Neonatal Gestational Age and Birth Weight
As a prerequisite to determine whether neonates fall into reference ranges, all infants are classified on the basis of gestational age (GA) and birth weight (BW).
Early ultrasonography improved the accuracy of pregnancy dating, but discrepancies in dates, physical examination findings, and size necessitate further evaluation. If prenatal care has been lacking, physical assessment remains the primary clinical determinant of GA. GA is noted in completed weeks after the onset of the last menstrual period (LMP).
A term infant is an infant who is born after 37 completed weeks (ie, ≥37 0/7 weeks’ gestation). A preterm infant is born before 37 completed weeks (ie, <37 weeks’ gestation). A postterm infant is born after 42 0/7 weeks’ gestation.
Several terms are used to classify neonates according to BW, as follows:
Low birth weight (LBW) neonates weigh less than 2500 g, either because of prematurity, because they are small for their gestational age, or both
Very low birth weight (VLBW) neonates weigh less than 1500 g (3 lb 5 oz) at birth 
Extremely low birth weight (ELBW) neonates weigh less than 1000 g (2 lb 3 oz) at birth
These classifications aid the clinician in predicting clinical courses and outcomes.
Small for gestational age (SGA) neonates are those whose BW is less than the 10th percentile for their gestational age. These infants are more prone to hypoxemia and meconium aspiration during labor. They are also at higher risk for polycythemia and require special attention to prevent hypothermia and hypoglycemia. The placenta should be carefully examined by pathologists. These infants are at increased risk for developing necrotizing enterocolitis (NEC). They often have higher than normal caloric requirements for growth.
Intrauterine growth retardation or restriction (IUGR) is used to describe neonates whose growth is not at the 10th percentile for their gestational age in utero or in neonates in whom the weight percentile is decreasing in relation to GA (ie, crossing the 10th percentile lines); these neonates may be SGA.
Considerable evidence has shown that IUGR and smallness for gestational age can increase the risk of non–insulin-dependent diabetes mellitus (NIDDM), coronary heart disease, hypertension, and stroke. This has led to a rapidly growing field: study of the fetal origins of adult diseases.
Large for gestational age (LGA) infants are those whose weight is greater than 90th percentile for their gestational age. These infants are at increased risk for perinatal asphyxia, birth injury, hypoglycemia, hypocalcemia, polycythemia, and thrombocytopenia. Infants of mothers with diabetes are often large for gestational age.
Neonatal Fluid and Electrolyte Management
Over the first 5-7 days following birth, term infant body weight (BW) decreases by 3-7%; after that, healthy term infants should gain 10-20 g/kg/day. Expect preterm infants to lose 5-15% of BW during transition, and they may not regain the lost BW until they are aged 10-15 days. After that, preterm infants should gain 15-25 g/kg/day. In terms of head circumference and length, the authors use goals of an increase of 0.5-1 cm/week and an increase of 1 cm/week, respectively.
Estimates suggest that preterm infants in a thermoneutral environment require approximately 40-60 kcal/kg/day for the maintenance of BW, on the assumption that adequate protein is provided.
Additional calories are needed for growth, with the smallest neonates tending to demonstrate the greatest need, in that their growth rate is highest.
For adequate growth, term infants require 110-120 kcal/kg/day. Preterm infants require as much as 150 kcal/kg/day. For infants to achieve optimal weight gain, maintain a thermoneutral environment.
Total fluid intake
The initial step in nutritional support is to determine an infant's fluid requirement, which depends on gestational age, postnatal age, and any underlying disease.
Premature infants have increased fluid requirements because of their increased surface area and the immaturity of their skin. Premature infants may require as much as 200 mL/kg/day, though with the current techniques used to minimize fluid losses (eg, immediate placement into a humidified isolette), requirements in excess of 150 mL/kg/day are now less common.
In the case of a patent ductus arteriosus (PDA), fluid restriction (100-120 mL/kg/day) is considered part of medical management.
In bronchopulmonary dysplasia (BPD), fluid restriction to avoid pulmonary edema should be balanced by the fact that these infants require good (and often higher than normal) caloric intake. This intake facilitates lung healing and development, as well as overall growth. The energy required for increased work of breathing also requires additional calories.
Parenteral nutrition is crucial for many sick and preterm infants in whom full enteral feeding cannot be attained quickly. Current pharmacy support allows total parental nutrition (TPN) to be initiated on the day of admission to the neonatal intensive care unit (NICU).
The caloric value of dextrose is 3.4 kcal/g. Term neonates require approximately 3-5 mg/kg/min of intravenous (IV) dextrose to maintain euglycemia (ie, blood glucose level of 40-100 mg/dL). Preterm neonates usually require higher infusion rates of dextrose (~5-6 mg/kg/min IV), in that they have a higher brain-to-BW ratio and higher total energy needs. The dextrose infusion rate (in mg/kg/min) can be calculated with the following formula:
Infusion rate = [dextrose concentration (%) × dosage (mL/kg/day)]/144
For example, if 80 mL/kg/day of 10% dextrose in water (D10W) is required, the infusion rate is determined as follows:
(10 × 80)/144 = 800/144 = 5.5 mg/kg/min
Hypoglycemia is defined as a serum blood glucose level lower than 40 mg/dL in the term or preterm infant. Neonates with a low serum glucose level benefit from early introduction of milk feeding, when appropriate. Those who are symptomatic, are unable to feed, or have a glucose level lower than 25 mg/dL should be treated with 200 mg/kg of glucose (2 mL/kg of D10W) over 1 minute, followed by appropriate IV fluid maintenance. Prompt treatment is necessary to prevent both immediate and long-term consequences, such as seizures or brain injury.
The caloric value of amino acids is 4 kcal/g. It has been demonstrated that infants who do not receive amino acids in the first day of life catabolize body protein at a rate of at least 1 g/kg/day. Multiple studies have demonstrated the safety and benefits of supplementing up to 2.4 g/kg/day of amino acids beginning in the first 24 hours. This is increased until a goal of 3-4 g/kg/day is met.
The caloric value of 20% lipid emulsion is 2 kcal/mL or 9 kcal/g. Current data suggest that preterm infants are at risk for essential fatty acid (EFA) deficiency within 72 hours of life if an exogenous fat source is not delivered. This deficiency state can be avoided through administration of 0.5-1 g/kg/day of lipid emulsion in the first 24 hours, advanced as tolerated in 1 g/kg/day increments to a target dosage of 3 g/kg/day.
Sodium (Na) requirements are generally 2-3 mEq/kg/day in the term neonate. Premature infants require 3-5 mEq/kg/day of sodium, and they may require even more if renal losses are high.
In postoperative patients who have ostomies, sodium losses may be greater. Replacing ostomy sodium losses and maintaining sodium balance is important.
Neonates with total body sodium depletion are at increased risk of failure to thrive. Urine sodium level provides a good indication of total body stores. Serum sodium levels may be within the reference range in conditions of sodium depletion. A urine sodium level lower than 10 mEq/L in an infant with an ostomy suggests the need for sodium supplementation.
Potassium (K) requirements are generally in the range of 1-2.5 mEq/kg/day. Potassium should not be supplemented if urine output is poor. Extra potassium supplementation may be required when diuretic therapy is used in infants with bronchopulmonary dysplasia.
Increasing the proportion of anions provided as acetate aids in the treatment of metabolic acidosis. Many infants on diuretic medications frequently need more chloride supplementation, especially in the form of potassium chloride (KCl).
Calcium (Ca) and phosphorus (P) supplementation are essential for normal bone formation. Current TPN solutions can provide up to 60 mg/dL (15 mmol/L) of calcium and 46.5 mg/dL (15 mmol/L) of phosphorus. Despite the good retention of calcium (88-94%) and phosphorus (83-97%), only 50-60% of the in-utero accretion of calcium and phosphorus can be attained with TPN. Therefore, preterm infants receiving prolonged TPN are at increased risk for osteopenia, which can be exacerbated by cholestasis, steroid therapy, and loop diuretics.
The structural and functional integrity of the gastrointestinal (GI) tract depends on the provision of enteral feeding. Withholding enteral feeding increases the risk for mucosal thinning, flattening of the villi, and bacterial translocation.
Human milk provides the criterion standard for feeding term infants. Fortified human milk could be considered the optimal diet in preterm infants.
Preterm infant formulas differ from those for term infants in several ways that benefit the growing premature infant. Preterm formulas have higher levels of protein and minerals than term formulas do. They contain more calcium and phosphorus, which increase net mineral retention and improve bone mineral content (BMC). The fat blends in preterm formulas include a portion of the fat as medium-chain triglycerides (MCTs).
Formula-fed preterm infants born weighing less than 1800-2000 g should be discharged with preterm discharge formulas (eg, EnfaCare or NeoSure) that contain 22 kcal/oz and have higher calcium and phosphorus concentrations. With these formulas, the growing preterm infant has a nutrient intake between that of preterm and term infant formulas. Using preterm discharge formulas until a postnatal age of 9 months results in greater linear growth, weight gain, and BMC than is seen with low birth weight (LBW) infants who are fed term formula.
Protein hydrolysate formulas (eg, Pregestimil, Nutramigen, Neocate), in which protein is extensively hydrolyzed, are occasionally needed in infants with significant malabsorption due to GI or hepatobiliary disease, including short-gut syndrome, biliary atresia, cholestasis, cystic fibrosis, and protracted diarrhea. Check with the neonatal dietitian for availability of special formulas.
Short-bowel syndrome is a complication of necrotizing enterocolitis or congenital bowel anomalies when an operation has been performed in which a significant amount of small intestine has been removed. Some of these infants have significant malabsorption, the extent of which depends on the amount of bowel removed and on the part of the bowel removed. Although controversial, the presence of the ileocecal valve after resection may be significant, because it can act as a barrier to bacterial flowing from the colon to the small intestine, and it is important in regulating the exit of fluid and nutrients from the small intestine.
Malabsorption arises from a reduced surface area for nutrient absorption and depends on the characteristics of the bowel that was resected. For example, the jejunum is important for absorbing nutrients, whereas the ileum is responsible for absorbing fluid, electrolytes, bile salts, and vitamin B12. Therefore, resection of the ileum results in more dramatic deficiencies than those seen with resection of the jejunum. Mucosal hyperplasia and adaptation of the remaining bowel begins 24-48 hours after resection. However, this adaptation does not occur in the absence of enteral nutrition. Therefore, as soon as the ileus resolves, initiate continuous enteral nutrition.
Because TPN is critical for providing nutrition while feedings are slowly advanced, institute it immediately after surgery. Cycling TPN to provide a period of several hours without TPN may prevent cholestasis. Food refusal is a common problem in infants with short-bowel syndrome and prolonged TPN. To avoid this, give small bolus feedings three or four times daily when feeding is initiated, and introduce solid food in a timely manner.
Although enteral feedings are critical to gut healing after surgery, they may exacerbate malabsorption if they are continued despite dumping. Feedings should not be advanced if stool output is greater than 40-50 mL/kg/day, if the stool is strongly positive for reducing substances, if stool pH is lower than 5.5, or if stool volume increases by more than 50%. Advancing the feedings at this time can cause mucosal injury and osmotic diarrhea.
The most common terminal event in infants with short-bowel syndrome is liver failure caused by prolonged TPN. This may be minimized with early enteral feedings, prevention of sepsis whenever possible, cycling of TPN, and, possibly, mucous fistula refeeding. Phenobarbital is not particularly useful. In a study by Teitelbaum et al, cholecystokinin-octapeptide (CCK-OP) failed to significantly reduce the incidence of parenteral nutrition–associated cholestasis (PNAC) or reduce levels of conjugated bilirubin (CB). 
Ursodeoxycholic acid (UDCA) is frequently used to decrease direct hyperbilirubinemia, but it can be administered only enterally; therefore, there are limitations in infants receiving only TPN. A study by Arslanoglu et al reported that a progressive increase in the dose of UDCA with a small dose in infants on nothing-by-mouth (nil per os; NPO) status did not result in side effects.  A few retrospective studies suggested that UDCA can improve the course of PNAC in newborn infants. 
Neonatal Ventilatory Management
Continuous positive airway pressure
The goal of continuous positive airway pressure (CPAP) is to prevent alveolar collapse at end expiration. It also allows supplemental oxygen to be delivered continuously. Distending pressure is usually applied via either nasal prongs or mask.
CPAP is used in infants with moderate respiratory distress and recurrent apnea. It helps weaning from mechanical ventilation.
Even in extremely preterm infants, a developing trend is to start nasal CPAP immediately after birth, and intubation is used only when necessary.
Conventional mechanical ventilation
Conventional mechanical ventilation is the most commonly used mode of ventilation in most neonates. Optimal management can be achieved by using modes that allow synchronization with the neonate's own breathing.
The initial settings for ventilating a neonate depend on the underlying disease, the severity of the disease process, and the size of the neonate. The ventilator rate is adjusted on the basis of measures partial pressure of carbon dioxide (PCO2). The reference range for PCO2 is 35-45 mm Hg.
A normal range of PCO2 is desirable when the risk of intraventricular hemorrhage is greatest. Thereafter, a management strategy of permissive hypercapnia, in which the PCO2 is allowed to increase modestly (eg, to 45-55 mm Hg), could be of benefit. This strategy is used to decrease lung barotrauma, volutrauma, or both. In addition, low PCO2 levels have been linked to poor neurodevelopmental outcomes in neonates and thus should be avoided.
Peak pressures or volumes, depending on whether a pressure or hybrid mode is chosen, are adjusted to achieve good chest movement. A hybrid mode is one in which a tidal volume is targeted but a characteristic pressure mode of ventilation is used.
For all conventional ventilation modes, a tidal volume monitor can be used to assess the adequacy of the pressures or volume chosen; a tidal volume of 4-6 mL/kg is recommended. Higher volumes may result in barotrauma, volutrauma, or both, whereas lower values may result in atelectasis. The positive end-expiratory pressure (PEEP) can initially be set at 4 cm H2O; however, this can vary according to the infant and the disease process and frequently must be higher, especially in the presence of significant parenchymal disease.
High-frequency ventilation (HFV) delivers lower tidal volumes that are less than the anatomic dead space at rapid rates. Three types are used: high-frequency jet ventilators (HFJVs) and high-frequency flow interrupters (HIFIs), in which exhalation is passive, and high-frequency oscillatory ventilators (HFOVs), in which exhalation is active. HFV can reduce barotrauma at lower volumes and optimize lung volume at higher volumes.
HFV is useful in symmetric lung disease (eg, respiratory distress syndrome [RDS], pneumonia) and allows the use of optimal lung volumes when conventional mechanical ventilation is unsuccessful. HFV is also useful in air-leak syndromes (eg, pneumothorax, pulmonary interstitial edema), pulmonary hypoplasia (including congenital diaphragmatic hernia), and nonhomogeneous lung disease (eg, meconium aspiration syndrome). HFV reduces barotrauma and prevents further injury to the lungs.
Postoperative ventilatory management
Infants are often sedated postoperatively, requiring an increased ventilator rate to prevent underventilation and hypercarbia until they are more awake and breathing more frequently and effectively. Alternatively, especially in infants who have no lung disease, postoperative ventilation can cause low PCO2 levels and overventilation. For both reasons, blood gas analysis should be considered shortly after surgical procedures in patients in the NICU.
Infants undergoing abdominal surgery may require increased PEEP to counteract the pulmonary effects of increased abdominal pressure after surgery. HFOV seems to be an effective rescue measure for infants with respiratory failure secondary to increased intra-abdominal pressure. In a study by Fok et al, the oxygenation status of all infants significantly improved within an hour of changing from conventional mechanical ventilation to HFOV. Infants who were hypercapnic on conventional ventilation also showed a reduction in arterial PCO2. 
Neonatal Medical Diseases
Respiratory distress syndrome
Respiratory distress syndrome (RDS) is a disease in premature infants that is characterized by surfactant deficiency. Surfactant is produced by type II alveolar cells in the lungs, and it is produced in increasing quantities after 32 weeks' gestation. The incidence of RDS in neonates born before 30 weeks' gestation who are treated with antenatal corticosteroids is approximately 35%. Without antenatal corticosteroids, the incidence increases to 60%. The incidence is 10% in those born at 30-34 weeks' gestation (25% if they are not treated with antenatal corticosteroids) and 5% in those born at more than 34 weeks' gestation.
The natural history of RDS is that it develops in neonates during their first few hours of life, worsens over 48-72 hours, and then improves. The clinical course is changed with exogenous surfactant treatment.  Exogenous surfactant is effective in treating RDS, and it can be used for prophylaxis in the delivery room in high-risk neonates (ie, those at <28 weeks' gestation) or as a rescue treatment when symptoms develop. Understanding the clinical course is important so that premature infants are not transferred for nonemergency surgical treatment of congenital anomalies until their respiratory status stabilizes.
Bronchopulmonary dysplasia (BPD) is relatively common in premature neonates. It is characterized by an arrest in alveolar growth in premature infants, requiring respiratory support. It is generally defined as abnormal chest radiographic findings and an oxygen requirement at day 28 (old definition) or 36 weeks' postconceptional age (new definition). Lower gestational age (GA) and birth weight (BW), acute lung injury at birth, and higher ventilator and oxygen settings are major contributors to the development of BPD. Persistence of inflammation and additional insults such as a significant infection or necrotizing enterocolitis are often additional risk factors.
Therapies used include theophylline, diuretics, and inhaled bronchodilators. Approaches under development include surfactant treatment of initial RDS, aggressive extubation, and various mechanical ventilator strategies. In the past, postnatal steroids were used because of their remarkable effect on pulmonary parameters; however, with increasing concerns about the effect of steroids on brain development and long-term neurologic outcome, these are now used less frequently. Stem cell therapy has shown promise in lung regeneration and as a treatment for BPD. 
BPD is an independent risk factor for poor neurodevelopmental outcome.
Patent ductus arteriosus
Patent ductus arteriosus (PDA) arises when the ductus arteriosus does not close in the neonate's first few days of life or when it reopens after functional closure, usually within the first 6 weeks of life. Studies have suggested that a developmental absence of the oxygen sensitivity of L-type calcium channels in preterm ductus arteriosus smooth-muscle cells impairs oxygen constriction, contributing to PDA. 
The incidence of PDA is as high as 60% in infants weighing less than 1500 g, with an even higher incidence in the smallest infants. Symptoms of a PDA are a result of left-to-right shunting of blood once the pulmonary vascular resistance decreases; this causes pulmonary edema with concomitant respiratory problems.
In severe cases, PDA can also be associated with pulmonary hemorrhage. It may also contribute to the development of BPD. Initial treatment of symptomatic PDA involves fluid restriction, increased positive end-expiratory pressure (PEEP) if the patient is receiving respiratory support, and administration of indomethacin or ibuprofen.
If an initial course of indomethacin or ibuprofen does not close the PDA, a repeat course can be used. If repeated courses of indomethacin are unsuccessful or if indomethacin or ibuprofen use is contraindicated (renal disease, acute bleeding, necrotizing enterocolitis), the PDA must be surgically ligated if it is believed to be hemodynamically significant.
Persistent pulmonary hypertension of newborn
Persistent pulmonary hypertension of the newborn (PPHN) is a condition in neonates caused by the failure of pulmonary vascular resistance to decrease after birth. It leads to pulmonary hypertension and right-to-left shunting of blood from the right side of the heart through the patent foramen ovale, ductus arteriosus, or both. The lungs are bypassed, resulting in hypoxemia.
Strategies to maximize pulmonary blood flow include maintaining adequate oxygenation and systemic blood pressure and minimizing systemic acidosis. Often, a minimal stimulation protocol is advantageous. Implementing respiratory alkalosis for PPHN is no longer recommended, because it may have deleterious neurologic, otologic, and long-term pulmonary effects. Nitric oxide, high-frequency ventilation (HFV), and surfactant treatment in term infants are effective in some cases. These therapies have dramatically decreased the number of patients requiring extracorporeal membrane oxygenation (ECMO). For infants who do not respond to these measures, ECMO can be life-saving.
Neonatal sepsis is a major source of morbidity and mortality in the neonate. In addition to common bacterial infections, neonates are at increased risk for opportunistic infections, including those caused by candidal species, herpes simplex virus (HSV), and cytomegalovirus (CMV), because of the immaturity of their immune response. Premature infants are at even greater risk.
Infants may manifest an infection in subtle ways. They may have temperature instability but often do not have a fever; fever is more common in viral sepsis. Frequently, sepsis may present as increasing apnea and bradycardic episodes. A total white blood cell (WBC) count lower than 5000/µL, an absolute neutrophil count (ANC) lower than 1000/µL, and an immature-to-total neutrophil (I:T) ratio greater than 0.2 have all been correlated with the presence of bacterial infection. An elevated WBC count higher than 20,000/µL is not predictive in newborns. If an infant is receiving steroids, symptoms of infection may be masked.
The early-onset sepsis (EOS) rate is 1 to 4 cases per 1000 live births. Data from the Center for Disease Control (CDC) showed that the incidence of group B beta-hemolytic streptococcal (GBS) EOS decreased with the implementation of recommendations for intrapartum antibiotic prophylaxis (IAP) against GBS. However, the incidence of non-GBS EOS is unchanged among overall births; the incidence of non-GBS EOS is increasing among infants with very low birth weight (VLBW).
Late-onset sepsis (LOS) occurs after 3 days of life. Most instances of LOS occur in the neonatal intensive care unit (NICU) among infants with low birth weight (LBW). The National Institute of Child Health and Human Development (NICHD) neonatal research network found that from 1998 to 2000, 21% of their VLBW cohort had at least one episode of blood-culture–proven sepsis after age 3 days. Overall mortality was 17% in infected infants and 7% in uninfected infants.
Renal tubular acidosis
Renal tubular acidosis (RTA) is commonly observed in premature infants. In neonates, the threshold for bicarbonate reabsorption, which occurs mainly in the proximal tubule, is lower than that in adults; this threshold leads to physiologic plasma bicarbonate concentrations as low as 16-20 mmol/L in the premature infant and 19-21 mmol/L in the term infant. Infants have immature proximal tubules that impede the response to an acid load. However, the tubules mature postnatally, and renal bicarbonate wasting decreases as the neonate matures; this generally resolves by the time the neonate is aged 1 week.
As a consequence of this renal wasting of bicarbonate, infants may require supplemental acetate in their total parenteral nutrition (TPN) in the initial postnatal period. However, as the kidney matures, this higher amount of acetate can actually cause an increase in the baby's partial pressure of carbopn dioxide (PCO2) as a mechanism for normalizing pH. Thus, monitoring the base deficit or excess with blood gas levels is important to determine the relative amounts of acetate and chloride to provide in TPN.
Apnea of prematurity
Apnea of prematurity is a common problem in the NICU. Typically, neonates born before 34 weeks' gestation are at risk for this disease, in which the respiratory center is immature and healthy infants can become apneic. Standard treatments include the use of methylxanthines, such as caffeine and theophylline, and nasal continuous positive airway pressure (CPAP). Nasal noninvasive ventilation is currently being used. Antireflux medications are also used empirically in some infants with apneas, bradycardias, or both that may be related to gastroesophageal reflux (GER); however, few data exist to indicate that these episodes improve with the addition of antireflux medications.
When medicines are stopped, a period (eg, 1 week) of in-hospital observation without medication is important to monitor the infant for recurrence. Apnea of prematurity can appear as apnea, but it frequently manifests as bradycardia, with subclinical apnea or hypoventilation; occasionally, it occurs as desaturation episodes. Whether the treatment of anemia improves apnea, bradycardia, or both in preterm infants is controversial.
Intraventricular hemorrhage (IVH) is another disease related to prematurity. It is characterized by bleeding in the germinal matrix and periventricular regions of the brain. The incidence of IVH is 30-40% in infants who weigh less than 1500 g and 50-60% in infants who weigh less than 1000 g. Approximately 85% of IVHs occur in the first 72 hours of life; fewer than 5% occur in those older than 1 week.
Ultrasonography is used to classify the hemorrhage, as follows:
Grade I - Germinal matrix hemorrhage
Grade II - Germinal matrix hemorrhage with blood in the ventricle
Grade III - Germinal matrix hemorrhage with enough blood in the ventricle to distend it at the time of the IVH
Grade IV - Germinal matrix hemorrhage with extension into the brain parenchyma
Studies showed that extremely low birth weight (ELBW) infants, even with grades I-II IVH, have poorer neurodevelopmental outcomes at 20 months' corrected age than infants with normal cranial ultrasonographic findings. However, the studies found no significant difference in babies at more than 29 weeks’ gestation. 
Infants who have grade III IVH with increasing ventricular size post IVH and those who have grade IV IVH have a higher incidence of motor or intellectual impairment. Infants with grade III or IV IVH are at increased risk for posthemorrhagic hydrocephalus; some of these patients require ventriculoperitoneal shunts. Indomethacin is used for prophylaxis in some institutions  ; it has been shown to decrease the rate of grade III and IV IVHs.
Retinopathy of prematurity
Retinopathy of prematurity (ROP) is another disease of prematurity that affects neonates born at 31 weeks' gestation or earlier or those who weigh 1250 g or less at birth. It is a proliferative vascular vitreoretinopathy that can progress to fibrotic retinal scarring and detachment in some patients. If severe, it can cause significant visual problems, including blindness.
ROP is classified in terms of stages and zones according to the severity of the disease and its location, respectively. The staging of ROP is as follows:
Stage 1 - Cessation of vascularization that causes a white demarcation line between vascularized and nonvascularized parts of the retina
Stage 2 - Ridge of fibrovascular tissue projecting up from the retina
Stage 3 - Capillary proliferation (neovascularization) posterior to the ridge or extending into the vitreous
Stage 4 - Partial detachment caused by effusion or traction
Stage 5 - Complete retinal detachment
Retinal detachment results from contraction of the ridge scar tissue.
Plus disease denotes vascular engorgement and tortuosity of vessels in the posterior pole. In the past, the indication for surgery (cryotherapy or laser surgery) was attainment of threshold disease (ie, the presence of 5 consecutive or 8 total clock-hours of stage 3 disease with plus disease in zone 1 [posterior pole] or zone 2 [extending from zone 1 to the equator of the globe]). However, subsequent studies suggested that earlier surgical treatment in some patients with prethreshold disease may be advantageous.
Mintz-Hittner and Kuffel used intravitreal injection of bevacizumab in treating stage 3 ROP in zone I and posterior zone II. They reported that it was safe and effective in their small series of patients.  Kusaka et al, in a pilot study, suggested that intravitreal injection of bevacizumab seems to be associated with reduced neovascularization without apparent ocular or systemic adverse effects and thus may be beneficial for treating severe ROP that is refractory to conventional laser therapy. 
Delivery Room Management of Specific Neonatal Surgical Conditions
Congenital diaphragmatic hernia
In congenital diaphragmatic hernia (CDH), to decrease air entry into the bowel that occupies the chest cavity, bag-mask ventilation should be avoided, and immediate intubation is recommended. An orogastric Replogle tube should also be placed in the delivery room and attached to low suction to prevent gaseous distention of the stomach and intestine. These neonates may have surfactant deficiency; accordingly, surfactant is administered at a dose of 50% of the usual dose (because these infants have approximately half the usual lung volume for their body weight [BW]).
Infants with CDH often have persistent pulmonary hypertension and require intensive therapy, including high-frequency ventilation (HFV), inhaled nitric oxide, and, in some cases, extracorporeal membrance oxygenation (ECMO). Nitric oxide does not appear to be as effective in patients with CDH as it is in patients with persistent pulmonary hypertension of the newborn (PPHN) due to other etiologies.
Sildenafil, a phosphodiesterase-5 inhibitor, has been used in the treatment of pulmonary hypertension in adults and children. In a study by Noori et al, sildenafil improved cardiac output by reducing pulmonary hypertension refractory to inhaled nitric oxide in patients with CDH. 
In neonates with an abdominal-wall defect such as gastroschisis or a ruptured omphalocele, immediate attention in the delivery room is required to maintain normal body temperature. These neonates are at risk for hypothermia because a large intestinal surface area is exposed to the environment. A protective covering is placed while the neonate is in the delivery room; it usually consists of a moist gauze dressing and layers of cellophane. Alternatively, a sterile bag can be used. Orogastric decompression is also instituted. If the omphalocele is intact, it should be carefully protected.
Esophageal atresia may be the first condition recognized in the delivery room. The neonate may have copious secretions that can cause respiratory distress. Advancement of the orogastric tube is not possible. This tube should be left in place for suctioning to help prevent aspiration and to assist with radiographic confirmation of the diagnosis. Contrast material is not required to confirm the diagnosis; its use may result in aspiration.