Emergencies in the First Week of Life

AUTHORS

Garrett Thompson, MD, MPH, Emergency Medicine Resident, Department of Emergency Medicine, Penn State Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA

Stephen M. Sandelich, MD, Assistant Professor, Departments of Emergency Medicine and Pediatrics, Penn State Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey, PA

PEER REVIEWER

Steven M. Winograd, MD, FACEP, Attending Emergency Physician, Trinity Healthcare, Albany, NY

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The first week of life is a critical period for newborns, marked by rapid physiological transitions and a heightened vulnerability to various medical emergencies. This article provides an in-depth exploration of several significant neonatal emergencies that can arise during this time, including respiratory distress syndrome (RDS), congenital heart defects, sepsis, duodenal atresia, vitamin K deficiency bleeding, necrotizing enterocolitis (NEC), intestinal malrotation, and congenital adrenal hyperplasia (CAH).

Each condition presents unique diagnosis, management, and prognosis challenges, demanding prompt and precise medical intervention to optimize outcomes. By examining the latest research and clinical guidelines, this article aims to equip emergency physicians with the knowledge to effectively address these emergencies, thereby improving neonatal survival and long-term health.

Neonatal Respiratory Distress Syndrome

Neonatal respiratory distress syndrome (RDS) is a common cause of respiratory failure most often presenting hours after birth secondary to lack of lung surfactant production. The condition affects approximately 10% of late preterm neonates and 1% of term neonates, but it is seen most in infants who are born before 32 weeks’ gestation.^1,2 Mortality ranges between 5% and 10%, with increased rates at lower gestational ages.³

The etiology of RDS is a lack of pulmonary surfactant secondary to insufficient formation, decreased activity, or destruction/inactivation.⁴ It is seen in premature infants because they lack adequate production of surfactant, but it also can be seen in some autosomal genetic disorders that result in the production of ineffective surfactant.⁵ Genetic surfactant disorders often require lung transplantation.

Pulmonary surfactant decreases surface tension within the alveoli and increases overall lung compliance. Decreasing the surface tension allows the alveoli to remain open during expiration, which, in turn, allows adequate lung ventilation.⁵ Pulmonary collapse damages lung parenchyma and leads to an inflammatory response, similar to acute respiratory distress syndrome (ARDS), which leads to pulmonary edema and further surfactant dysfunction and oxygenation issues.⁴

The most significant risk factor for RDS is prematurity. Cesarean delivery, male gender, small size for gestational age, maternal-fetal infection, multiparity, and gestational diabetes have been associated with increased risk of RDS.^6,7 These patients can present to an emergency department in the setting of non-hospital births or may present after being initially diagnosed at birth, but this is less likely. Out-of-hospital births have been uptrending and now make up approximately one in 62 births in the United States.⁸

Generally, patients present immediately after birth with respiratory distress. On exam, patients will have signs of respiratory distress, including cyanosis, retractions, tachypnea, tachycardia, grunting, and nasal flaring. Decreased breath sounds will be heard on auscultation secondary to atelectasis. If untreated, RDS can progress to respiratory failure.

Diagnosis of RDS is clinical, using elements from the history and physical exam as well as diagnostic testing, including chest X-ray and arterial blood gas that, when considered together, can point toward a diagnosis of RDS. Chest X-ray findings include homogenous ground glass shadowing, air bronchograms, and alveolar shadowing.⁹ Arterial blood gas will show hypoxemia and hypercarbia.

The differential diagnosis for RDS includes congenital cardiac defects, transient tachypnea of newborn, meconium aspiration, pulmonary hypertension, airway malformation, inborn errors of metabolism, and infection.

Given the severity of RDS, it is essential to recognize and treat the condition immediately. The European Consensus Guidelines on the management of respiratory distress syndrome, last updated in 2022, recommend the following: use of natural surfactant given by the less invasive surfactant administration (LISA) technique, which may be repeated up to three times; use of T-piece devices rather than bag valve masks; use of continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NIPPV); use of lung protective modes for mechanical ventilation if required (when NIV fails); use of caffeine for infants > 32 weeks to prevent mechanical ventilation; and targeting oxygen saturation of 90% to 94%.¹⁰

When administering surfactant, it must be directly introduced into the trachea. The preferred method, LISA, involves the use of a small catheter while the neonate remains spontaneously breathing to introduce surfactant into the trachea. Other methods, such as the intubation–surfactant–extubation (InSurE) technique, can lead to a harmful inflammatory response.¹¹ Multiple types of surfactants are commercially available, but there does not appear to be a clinically significant difference between them.¹² Early initiation of positive pressure ventilation has been found to reduce the intubation rate.¹³

Patients with RDS should be admitted to the neonatal intensive care unit (NICU) to be appropriately monitored and managed. Transfer to a facility with appropriate resources may be necessary. With adequate support, surfactant production begins endogenously.¹⁴ The typical course of RDS is approximately three days, and most patients do well with appropriate treatment.¹⁵

In summary, RDS is a common cause of respiratory distress, especially in preterm infants, which results from the lack of functioning surfactant production. Lack of surfactant leads to alveolar collapse and respiratory compromise. The diagnosis is clinical. Treatment should be started immediately with supplemental oxygen and surfactant. If treated appropriately, outcomes generally are good.

Congenital Heart Defects

Congenital heart defects (CHD) encompass a wide range of structural defects to the heart and great vessels that are present at birth with varying severity.

In North America, the incidence of CHD is 1,229 per 100,000 live births. It is the No. 2 cause of death for infants in countries in the global north.¹⁶ In the United States, the overall mortality secondary to CHD has declined over the past two decades.¹⁷

Most often, the defects found in CHD arise during embryogenesis due to a mix of genetic and environmental factors, such as teratogenic substances, viruses, and ionizing radiation.¹⁸ The risk of CHD is associated with low maternal education, pregestational diabetes, maternal clotting disorders, nutritional deficiencies, infections, and medications, such as retinoic acid, antidepressants, and anti-epileptic medications.^18-20 CHD can arise as an isolated cardiac defect or as part of a syndrome involving multiple organ systems, such as DiGeorge syndrome. (See Table 1.)

The pathophysiology of CHD varies based on the specific structural defects. Broadly, CHD is categorized into cyanotic and acyanotic defects. (See Table 1.) Cyanotic defects are the most serious given their potential to cause significant hemodynamic compromise and cardiovascular collapse. Cyanotic defects result in the shunting of poorly oxygenated blood from the right ventricle to the left ventricle, leading to hypoxemia. Cyanotic heart defects can be remembered with the five Ts: truncus arteriosus, transposition of the great arteries, tricuspid atresia, tetralogy of Fallot, and total anomalous pulmonary venous return.

Cyanotic heart defects are further stratified by whether they are dependent on a patent ductus arteriosus (PDA) to maintain perfusion. This is an important distinction because it can affect emergent management. The ductus arteriosus, a remnant of the fetal circulatory system, begins closing 48 hours after birth and generally completely closes at two weeks.²¹ For ductal-dependent lesions, including tetralogy of Fallot, transposition of the great arteries, and in certain cases of tricuspid atresia, closure can result in significant cardiogenic shock and can require temporizing intervention with medications to maintain a PDA.²¹

Ductal-dependent CHD typically manifests when the circulatory system transitions from fetal to neonatal circulation with the closure of foramen ovale, ductus arteriosus, and ductus venosus. These shunts serve to bypass the fetal lungs and liver. This transition generally begins immediately at birth.²² This subtype of cardiac defects is dependent on the PDA, which connects the aorta and pulmonary artery, and manifests with its closure after birth (48 hours to two weeks).

Obstructive CHD, a further subtype involving both cyanotic and acyanotic lesions, creates pressure gradients across the cardiovascular flow system. Lesions affecting the left heart include bicuspid aortic valve, aortic stenosis, coarctation of the aorta, hypoplastic left heart syndrome, and interrupted aortic arch.²³ Lesions affecting the right heart include pulmonary stenosis, pulmonary hypertension, and tricuspid regurgitation commonly seen in Ebstein’s anomaly.²⁴ Although most cases of acyanotic obstructive CHD do not cause critical illness during the neonatal period, patients presenting with heart failure may require urgent surgical intervention.²⁵

Non-obstructing acyanotic lesions, such as atrial septal defects (ASD), ventral septal defects (VSD), and atrioventricular septal defects (AVSD), can present individually or as part of a syndrome. Their implications on hemodynamic dysfunction can vary, and their treatment generally depends on their severity.²⁶

Cyanotic CHD generally presents within the first few days of life with nonspecific symptoms, such as skin color changes, difficulty feeding, irritability, and issues with gaining weight. Obstructive acyanotic CHD can present similarly but without skin changes that would be indicative of cyanosis.

On physical exam, cyanosis is a prominent feature and often is seen centrally. Cyanosis rarely can affect the pre-ductal and post-ductal areas of circulation differently, resulting in “differential cyanosis” or “reverse cyanosis” in which parts of the body appear well perfused while the remainder of the body is poorly perfused.^27,28 Hypoxia generally is noted and is not responsive to supplemental oxygen as the cardiac shunt bypasses the lungs. Cardiac murmurs may be heard, but these can be difficult to appreciate on neonates.

In cases of obstructive CHD, patients can have significant pulmonary abnormalities, such as tachypnea or increased work of breathing secondary to pulmonary edema in the setting of heart failure. This is not seen in non-obstructive cyanotic CHD.

In patients in whom a ductal-dependent defect is suspected, intravenous prostaglandin E1 (PGE1) should be administered at a rate of 5 ng/kg/min to
10 ng/kg/min, which can be titrated every 20 minutes according to the patient’s response to a maximum of 100 ng/kg/min.^29,30 Improvement is assessed by increased oxygenation (in cyanotic CHD) and increased blood pressure (BP) in acyanotic CHD. It is important to monitor for apnea, which can be a potential side effect of PGE1, occurring in up to 10% to 12% of recipients. If apnea develops, intubation is required. Other adverse effects include hypotension, hyperthermia, hypoglycemia, tachycardia or bradycardia, and seizures. The goal is to use the lowest effective dose.

Because of the potential for apnea, the decision to intubate prior to transportation should be weighed while considering factors such as transport time and skill and experience of transporting providers. One retrospective study found that elective intubation of infants of PGE prior to transport did increase the risk of major transport complication without significant improvement in outcomes.³¹

CHD generally are identified on prenatal ultrasound scans, but approximately 1.9% of all births have no prenatal care and, therefore, may present to an emergency department with undiagnosed CHD.³² The definitive diagnosis for CHD is a transthoracic echocardiogram (TTE), performed by an individual with expertise in pediatric cardiology, but this often is impractical and unavailable in the emergency department.³³ Per the American Society of Echocardiography, point-of-care ultrasound (POCUS) may incidentally identify some features of CHD but should not be used to diagnose and aid in the diagnosis of CHD.

Testing such as chest X-ray, electrocardiogram (ECG), and blood gases can help evaluate for CHD in the emergency department. (See Table 2.) ECG findings such as right atrial dilation (RAD), right ventricular hypertrophy (RVH), biphasic wide QRS complexes, and acute pointed elevated P waves can be indicative of CHD.³⁴ Chest X-ray may show cardiac silhouette abnormalities, including cardiomegaly, right atrial enlargement, and right-sided aortic arch, but also condition-specific abnormalities such as a “boot shaped” heart seen in tetralogy of Fallot.³⁵ An arterial blood gas (ABG) with low pO₂ and that is not responsive to 100% oxygen administration can indicate the hypoxia is cardiac in origin.²⁸

Differential diagnoses include methemoglobinemia, pneumonia, pulmonary hypertension, pneumothorax, respiratory distress syndrome, congenital airway/pulmonary anomalies, and neurologic disorders.

Early transfer to a tertiary care center capable of handling these complex pediatric patients should be initiated immediately upon recognition/suspicion of CHD. It is common for neonates with CHD to have severely depressed oxygen saturations.²⁹ Supplemental oxygen will not correct the hypoxemia because it is secondary to a shunt issue. If respiratory/airway compromise and/or hypercarbia is present, more aggressive measures, such as mechanical ventilation, may be necessary.

In summary, CHD is a set of anatomic defects affecting the heart and great vessels present at birth that may lead to shunting of poorly oxygenated blood from the right to left side of the heart, bypassing the lungs and causing significant hypoxia. Neonates often will present with respiratory distress and hypoxia, which often is not responsive to supplemental oxygen. Early recognition with PGE administration, if appropriate, and transfer to a pediatric center capable of managing CHD is important.

Intestinal Malrotation and Volvulus

Malrotation refers to an abnormal rotation and fixation of the intestines during fetal development, which can predispose the intestines to twist around the superior mesenteric artery, resulting in volvulus. Volvulus is a surgical emergency characterized by a complete twisting of the bowel, leading to compromised blood flow, ischemia, and potentially necrosis of the affected bowel segment. Prompt recognition and intervention are crucial to prevent severe morbidity and mortality associated with this condition.³⁶

The incidence of intestinal malrotation is estimated to be approximately one in 500 live births, with volvulus occurring in about one in 6,000 live births. These conditions can present at any age but most commonly are diagnosed in the neonatal period, with most cases presenting within the first month of life. The mortality rate for volvulus remains significant, ranging from 5% to 15%, mainly depending on the timeliness of diagnosis and surgical intervention.³⁷

The etiology of malrotation involves errors in the normal embryological process of gut rotation and fixation. During the sixth to 10th weeks of gestation, the midgut undergoes a complex rotation around the superior mesenteric artery. Failure of this process can result in various anatomical anomalies, including malposition of the cecum and the formation of Ladd’s bands, which can obstruct the duodenum and predispose to volvulus.

The twisted bowel in the volvulus compromises the blood supply, leading to bowel ischemia and necrosis. If not promptly addressed, the compromised blood flow can progress rapidly to sepsis and shock. The intestines’ involvement in this condition can vary, with the midgut most commonly affected.

Clinically, neonates with malrotation and volvulus typically present with acute bilious vomiting, which is a hallmark symptom and should raise high suspicion for volvulus. Other presenting symptoms include abdominal distension, irritability, lethargy, and signs of shock, such as tachycardia and hypotension. Physical examination may reveal a distended, tender abdomen and, in severe cases, peritonitis.

An upper gastrointestinal series is the gold standard for diagnosing malrotation and volvulus, demonstrating an abnormal position of the duodenojejunal junction and the classic “corkscrew” appearance of the twisted bowel.³⁸ Abdominal ultrasound also may be used to assess for the “whirlpool sign,” indicative of midgut volvulus.³⁹ In cases of suspected volvulus, immediate surgical consultation and intervention are imperative.⁴⁰

The differential diagnosis for neonatal bilious vomiting includes conditions such as duodenal atresia, Hirschsprung disease, meconium ileus, and necrotizing enterocolitis. However, the acute presentation and rapid deterioration associated with volvulus necessitate prioritizing its diagnosis and management.

Management of malrotation and volvulus requires emergent surgical intervention. The definitive treatment is the Ladd procedure, which involves detorsion of the volvulus, division of Ladd’s bands, broadening of the mesentery, and placement of the bowel in a non-rotated position.

Preoperative stabilization with intravenous (IV) fluids, electrolyte correction, and nasogastric decompression is critical. These patients may be severely dehydrated, and third spacing is common. Aggressive fluid resuscitation with normal saline in 20 mL/kg increments, up to 60 mL/kg, often is required. Fluid resuscitation should be targeted to clinical and hemodynamic improvement. If patients continue to remain unstable after adequate resuscitation, vasoactive medication may be required.

Broad-spectrum antibiotics also are administered to prevent or treat sepsis. Appropriate antibiotic choices include piperacillin-tazobactam (240 mg/kg/day to 300 mg piperacillin/kg/day divided every six to eight hours), or ceftriaxone (50 mg/kg/day to 100 mg/kg/day divided every 12 to 24 hours) and metronidazole (30 mg/kg/day to 40 mg/kg/day in divided doses every eight hours).

Postoperative care includes close monitoring in a neonatal intensive care unit, with attention to potential complications such as short bowel syndrome, which may result from extensive bowel resection. Long-term follow-up is essential to monitor growth, development, and gastrointestinal function.

In summary, intestinal malrotation and volvulus are critical neonatal emergencies characterized by abnormal intestinal rotation and potential bowel ischemia. Prompt recognition, rapid diagnostic evaluation, and emergent surgical intervention are essential to prevent severe complications and improve outcomes.

Intestinal Atresia

Intestinal atresia is the congenital narrowing of the intestinal tract, most commonly the duodenum, resulting in obstruction. Atresia is the complete obstruction of the intestinal lumen, whereas stenosis is the partial obstruction. Small bowel atresia occurs in approximately 3.4/10,000 births in the United States.⁴¹ Overall, the mortality and morbidity of intestinal atresia is favorable, with complications such as cardiac anomalies and short gut syndrome driving most of the mortality/morbidity.⁴² Duodenal atresia has the highest rates of mortality, whereas colonic atresia has the lowest rates.

Down syndrome often is associated with duodenal atresia, with up to 25% of neonates with the condition having Down syndrome. Additional studies have found a correlation between young maternal age (< 20 years) and small bowel intestinal atresia.⁴³ It is hypothesized that atresia arises as a result of either recanalization failure or intestinal ischemia during embryogenesis.⁴⁴

Symptoms generally are present within the first 24 hours of life. Bilious vomiting is seen in the vast majority of cases. In cases of delayed presentation, recurrent vomiting, failure to gain weight, and dehydration can be seen.^45,46 Abdominal distension may or may not be present. Distension is more common with atresia of the jejunum and colon than with the duodenum. Polyhydramnios may be noted prenatally.

Abdominal X-ray imaging is crucial to the diagnosis of intestinal atresia. In duodenal atresia, the classic “double bubble” sign may be seen on abdominal X-ray in which both the stomach and first part of the duodenum are dilated. (See Figure 1.) In more distal cases of atresia, bowel distention also will be present. Other studies, such as upper gastrointestinal contrast studies, are less useful but may help rule out malrotation.⁴⁶ Barium enemas may help differentiate between a large and small bowel obstruction in cases that are not clear.⁴⁶ Additionally, during this workup, it is important to obtain basic laboratory work to assess for hypoglycemia, electrolyte abnormalities, and renal insufficiency.

The differential diagnosis for neonatal bilious vomiting includes conditions such as volvulus, Hirschsprung disease, meconium ileus, incarcerated hernia, imperforate anus, and necrotizing enterocolitis.

Intestinal atresia at any point along the intestinal tract is a surgical emergency. Prior to surgery, decompression of the stomach with either an oral gastric (OG) or nasogastric (NG) tube should be performed, IV fluids should be administered, along with IV antibiotics, and electrolytes should be corrected as warranted.⁴⁷ In cases of duodenal atresia, a preoperative echocardiogram to rule out any cardiac abnormalities that would complicate surgical intervention may be warranted given its association with Down syndrome.

Patients with intestinal atresia require immediate surgical correction and admission to the hospital under a pediatric surgical service. They may require transfer to a hospital with appropriate pediatric surgical resources.

In summary, intestinal atresia is the congenital obstruction of the intestinal lumen that generally presents within the first 24 hours of life with bilious vomiting. Diagnosis is based on abdominal imaging, generally with plain films. Treatment in the emergency department is supportive with decompression and fluids, but ultimately these are temporizing measures because these patients require definitive surgical intervention.

Vitamin K Deficiency Bleeding

Vitamin K-dependent clotting factors, including prothrombin, FVII, FIX, protein C, and protein S, play an integral role in the clotting cascade.⁴⁸ A deficiency of vitamin K, which can be seen in neonates due to the low quantities of vitamin K in breast milk and poor placental transfer of vitamin K, can increase the risk of serious bleeding.⁴⁹ It should be noted that most formulas supplement with vitamin K. The American Academy of Pediatrics recommends that all neonates be given intramuscular (IM) vitamin K within 24 hours of birth. More recently there has been an increased trend in parental refusal and, therefore, a rise in the rate of neonatal bleeding.⁴⁹

There are three types of vitamin K deficiency bleeding (VKDB): early onset, classic, and late. Early onset occurs within the first 24 hours of life and generally is found in neonates whose mothers took medications that alter vitamin K metabolism.⁴⁹ Classic VKDB occurs one to seven days after birth, whereas late onset occurs after one week of birth and generally is due to vitamin K malabsorption.⁵⁰ This article will focus on classic VKDB.

There are few data reporting the overall incidence of VKDB, most likely because IM vitamin K, which is the standard of care, is highly effective at reducing instances of VKDB.⁵¹ In cases where prophylactic vitamin K is not delivered, the incidence of VKDB ranges from 250 to 1,700 per 100,000 births.⁵² The rate of prophylaxis refusal is up to 3.2% for in-hospital births, 14.5% for home births, and 31% in birthing centers.⁵² Reasons that parents refused the vitamin K included the concern that vitamin K administration would pose risks to the neonate, religious beliefs, and preference for what parents believed to be alternative supplementation.⁵² One study estimated that the relative risk of VKDB in neonates who did not receive vitamin K is 81 times that of a neonate who did receive prophylaxis.⁵³ Limited large-scale studies exist for outcomes in cases of VKDB for infants who did not receive prophylactic vitamin K, but one review that analyzed numerous case reports and case series found a mortality rate of 20.5% and that 9.8% of patients had significant neurologic disabilities.⁵²

VKDB presents with difficult to control/severe bleeding. Sites of bleeding vary. Cases of early VKDB are more prone to intracranial, intra-thoracic, and intra-abdominal sources of bleeding, whereas classic VKDB generally have less severe forms of bleeding, including from the gastrointestinal tract, skin, and commonly at the site of circumcision.⁵¹

VKDB should be suspected in any neonate who did not receive prophylactic vitamin K who presents with significant bleeding, especially in cases of exclusive breastfeeding. If the bleeding is severe, treatment should be started immediately. In less severe cases, a coagulation panel may help diagnose the condition with an international normalized ratio (INR) > 4 and prothrombin time (PT) > x 4 the control.⁵⁴ The British Pediatric Surveillance Unit developed the following definition used for retrospective data collection: “Any infant under 6 months of age with spontaneous bruising/bleeding or ICH associated with prolonged clotting times (PT at least twice control value) and normal or raised platelet count, NOT due to an inherited coagulopathy or disseminated intravascular coagulation.”⁵⁵

The differential diagnosis for prolonged, difficult to control bleeding includes genetic bleeding disorders, acquired bleeding disorders, liver dysfunction, uremia, and disseminated intravascular coagulation.

Management of VKDB should be the early administration of phylloquinone (vitamin K1) at 300 mcg/kg, but it may need to be increased in the setting of medications that affect vitamin K metabolism.⁵¹ One small study found that phylloquinone can act rapidly with significant impacts on PT within the first hour after administration.⁵⁶ If bleeding is severe, clotting factors such as fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC) should be transfused.

Patients with VKDB associated with significant bleeding should be hospitalized for further monitoring and specialist intervention if warranted.

In summary, VKDB is a rare bleeding disorder associated with lack of prophylactic vitamin K administration at birth. Lack of prophylaxis is common in births occurring at home or at birthing centers and is increasing. VKDB should be suspected in cases of bleeding from infants who did not receive vitamin K prophylaxis and should be treated appropriately with phylloquinone at
300 mcg/kg.

Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is an emergent condition driven by inflammation within the gastrointestinal tract leading to necrosis. There is an emerging consensus that NEC represents several distinct disease processes culminating in bowel inflammation.⁵⁷

Among very low birth weight (VLBW) infants, approximately 7.6% develop NEC based on one large cohort study.⁵⁸ The overall mortality for NEC is approximately 17.4%.⁵⁹ Rates of mortality were higher among Black neonates than white neonates.⁶⁰ Morbidity is highly variable and dependent on the severity of NEC, with studies finding rates of neurologic disability between 25% and 61% and rates of intestinal failure between 15.2% and 35%.⁵⁹

The pathophysiology of NEC is multifactorial and not completely understood. Multiple environmental factors are thought to contribute, but it appears that most cases are related to inappropriate activation of inflammatory pathways, likely in response to dysbiosis of the intestinal microbiome.⁶¹

NEC is most common in preterm infants, but 10% of cases occur in term infants who tend to have underlying medical conditions.^62,63 Mean age at presentation was found to be 7 days for early onset NEC.⁶⁴ Early presentation of NEC generally is nonspecific with many overlapping features of sepsis. Refusal of feeding often is an early sign. Other signs can include vomiting and bloody stools.⁶⁵ Abdominal findings on physical exam often are seen when NEC is advanced and include abdominal distension and a shiny appearance. Infants may be assuming the frog leg position.⁶⁵ In cases of perforation, bluish discoloration of the scrotum may be noticed.⁶⁵

Differential diagnosis includes sepsis, intestinal atresia, malrotation/volvulus, inguinal hernia, and pyloric stenosis.

NEC is a clinical diagnosis and generally uses the modified Bell’s criteria.⁶⁶ The criteria (see Table 3) classify NEC by systemic signs, intestinal signs, and radiologic signs.⁶⁷ There are six categories that correspond to the severity of illness and help guide treatment. In all cases of NEC, antibiotics are recommended with increasing duration based on severity.⁶⁷ Of the varying antibiotic regimens commonly used, one systematic review found no evidence to support specific recommendations on antibiotic choice or duration.⁶⁸ These regimens included ampicillin plus gentamycin with the addition of clindamycin, metronidazole, or enteral administration of gentamycin. In the most severe cases when perforation is present, surgical management is recommended.

NEC is an emergent inflammatory gastrointestinal disorder. Its presentation often can be nonspecific but can include feeding intolerance, bloody stools, signs of shock, and abdominal distention. Diagnosis is based on systemic signs, intestinal signs, and radiologic findings. Treatment is antibiotics and, in some severe cases, surgery.

Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a set of genetic disorders that lead to deficient steroid production. There are multiple disorders that affect varying steps along the steroidogenesis pathway, resulting in deficient/abnormal production of corticosteroids, mineralocorticoids, and sex steroids depending on which pathway enzyme is affected.⁶⁹

The inheritance of CAH is exclusively autosomal recessive. The pathophysiology, presentation, and management of each condition depends on where on the pathway these defective enzymes act.⁶⁹ An enzyme defect along the pathway leads to deficient/ineffective downstream products and potential excess of upstream products and/or disruption of feedback mechanisms. For example, a deficiency in 17-alpha hydroxylase results in the inability to produce cortisol or sex hormones and also leads to the overproduction of adrenocorticotropic hormone (ACTH).⁷⁰

CAH occurs in approximately one in 9,498 births, although other studies have found the overall incidence to be lower.⁷¹ The incidence appears to vary by ethnic group, with the lowest rates in African Americans.⁷² The most common mutation causing CAH is a 21-hydroxylase deficiency followed by 11b-hydroxylase deficiency and 17-hydroxylase deficiency.⁷³ Given that these are the predominant mutations, they will be the focus of this article. Overall mortality for those with CAH is three times what would be expected in those without the disorder.⁷⁴

The adrenal glands, which are composed of the adrenal cortex and adrenal medulla, function to produce various hormones. The adrenal medulla is responsible for secreting catecholamines, and the adrenal cortex is responsible for producing aldosterone, cortisol, and sex hormones. In cases of CAH, there is a deficient enzyme along the steroid synthesis pathway. There are two forms of CAH: classic and non-classic. In classic CAH, there is little to no enzyme function, whereas in non-classic, there is limited enzyme function. Classic CAH is the more severe form and is either detected at birth or presents early in cases without testing, whereas non-classic may present with more subtle symptoms later in life. The focus of this section will be classic CAH because this is more relevant to the emergency physician.

21-hydroxylase deficiency: Deficiency in 21-hydroxylase prevents the production of aldosterone and cortisol and can lead to excess sex steroid production due to buildup of cortisol precursors.⁷⁵

11b-hydroxylase deficiency: Deficiency in 11b-hydroxylase prevents the production of cortisol the leads to overproduction of precursor molecules and androgen excess.⁷⁶

17-hydroxylase deficiency: Deficiency in 17-hydroxylase prevents the production of cortisol and sex hormones while resulting in excess aldosterone.

Clinical presentation is varied based on the specific enzyme deficiency. Infants generally are screened for 21-hydroxylase deficiency at birth since it is the most common form of CAH, but these results take five to seven days to come back, and this testing can be missed in the setting of home births or births that occur at birthing centers.⁷⁷

In cases of 21-hydroxylase deficiency, symptoms of salt wasting may be present in severe cases. This can manifest within the first five days of life as dehydration, failure to thrive, and shock. Additionally, patients may present with symptoms of androgen excess, which is most obviously seen in females as ambiguous genitalia but may be less obvious in males.⁷⁷ Initial laboratory evaluation may be significant for hyponatremia, hyperkalemia, and alkalosis. Definitive diagnosis is based on measuring serum 17-hydroxyprogesterone. The laboratory evaluation also should include a steroid profile and ACTH level, ideally before steroids are given.

The differential diagnosis includes congenital heart disease, endocrine dysfunction, inborn errors of metabolism, disorders of sex development, feeding issues, and exogenous androgen exposure.

In cases where significant salt wasting is suspected, treatment in the emergency department should not be held until formal diagnosis is made. It often is difficult to distinguish CAH from other causes of shock. Given that corticosteroids are recommended in the setting of refractory shock outside of CAH and the difficulty of diagnosing CAH in the emergency department, early administration of corticosteroids is prudent.⁷⁸

In patients presenting in adrenal crisis with known CAH or where CAH is suspected, hydrocortisone at 50 mg/m², which in standard practice generally equates to about 25 mg, should be administered parenterally.⁷⁹ Patients may require more than one round of stress dose steroids. After clinical improvement with stress dosing is achieved, an additional 6.25 mg should be given each six hours for 24 hours. Stress dose glucocorticoids also are recommended in the setting of fever > 38.5°C, significant trauma, and gastroenteritis in the setting of known CAH.⁷⁹ Additionally, electrolyte abnormalities should be treated as appropriate.

CAH is a set of genetic conditions leading to defects in the steroidogenesis pathway. The most common disorder, 21-hydroxylase deficiency, can go undiagnosed at birth in non-traditional settings. It results in the deficient production of aldosterone and cortisol while also leading to the overproduction of sex steroid production. Patients presenting to the emergency department with features of severe salt wasting or those in adrenal crisis should be treated promptly with hydrocortisone.

Neonatal Sepsis

Neonatal sepsis is a systemic infection caused by viral, bacterial, or fungal microorganisms. Given the neonate’s poorly developed immune system, these infections pose significant risk of death and permanent injury. The infections are either acquired directly from the infant’s mother or through environmental exposure. Neonatal sepsis generally is divided into early (within 72 hours of birth) and late (occurring after 72 hours of birth).

The incidence of hospitalization for neonatal sepsis is estimated to be 30.8 to 49.5 cases per 1,000 births in all infants and 85.4 cases per 1,000 births in preterm infants.^80,81 Some studies cite significantly lower incidence, and the variability in reported incidence likely is due to the unclear definition of neonatal sepsis.⁸² Deaths attributed to neonatal sepsis are estimated at 0.74 deaths per 1,000 births.⁸¹ Since 1990, the incidence of neonatal sepsis has declined 11.38% and deaths have declined 27.35%.⁸¹

It generally is thought that early neonatal sepsis is vertically acquired through the mother and late neonatal sepsis is horizontally acquired through a neonate’s environment, although this is not universally true.⁸² The most common pathogens implicated in vertical transmission include Group B Streptococcus (GBS), Escherichia coli, coagulase-negative staphylococci (CONS), Haemophilus influenzae, and Listeria monocytogenes, whereas Staphylococcus aureus and other gram-negative bacteria are most commonly implicated in horizontal transmission.⁸³

Risk factors associated with neonatal sepsis include prematurity, premature rupture of membranes, maternal infections, advanced maternal age, low birth weight, increased length of hospital stay, and NICU interventions.⁸⁴

Findings of early neonatal sepsis may be subtle and therefore missed. Presentation can be nonspecific with irritability and poor feeding. On physical exam, temperature abnormalities (fever or hypothermia), heart rate abnormalities (tachycardia or bradycardia), respiratory distress, neurologic abnormalities (such as lethargy, seizures, and decreased responsiveness), and abdominal distension may be present.^83,85

In neonates who are febrile but not obviously septic, the American Academy of Pediatrics has created a useful pathway (see Figure 1 in this article: https://publications.aap.org/pediatrics/article/148/2/e2021052228/179783/Clinical-Practice-Guideline-Evaluation-and), which helps guide workup and treatment. These recommendations suggest obtaining a broad workup, including urine analysis, blood cultures, and cerebrospinal fluid (CSF) analysis, before starting antimicrobial treatment with or without acyclovir dependent on herpes simplex virus (HSV) risk, followed by a period of observation in the hospital at a minimum of 24-36 hours if culture data are negative, and a longer period of treatment/observation dependent on culture results.⁸⁶

Diagnosis of neonatal sepsis in the emergency department is clinical. The gold standard of diagnosis, a positive blood culture, is limited by the length of time to achieve results. In cases of neonatal sepsis, treatment should be started prior to the return of blood culture data. Other cultures, such as urine and CSF, should be obtained, but these also are similarly limited. Other laboratory data, including urinalysis and complete blood counts with differential, can be considered but should not be relied on for the diagnosis of neonatal sepsis.^83,85

Antibiotics should be started in those with a suspicion for neonatal sepsis before confirmatory testing returns. The Neonatal Early-Onset Sepsis Calculator developed by Kaiser Permanente can be an effective tool in risk stratifying for the need of antibiotics (https://neonatalsepsiscalculator.kaiserpermanente.org/).⁸⁷

Empiric antibiotic regimens generally include β-lactam aminopenicillin and an aminoglycoside.^83,85 This can be broadened with the addition of vancomycin to cover staphylococcal species in the setting of late onset neonatal sepsis (> 72 hours).⁸⁵ If there is a suspicion for meningitis, a third-generation cephalosporin likely will provide adequate coverage of causative organisms. In cases of suspected HSV infection, acyclovir should be added.⁸³ Patients with suspected neonatal sepsis should be admitted to the hospital for further observation and management.

Neonatal sepsis is a systemic infection due to viral, fungal, or bacterial organisms. The presentation is vague but can include cardiac, respiratory, and neurologic abnormalities. Early recognition and treatment are important for best outcomes.

Neonatal Hypoglycemia

Neonatal hypoglycemia is a common, often transient, hypoglycemia found as neonates transition from a maternal glucose supply to meeting their own metabolic needs. These episodes normally are short-lived and resolve with regular feedings. In some instances, such as in underlying metabolic derangements, prolonged intervention is required. Generally it is thought that 47 mg/dL (2.6 mmol/L) is the threshold defining neonatal hypoglycemia, although this is not universally agreed upon.⁸⁸ If not adequately treated, these neonates may be at risk of seizure or other neurologic and metabolic disturbances.

Neonatal hypoglycemia occurs in approximately 5% to 15% of all births, but it can occur in as a high as 50% of births in which the neonates have risk factors.⁸⁸ Neonatal hypoglycemia has been associated with neurodevelopmental abnormalities in young children, but the data are mixed.⁸⁸

The pathophysiology of neonatal hypoglycemia is related to infants’ inability to independently procure nutrition, poor glycogen stores, and immature regulatory systems.⁸⁹ Conditions that lead to hyperinsulinism, growth hormone deficiency, cortisol deficiency, and inborn errors of metabolism put neonates at significantly increased risk.⁹⁰

Observation generally is recommended for infants up to 48 hours in high-risk categories, since glucose homeostasis generally can be achieved by then except in cases of metabolic abnormality. Typically, neonates spend this period in the hospital, but in cases of non-hospital birth, these patients may present to the emergency department. Clinical presentation of hypoglycemia can be nonspecific, such as seizures, lethargy, and poor feeding.⁸⁹ In some cases of hypoglycemia, neonates may display no outward signs.

Testing is with glucose monitoring. It is important to note that at low blood glucose levels, the point-of-care glucometers have wide variability and generally are less accurate. Typically, a blood glucose level of greater than 47 mg/dL pre-feeding is considered normal, although if a neonate has evidence of altered mental status or is post-feeding, the threshold would be elevated.

Treatment is focused on elevating blood glucose. In symptomatic neonates with a blood glucose of < 40 mg/dL, IV dextrose-containing fluids should be administered.⁹⁰ In asymptomatic patients with a glucose greater than 25 mg/dL, feeding may be attempted, but rates lower than 25 mg/dL warrant IV dextrose.

Neonates with transitional hypoglycemia generally will be able to achieve glucose homeostasis within 48 hours. If hypoglycemia persists, there likely is a pathologic cause of the hypoglycemia. IV dextrose-containing fluid should be bolused at 200 mg/kg, followed by an infusion of around 4 mg/kg to 8 mg/kg per minute.⁸⁸ It also is recommended to supplement feeds with an oral dextrose gel at 200 mg/kg.⁸⁸

Neonates with transient hypoglycemia should be observed in the inpatient setting until at least 48 hours after birth with resolution of the hypoglycemia or until a pathologic cause of the hypoglycemia is identified and adequately addressed.

In summary, neonatal hypoglycemia generally is a transient period where neonates are susceptible to hypoglycemia due to their unique metabolic circumstances. It typically resolves within 48 hours after birth unless there is a pathologic cause. It is treated with routine feeding of IV dextrose-containing fluids if severe. These neonates should be observed in the inpatient setting until their hypoglycemia resolves.

Neonatal Hyperbilirubinemia

Neonatal hyperbilirubinemia occurs in the majority of neonates but often is benign and self-limited. In cases of severe hyperbilirubinemia, devastating neurologic injury or even death may occur. Kernicterus is the chronic form of hyperbilirubinemia encephalopathy that often is associated with devastating neurologic outcomes.

Neonatal hyperbilirubinemia occurs in 60% to 80% of all births, with 10% developing clinically significant hyperbilirubinemia.⁹¹ Hyperbilirubinemia encephalopathy occurs in approximately 12.6/100,000 births.⁹² Kernicterus, a chronic form of hyperbilirubinemia encephalopathy, has a mortality rate of 10% and a morbidity rate of 70%.⁹³

Risk factors of neonatal hyperbilirubinemia include ABO incompatibility, G6PD deficiency, exclusive breastfeeding, and premature birth.⁹⁴

Neonates have a higher turnover of red cells, resulting in increased production of bilirubin. Additionally, they are less able to excrete unconjugated bilirubin and less able to conjugate bilirubin, which is more easily excreted.⁹⁵ These factors combined lead to increased unconjugated bilirubin levels in neonates. Bilirubin is yellow; therefore, when it builds up in the blood supply, a neonate’s skin may appear yellowed or jaundiced. When bilirubin levels reach extremely high levels, they deposit in the central nervous system (CNS) tissue, causing sometimes irreversible CNS damage.

Clinical features include the development of jaundice. Jaundice occurring within the first 24 hours of life should raise suspicion for a hemolytic cause of hyperbilirubinemia. Depending on how severe the hyperbilirubinemia is, nonspecific signs of encephalopathy, including lethargy, poor feeding, vomiting, and seizures, may be present.⁹⁶

Diagnosis is based on the total serum bilirubin value. Treatment thresholds are based on gestational age, risk factors, and actual age of the neonate. Treatment, which typically is completed in the inpatient setting, includes phototherapy for the less severe cases and exchange transfusion therapy in the most severe cases.

Given the complexity and multiple factors that need to be taken into consideration, we recommend physician reference the Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation created by the American Academy of Pediatrics (https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of) when initiating treatment or deciding who should be admitted to initiate treatment.⁹⁷

All patients with neonatal hyperbilirubinemia requiring treatment should be admitted to the hospital.

Neonatal hyperbilirubinemia is a common condition affecting most newborns, although it generally is benign. In severe cases, which are significantly less common, it can lead to serious neurological injury or death. Risk factors include ABO incompatibility, G6PD deficiency, breastfeeding, and prematurity. Diagnosis is based on serum bilirubin levels, and treatment ranges from phototherapy to exchange transfusion, depending on severity.

Summary

Neonates may present to the emergency department during the first week of life with vague and nonspecific symptoms due to serious and life-threatening conditions. Awareness of these disorders is the first step in their detection.

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