Overview of short-term complications in preterm infants

INTRODUCTION — Complications of the preterm infant (gestational age <37 weeks) are divided into short-term complications that occur in the neonatal period, and long-term sequelae in patients who survive and are discharged from the neonatal intensive care unit (NICU).

This topic will provide an overview of the short-term complications that commonly occur in preterm infants. The long-term complications are discussed separately. (See "Overview of the long-term complications of preterm birth".)

Specific neonatal morbidities are discussed in detail in separate topic reviews:

●Anemia of prematurity (see "Anemia of prematurity (AOP)")

●Apnea of prematurity (see "Pathogenesis, clinical manifestations, and diagnosis of apnea of prematurity" and "Management of apnea of prematurity")

●Bacterial and fungal sepsis (see "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation" and "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation" and "Epidemiology and risk factors for Candida infection in neonates" and "Clinical manifestations and diagnosis of Candida infection in neonates" and "Treatment of Candida infection in neonates" and "Prevention of Candida infection in neonates")

●Bronchopulmonary dysplasia (BPD) (see "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis" and "Bronchopulmonary dysplasia (BPD): Management and outcome" and "Bronchopulmonary dysplasia (BPD): Prevention")

●Feeding difficulties (see "Neonatal oral feeding difficulties due to sucking and swallowing disorders" and "Breastfeeding the preterm infant" and "Growth management in preterm infants" and "Approach to enteral nutrition in the premature infant")

●Intraventricular hemorrhage (IVH) (see "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis" and "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and outcome")

●Low blood pressure and shock (see "Assessment and management of low blood pressure in extremely preterm infants" and "Neonatal shock: Etiology, clinical manifestations, and evaluation" and "Neonatal shock: Management")

●Metabolic abnormalities (hypoglycemia, hypocalcemia) (see "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia" and "Management and outcome of neonatal hypoglycemia" and "Neonatal hyperglycemia" and "Neonatal hypocalcemia")

●Necrotizing enterocolitis (NEC) (see "Neonatal necrotizing enterocolitis: Clinical features and diagnosis" and "Neonatal necrotizing enterocolitis: Management and prognosis" and "Neonatal necrotizing enterocolitis: Pathology and pathogenesis" and "Neonatal necrotizing enterocolitis: Prevention")

●Patent ductus arteriosus (PDA) (see "Patent ductus arteriosus (PDA) in preterm infants: Clinical features and diagnosis" and "Patent ductus arteriosus (PDA) in preterm infants: Management and outcome")

●Respiratory distress syndrome (RDS) (see "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis" and "Respiratory distress syndrome (RDS) in preterm infants: Management")

●Retinopathy of prematurity (ROP) (see "Retinopathy of prematurity (ROP): Risk factors, classification, and screening" and "Retinopathy of prematurity (ROP): Treatment and prognosis")

DEFINITIONS — Different degrees of prematurity are defined by gestational age (GA) or birth weight (BW) (table 1).

The classification based upon GA is as follows:

●Late preterm birth – GA 34 to <37 weeks

●Moderate preterm birth – GA 32 to <34 weeks

●Very preterm (VPT) birth – GA <32 weeks

●Extremely preterm (EPT) birth – GA <28 weeks

Preterm infants are also classified by BW:

●Low birth weight (LBW) – BW <2500 g

●Very low birth weight (VLBW) – BW <1500 g

●Extremely low birth weight (ELBW) – BW <1000 g

The above definitions are used throughout this review.

EPIDEMIOLOGY — The frequency and severity of neonatal complications among preterm infants increase with decreasing gestational age (GA) [1-3]. In a prospective population-based study conducted in France in 2011 (the EPIPAGE-2 study), the relative frequencies of severe neonatal morbidities according to GA category were as follows:

●Severe intraventricular hemorrhage (IVH; grades III and IV):

•GA 32 to 34 weeks – 0.6 percent

•GA 27 to 31 weeks – 4 percent

•GA 23 to 26 weeks – 13 percent

●Severe bronchopulmonary dysplasia (BPD):

•GA 32 to 34 weeks – No cases

•GA 27 to 31 weeks – 5 percent

•GA 23 to 26 weeks – 26 percent

●Severe retinopathy of prematurity (ROP):

•GA 32 to 34 weeks – No cases

•GA 27 to 31 weeks – 0.3 percent

•GA 23 to 26 weeks – 6 percent

●Severe necrotizing enterocolitis (NEC):

•GA 32 to 34 weeks – 1 percent

•GA 27 to 31 weeks – 3.5 percent

•GA 23 to 26 weeks – 5 percent

In the United States, Black and Hispanic preterm infants appear to have a greater risk of complications compared with White preterm infants. This was illustrated in a population-based cohort study of very preterm infants (GA <32 weeks) that found higher rates of BPD, NEC, IVH, and ROP among Black and Hispanic infants compared with White infants, even after adjusting for sociodemographic factors (eg, maternal age and education, insurance status) and maternal morbidities (eg, pregestational hypertension and diabetes, gestational diabetes, obesity) [4]. Asian American infants had comparable rates of BPD, NEC, and IVH to White infants but were at greater risk for ROP.

Additional details regarding the epidemiology of BPD, NEC, IVH, and ROP are provided separately:

●(See "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis", section on 'Epidemiology'.)

●(See "Neonatal necrotizing enterocolitis: Clinical features and diagnosis", section on 'Epidemiology'.)

●(See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Epidemiology'.)

●(See "Retinopathy of prematurity (ROP): Risk factors, classification, and screening", section on 'Incidence'.)

COMPLICATIONS — Preterm birth is a major contributing factor to infant mortality worldwide, particularly in high-income countries. In the United States, approximately two-thirds of all infant deaths occur among preterm infants (ie, <37 weeks gestational age [GA]) [5]. (See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality".)

Complications of prematurity are the underlying reasons for the higher rate of infant mortality and morbidity in preterm infants compared with full-term infants. The risk of complications increases with decreasing GA and birth weight (BW) [2,6]. Thus, infants born extremely preterm (EPT; GA <28 weeks) have the highest mortality rate (approximately 50 percent) and if they survive, are at the greatest risk for severe disability. (See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality", section on 'Risk factors for mortality'.)

Complications of the preterm infant are divided into short-term complications (eg, respiratory and cardiovascular complications), which occur in the neonatal period, and long-term sequelae (eg, neurodevelopmental disabilities such as cerebral palsy) in patients who survive and are discharged from the neonatal intensive care unit (NICU) [7]. Short-term complications result from anatomic or functional immaturity during the neonatal period. These complications contribute to the increased risk of long-term disability in this population. (See "Overview of the long-term complications of preterm birth".)

Hypothermia

Mechanism and risk factors — Rapid heat loss occurs in preterm infants because of their relatively large body surface area and inability to produce enough heat. Heat is lost by conduction, convection, radiation, and evaporation.

In preterm infants, especially EPT infants, hypothermia is associated with increased mortality and, in survivors, intraventricular hemorrhage (IVH), and pulmonary insufficiency and hemorrhage [8-14]. Hypothermia may contribute to metabolic disorders such as hypoglycemia or acidosis.

Preterm infants are at greatest risk for hypothermia immediately after birth in the delivery room and on admission to NICU. This was illustrated in a multicenter study of >9000 preterm infants (<34 weeks), of whom approximately 40 percent had body temperatures <36.5°C upon admission to the neonatal intensive care unit [11].

Reported risk factors for hypothermia include [12,13]:

●Delivery room temperature <25°C

●Maternal temperature <36°C

●Lack of heat loss preventive measures (eg, plastic bag/wrap, head covering)

●Decreasing BW

●Cesarean delivery

●Use of respiratory support with cold air

Prevention of hypotherrmia — Measures to prevent hypothermia in the delivery room and NICU include:

●Maintaining the delivery room temperature at a minimum of 26°C [15]

●Drying the baby thoroughly immediately after birth

●Removing of any wet blankets

●Encouraging skin-to-skin contact in healthy stable neonates

●Using prewarmed radiant heaters if resuscitation is necessary

●For neonates <30 weeks GA or <1500 g, additional measures used in the delivery room include plastic wraps, caps, and warming mattresses [16,17]

●When transporting preterm neonates, a closed incubator should be used

●Once in the NICU, preterm infants should be cared for in an incubator or radiant warmer

●Neonates who require advanced respiratory support should receive heated and humidified gas mixtures

The efficacy of plastic bags and wraps, caps, and warming mattresses is supported by several small clinical trials demonstrating that use of these interventions in the delivery room is associated with higher core temperature upon admission to the NICU [16,17]; however, it remains uncertain whether these interventions impact longer term outcomes or mortality.

Management of hypothermia — For neonates with significant hypothermia (rectal temperature <35°C), we use a radiant warmer to rapidly correct body temperature. Although, slow warming (increase <0.5° C per hour) was traditionally the approach to warming infants [8,9]; data are insufficient to determine if there is an advantage of one approach over the other (rapid versus slow warming).

Resource-limited settings — In resource-limited countries, the use of polyethylene bags for preterm infants with GA appears to decrease the incidence of hypothermia [9,18]. In addition, skin-to-skin contact or kangaroo care may be used. However, an observational study reported that the addition of a woolen cap during kangaroo care did not provide any additional benefit to low BW infants (BW <2500 g). Additional efforts are being made to develop alternatives for thermoregulation control in resource-limited settings, including conductive thermal mattresses [19].

Respiratory complications — Respiratory complications of prematurity include the following:

Respiratory distress syndrome (RDS) — RDS is caused by surfactant deficiency. The incidence and severity of RDS increase with decreasing GA. (See "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis".)

Bronchopulmonary dysplasia (BPD) — BPD is a late respiratory complication that commonly occurs in VLBW infants. It is generally defined as an ongoing need for supplemental oxygen and/or respiratory support at either 28 days postnatal age or 36 weeks postmenstrual age (PMA). (See "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis".)

Apnea of prematurity — Apnea of prematurity is a developmental disorder in preterm infants that is a consequence of immature respiratory control. (See "Pathogenesis, clinical manifestations, and diagnosis of apnea of prematurity".)

Other respiratory morbidity — Other respiratory complications seen in preterm neonates include pneumothorax and pulmonary hemorrhage. (See "Pulmonary air leak in the newborn".)

Pulmonary hemorrhage occurs most commonly in EPT infants and may be a consequence of patent ductus arteriosus (PDA). (See "Patent ductus arteriosus (PDA) in preterm infants: Clinical features and diagnosis", section on 'Consequences of a PDA'.)

In a large retrospective review of data from the multicenter Pediatrix United States Neonatal Intensive Care Units, the overall incidence of pulmonary hemorrhage was 0.5 percent, with a peak incidence of 9 percent among infants born at 24 weeks gestation [20]. In this cohort, infants with pulmonary hemorrhage had a higher mortality rate than those without pulmonary hemorrhage at seven days of age (41 versus 19 percent), 30 days of age (54 versus 29 percent), and prior to discharge (57 versus 34 percent).

Cardiovascular complications — Cardiovascular complications in the preterm infant include patent ductus arteriosus (PDA) and systemic hypotension.

Patent ductus arteriosus — A patent ductus arteriosus (PDA) occurs when the ductus arteriosus fails to completely close after delivery (figure 1). This is common in preterm infants, especially EPT infants. The PDA shunts blood flow from left-to-right resulting in increased flow through the pulmonary circulation and decreased perfusion of the systemic circulation. The physiologic consequences of the PDA depend upon the size of the shunt and the response of the heart and lungs to the shunt. Significant shunting may present with a variety of symptoms including apnea, respiratory distress, or heart failure. PDA in the preterm infant is discussed in greater detail separately. (See "Patent ductus arteriosus (PDA) in preterm infants: Clinical features and diagnosis".)

Low blood pressure — Low blood pressure (BP) is common in preterm neonates, especially in EPT infants. Low BP is sometimes associated with clinical signs of poor perfusion (ie, shock) and this likely contributes to increased risk of long-term morbidity and mortality. However, many EPT neonates with low BP otherwise appear well and it is unclear whether these neonates are at increased risk for complications. The evaluation and management of neonatal shock and the challenges of determining when low BP in EPT infants warrants intervention are discussed separately. (See "Neonatal shock: Etiology, clinical manifestations, and evaluation" and "Neonatal shock: Management" and "Assessment and management of low blood pressure in extremely preterm infants".)

Intraventricular hemorrhage — Intraventricular hemorrhage (IVH) usually occurs in the fragile germinal matrix and increases in frequency with decreasing BW. General preventive measures include prompt and appropriate resuscitation. In addition, efforts should be made to avoid hemodynamic instability and conditions that impair cerebral autoregulation (eg, hypoxia, hypercarbia, hyperoxia, and hypocarbia). (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis" and "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and outcome".)

Glucose abnormalities — Disorders in glucose supply or metabolism can result in hypoglycemia or hyperglycemia. Blood glucose concentration should be monitored routinely starting within one to two hours after birth and continued until feedings are well established and glucose values have normalized. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia" and "Neonatal hyperglycemia".)

Necrotizing enterocolitis — Necrotizing enterocolitis (NEC) occurs in 2 to 10 percent of VLBW infants. NEC is associated with an increase in mortality. Survivors are at increased risk for growth delay and neurodevelopmental disabilities. In addition, approximately 10 percent of preterm infants with NEC will have long-term gastrointestinal difficulties with persistent loose stools or frequent bowel movements.

The clinical features and treatment of NEC are discussed in detail separately. (See "Neonatal necrotizing enterocolitis: Clinical features and diagnosis" and "Neonatal necrotizing enterocolitis: Management and prognosis".)

Infection — Preterm infants are at increased risk for:

●Bacterial sepsis (see "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation")

●Fungal infections, particularly candida infections (see "Clinical manifestations and diagnosis of Candida infection in neonates")

●Viral infections, including:

•Cytomegalovirus infection (acquired from breast milk or blood transfusion) (see "Overview of cytomegalovirus infections in children", section on 'Early postnatal infection')

•Nosocomial respiratory infections (eg, due to respiratory syncytial virus or other respiratory pathogens) (see "Respiratory syncytial virus infection: Clinical features and diagnosis in infants and children")

•Other systemic viral infections (eg, enterovirus or parechovirus) (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Neonates')

Feeding difficulties — Preterm neonates have high nutritional needs and often have feeding difficulties due poor coordination of sucking and swallowing. In addition, they often have medical conditions that impede growth. As a result, growth failure is a major problem in this population. These issues are discussed in detail separately. (See "Neonatal oral feeding difficulties due to sucking and swallowing disorders" and "Breastfeeding the preterm infant" and "Growth management in preterm infants" and "Approach to enteral nutrition in the premature infant".)

Anemia of prematurity — Preterm infants are at high risk of clinically significant anemia because they have lower hemoglobin (Hgb) values at birth compared with term infants and the postnatal decline in Hgb occurs earlier and is more pronounced than the physiologic anemia seen in term infants. This is compounded by other factors (blood loss from phlebotomy, reduced red blood cell lifespan, depleted iron stores). Together, these processes are referred to as anemia of prematurity. Approximately 50 percent on preterm neonates <30 weeks GA require at least one transfusion during their NICU stay. (See "Anemia of prematurity (AOP)" and "Red blood cell (RBC) transfusions in the neonate", section on 'Prevalence of transfusion'.)

Retinopathy of prematurity — Retinopathy of prematurity (ROP) is a developmental vascular proliferative disorder that occurs in the incompletely vascularized retina of preterm infants. The incidence and severity of ROP increase with decreasing GA or BW. The condition typically begins at approximately 34 weeks PMA, although it may be seen as early as 30 to 32 weeks. ROP advances irregularly until 40 to 45 weeks PMA and resolves spontaneously in the majority of infants. However, patients with severe untreated ROP are at increased risk for poor ocular outcome with vision impairment.

ROP and its management are discussed in detail separately. (See "Retinopathy of prematurity (ROP): Risk factors, classification, and screening".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient education: What to expect in the NICU (The Basics)" and "Patient education: Retinopathy of prematurity (ROP) (The Basics)" and "Patient education: When a baby is born premature (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Importance ‒ Preterm birth (ie, delivery at <37 weeks gestational age [GA]) is a contributing factor in approximately one-third of all infant deaths in the United States. Complications of prematurity are the underlying reasons for the higher rate of infant mortality and morbidity in preterm infants compared with full-term infants. The risk of complications increases with decreasing GA and birth weight (BW). (See 'Introduction' above and 'Epidemiology' above.)

●Short-term complications – The short-term complications most commonly seen include:

•Hypothermia occurs due to rapid heat loss in preterm infants because of their relatively large body surface area and inability to produce enough heat. Hypothermia is associated with increased mortality and, in survivors, intraventricular hemorrhage (IVH), pulmonary insufficiency, hemorrhage, and metabolic disorders (eg, hypoglycemia or acidosis). (See 'Mechanism and risk factors' above.)

Measures to prevent hypothermia in the delivery room and neonatal intensive care unit (NICU) include (see 'Prevention of hypotherrmia' above):

-Maintaining the delivery room temperature at a minimum of 26°C

-Drying the baby thoroughly immediately after birth

-Removing of any wet blankets

-Encouraging skin-to-skin contact in healthy stable neonates

-Using prewarmed radiant heaters if resuscitation is necessary

-For, neonates <30 weeks GA or <1500 g, additional measures used in the delivery room include plastic wraps, caps, and warming mattresses

-When transporting preterm neonates, a closed incubator should be used

-Once in the NICU, preterm infants should be cared for in an incubator or radiant warmer

-Neonates who require advanced respiratory support should receive heated and humidified gas mixtures

•Respiratory complications of prematurity include:

-Respiratory distress syndrome (RDS) (see "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis")

-Bronchopulmonary dysplasia (BPD) (see "Bronchopulmonary dysplasia (BPD): Clinical features and diagnosis")

-Apnea of prematurity (see "Pathogenesis, clinical manifestations, and diagnosis of apnea of prematurity")

•Cardiovascular complications include:

-Patent ductus arteriosus (PDA) (see "Patent ductus arteriosus (PDA) in preterm infants: Clinical features and diagnosis")

-Low blood pressure (see "Assessment and management of low blood pressure in extremely preterm infants")

-Shock (see "Neonatal shock: Etiology, clinical manifestations, and evaluation")

•Other complications include:

-Intraventricular hemorrhage (see "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis")

-Abnormal glucose homeostasis leading to hypo- or hyperglycemia (see "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia" and "Neonatal hyperglycemia")

-Necrotizing enterocolitis (see "Neonatal necrotizing enterocolitis: Clinical features and diagnosis")

-Bacterial and fungal infections (see "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation" and "Clinical manifestations and diagnosis of Candida infection in neonates")

-Feeding difficulties and poor growth (see "Neonatal oral feeding difficulties due to sucking and swallowing disorders" and "Breastfeeding the preterm infant" and "Growth management in preterm infants" and "Approach to enteral nutrition in the premature infant")

-Anemia of prematurity (see "Anemia of prematurity (AOP)")

-Retinopathy of prematurity (see "Retinopathy of prematurity (ROP): Risk factors, classification, and screening")