 weeks and more than three times higher for the 22-week newborns [4]. However, morbidity in the survivors is high in the 22–28 week PCA group and one report showed that 93 percent of these patients will have respiratory distress, 46 percent will have patent ductus arteriosis (PDA), 16 percent will have severe intraventricular hemorrhage (IVH), 11 percent will have necrotizing enterocolitis (NEC), and 36 percent will have late sepsis [4]. The most common issues for the smallest of patients are bronchopulmonary dysplasia (BPD) and infections [4]. All of these issues in and of themselves may require surgical attention or add to the anesthetic risk if the patient is taken to surgery. Other common problems that are seen in or result from preterm birth include: retinopathy of prematurity (ROP), hypoglycemia, and neurodevelopmental delay [1,4].

Pediatric anesthesiologists must be vigilant and thoughtful in the provision and planning of care for all of their patients. Preterm newborns who present for surgery are uniquely challenging due to the immaturity of all the organ systems, the complexity of their ongoing medical care, and the often emergent reasons for any surgical procedures. It is unlikely that the surgical issues these patients deal with today will change drastically over the coming years as there seems to be a current plateau in survival [4]. That being said, these patients are usually not cared for on a daily basis by pediatric anesthesiologists and this fact contributes to their challenging care.

Neurologic Issues

Over the past few decades, anesthetic care for preterm newborns has improved as research has allowed us to understand their complex physiology. We have come to learn that fetuses at 20 weeks’ gestation have the neural substrate to transmit impulses due to noxious stimuli. All newborns the pediatric anesthesiologist deals with will require either pain medications or anesthetics to minimize the detrimental stress responses related to surgical procedures [5]. Currently, there are concerns about the long-term neurologic sequelae of exposing the developing brain to anesthetics. This issue is far from resolved and clinical studies are underway that may add to our limited understanding of the effects of anesthetics on the developing CNS. Through vigilant observation and studies, practices are changing to optimize care. There has been recent change in NICU practice to avoid long-term midazolam administration to preterm newborns since this practice has led to the development of choreiform movements in these patients [1,5].

Preterm newborns are at risk for intraventricular hemorrhage (IVH), bleeding from the highly vascular periventricular germial matrix. IVH is multifactorial in nature, and almost 12 000 premature infants develop it every year [4,6]. Preterm newborns are at risk for neuronal injury, whether or not they require surgery, but changes in cerebral blood flow, possibly low or high blood pressure, swings in serum osmolalities, hypercarbia, thrombocytopenia, the presence of PDA, and restlessness are factors that may contribute to IVH [5,6]. The preterm brain lacks the ability to autoregulate blood flow on a consistent basis and this is a prevailing belief that predisposes them to neuronal injury [6]. Lower gestational age, lower birth weight, sicker, ventilated, and clinically unstable infants have been shown to autoregulate cerebral blood flow less well, and mortality is higher in these infants even without IVH [6]. Other types of brain injury are also commonly seen in preterm newborns; the “encephalopathy of prematurity” is a complex amalgam of destructive brain disease as well as maturational and growth dyscrasias affecting this population [7]. One of the most common manifestations is periventricular leukomalacia or disease of cerebral white matter, and its sequelae can be implicated in long-term cognitive and behavioral deficits found in up to 50 percent of formerly preterm newborns [7]. Neuronal damage can be caused by maternal infection, but also can be caused postnatally by sepsis, excitotoxicity, and inability to attenuate free radicals [7]. Also, ventilatory strategies may contribute to or protect infants from neuronal damage. Using pancuronium in intubated newborns to reduce asynchrony from the ventilator has been shown to eliminate fluctuations in cerebral blood flow and decrease risk for IVH [6]. Synchronized intermittent mandatory ventilation and assist control also reduce the fluctuation of cerebral blood flow in infants [6].

Pulmonary Issues

Preterm newborns have a host of respiratory issues that the pediatric anesthesiologist has to deal with, due to maturation, neurologic, chemical, and structural factors.

Respiratory regulation in the preterm newborn can be drastically different from that of the term infant. Postconceptual age is more of a determinant for mature responses to hypoxemia than postnatal age [8]. Periodic breathing occurs in most preterm newborns during REM sleep. Respiration becomes more regular as the newborn matures [8]. The risk of apneic spells is up to 45 percent in infants younger than 48 weeks PCA and more common in younger children [5]. Apnea is defined as cessation of breathing for greater than 20 seconds or cessation of breathing accompanied with a heart rate below 100 bpm, cyanosis, or pallor [5,8]. Preterm newborns are at risk for cardiac arrest if the apnea is prolonged, thus they require close monitoring [8]. Sepsis, intracranial hemorrhage, metabolic acidosis, lack of normothermia, vagal reflexes and anesthetics all contribute to apnea [9]. Preterm newborns may also develop apnea after receiving opiates until around 55 weeks PCA. An additional risk factor for postoperative apnea is a hematocrit of less than 30 percent [1]. An oxygen-enriched environment will promote regular respirations in the preterm newborn and a hypoxic environment will increase apneic spells and respiratory variations [8], which is important with regards to post-anesthesia considerations for the preterm newborn. With vigilance and close monitoring, apnea may be treated with stimulation, bag-mask ventilation, and addition of caffeine or assisted ventilation with continuous positive airway pressure (CPAP) or endotracheal intubation [5]. Obstructive apnea may also occur postoperatively in the preterm newborn due to excessive relaxation [8]. For elective surgeries of the preterm newborn, it is recommended to wait until the newborn reaches almost 60 weeks PCA to decrease this risk of postoperative apnea [5].

Chemical factors also play a critical role in the preterm newborn’s respiratory state. Surfactant, discovered by Dr. Mary Ellen Avery, is a substance that allows small alveoli to remain open in the presence of increased surface tension. Mature surfactant prevents the collapse of smaller alveoli into larger alveoli, thus maintaining functional residual capacity (FRC). Surfactant is made by pneumocytes after 24 weeks’ gestation. The composition changes during gestation and it is not until about 36 weeks’ gestation that there is sufficient mature, functional surfactant to prevent neonatal respiratory distress syndrome (RDS) [5,10]. Respiratory distress syndrome is due to a lack of surfactant, leading to decreased functional capacity [5]. Ninety percent of babies born at 26 weeks will experience RDS [5]. When requiring intubation and ventilation for surgery, these patients experience ventilation perfusion mismatch and may require additional support of PEEP [5]. Ventilation can be difficult and barotrauma and oxygen toxicity are risks of artificial ventilation in this age group; thus it is recommended to use the minimal concentration of oxygen necessary as well as to limit the peak inspiratory pressures used [5]. Because preterm newborns have decreased endogenous surfactant and will often develop respiratory distress, they may be treated with intratracheal surfactant (“surfed”) in the NICU. Intratracheal surfactant has been shown to reduce air leaks, improve survival, and reduce the severity of chronic lung disease [9]. Despite the advantages of surfactant administration, the incidence of BPD in babies treated with surfactant has not been decreased and the use of surfactant in babies born at 28 weeks has decreased in recent years. Bronchopulmonary dysplasia is the requirement of supplemental oxygen at 28 days of life with a chest radiography demonstrating air trapping, atelectasis, and lung field opacification [9]. Assessment of the patient’s respiratory status is important to drive decision-making and treatment plans about the use of surfactant. For example, if the patient is spontaneously breathing, requiring less than 0.4 FiO₂, then using a trial of nasal CPAP may be practiced in favor of intubating and instilling surfactant (Figure 2.3) [4,9].

Figure 2.3 CPAP surfactant.

Source: [9].

Structural lung difference in the preterm newborn also contributes to their more delicate respiratory status. Preterm newborns have reduced lung volumes compared to term newborns. There is a four-fold increase in lung volume and alveolar surface area from 25 weeks to term. Preterm newborns also have a very compliant chest wall, which predisposes them to injury both via volutrauma (pneumothorax) and barotrauma (BPD) when positive pressure ventilation is used [1]. If intubated, NICU strategies are currently incorporating permissive hypercapnea, especially if PIPs are higher than 14–18 cmH₂O, and oxygenation goals are aiming for saturations in the upper eighties to decrease damage to the lungs [1]. A parameter of preterm newborn assisted ventilation is to prevent hypoxia, while at the same time avoiding hyperoxia, and it can be a delicate balance. A low range SpO₂ of 85–89 percent decreased retinopathy of prematurity, but increased mortality, in very low birth weight (VLBW) newborns on supplemental oxygen [9]. Hyperoxia plays a role in decreasing ciliary movement and adversely influencing bronchopulmonary development. The inspired oxygen concentration of oxygen seems to be the main factor, rather than the arterial concentration [9]. PEEP is often utilized in intubated preterm newborns, at around 5 cmH₂O, with the goal of keeping distal airways open to reduce shear stress from when they repeatedly close and reopen, improving oxygenation, and allowing down-titration of inspired oxygen [1,9]. Goal tidal volumes are often in the 6 ml kg^–1 range [1].

One must also consider the small size of the airway when choosing endotracheal tubes. The consideration of cuffed versus uncuffed tubes for risk of subglottic stenosis must be addressed. Also, if a patient is particularly small or requires sophisticated ventilation such as high-flow oscillatory ventilation, it may be beneficial to continue the NICU ventilator in the operating room in order to maintain clinical stability

Cardiac Issues

The preterm newborn is at high risk for cardiovascular compromise when exposed to anesthetic agents and surgery. The physiology of the immature heart consists of poor diastolic function, fixed stroke volumes, and poor autoregulation of the systemic vasculature [5]. Patients administered potent inhalational anesthetics have impaired baroreceptor reflexes and compensate poorly, if at all, for blood loss and hypovolemia [5]. The pediatric anesthesiologist also must have an awareness of congenital anomalies of premature infants as they are 2.4 times more likely to have cardiovascular malformations than term newborns [11]. Preterm newborns are more likely than full-term babies to be born with pulmonary atresia with ventricular septal defect, complete atrioventricular septal defect, coarctation of the aorta, Tetralogy of Fallot, and pulmonary valve stenosis [11]. Also, a majority of preterm infants have a patent ductus arteriosus (PDA) that may require medical or surgical intervention [1,5]. In the term newborn, there is a rapid decrease in pulmonary vascular resistance due to a chemical response to increased pO₂, as well as a reduced pCO₂, and intrapulmonary cardiac and pulmonary pressure changes lead to a quick closure of the patent foramen ovale (PFO) and a PDA [8]. In preterm newborns there is a delay in the response to the increase of arterial oxygenation with extrauterine respirations. When preterm newborns become hypoxic, hypercarbic, or acidotic, they may revert back to a fetal circulation due to a relatively quick increase in pulmonary vascular resistance. This may result in right-to-left shunting via the PFO or opening of the PDA [8]. Monitoring of preductal (right upper extremity) and postductal (lower extremity) saturations is a common intraoperative practice of anesthesiologists that care for the preterm newborn. An open PDA with left-to-right shunting contributes to morbidity in the form of IVH, pulmonary edema and heart failure, NEC, renal insufficiency, or hemorrhage [1].

“Normal” blood pressures are difficult to define in the preterm newborns, but one may review recent blood pressures obtained to have a guide of what “normal” is for a particular patient. Intraoperative blood pressure measurement must use the same size non-invasive blood pressure (NIBP) cuff as was used prior to the trip to the operating room. Hypotension is found in up to 45 percent of premature infants, with hypertension being less common [6]. A common practice among pediatric anesthesiologists caring for patients in this group is to treat the blood pressure if the mean is lower than the GA plus 5 mmHg [5]. Blood pressure treatment can be with colloid, crystalloid, or vasopressors [5]. It is important to note that stroke volume is 1 ml kg^–1 and left ventricular end-diastolic volume is 2 ml kg^–1. Calcium supplementation may be helpful in augmenting blood pressure because preterm newborns have poor calcium reserves and their myocardial function is driven by extracellular calcium [1].