Preterm Infants

The American College of Obstetricians and Gynecologists (ACOG) recommends late preterm delivery in conditions such as multiple gestation with complications Complications Multifetal pregnancy is presence of > 1 fetus in the uterus. Multifetal (multiple) pregnancy occurs in up to 1 of 30 deliveries. Risk factors for multiple pregnancy include Ovarian stimulation... read more , preeclampsia Preeclampsia and Eclampsia Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis... read more , placenta previa Placenta Previa Placenta previa is implantation of the placenta over or near the internal os of the cervix. It typically manifests as painless vaginal bleeding after 20 weeks gestation; the source of bleeding... read more / placenta accreta Placenta Accreta Placenta accreta is an abnormally adherent placenta, resulting in delayed delivery of the placenta. Placental function is normal, but trophoblastic invasion extends beyond the normal boundary... read more , and prelabor rupture of membranes Prelabor Rupture of Membranes (PROM) Prelabor rupture of membranes is leakage of amniotic fluid before onset of labor. Diagnosis is clinical. Delivery is recommended when gestational age is ≥ 34 weeks and is generally indicated... read more (1 Etiology references An infant born before 37 weeks of gestation is considered preterm. In 2021 in the United States, 10.48% of births were preterm ( 1), and in 2018, 26.53% of births were early term (significantly... read more ).

ACOG recommends delivery as early as 32 weeks in selected cases involving multiple gestation with complications. Quasi-elective delivery earlier than 32 weeks is done on a case-by-case basis to manage severe maternal and/or fetal complications.

In an individual patient, spontaneous preterm delivery may or may not have an obvious immediate trigger (eg, infection [see Intra–Amniotic Infection Intraamniotic Infection Intraamniotic infection is infection of the chorion, amnion, amniotic fluid, placenta, or a combination. Infection increases risk of obstetric complications and problems in the fetus and neonate... read more and Infectious Disease in Pregnancy Infectious Disease in Pregnancy Most common maternal infections (eg, UTIs, skin and respiratory tract infections) are usually not serious problems during pregnancy, although some genital infections (bacterial vaginosis and... read more ], placental abruption Placental Abruption (Abruptio Placentae) Placental abruption (abruptio placentae) is premature separation of the placenta from the uterus, usually after 20 weeks gestation. It can be an obstetric emergency. Manifestations may include... read more ). There are many risk factors (2 General references An infant born before 37 weeks of gestation is considered preterm. In 2021 in the United States, 10.48% of births were preterm ( 1), and in 2018, 26.53% of births were early term (significantly... read more ):

Past obstetric or gynecologic history:

Obstetric risk factors related to the current pregnancy:

Multiple gestation is an important risk factor; 59% of twins and > 98% of higher-order multiples are delivered prematurely. Many of these infants are very preterm; 10.7% of twins, 37% of triplets, and > 80% of higher-order multiples are delivered at < 32 weeks of gestation (4 General references An infant born before 37 weeks of gestation is considered preterm. In 2021 in the United States, 10.48% of births were preterm ( 1), and in 2018, 26.53% of births were early term (significantly... read more ).

Lifestyle or demographic risk factors:

It is unclear how much risk some of these lifestyle or demographic risk factors contribute independent of their effect on other risk factors (eg, nutrition, access to medical care).

CNS complications include

Infants born before 34 weeks of gestation have inadequate coordination of sucking and swallowing reflexes and need to be fed intravenously or by gavage. When to begin oral feedings is based on the infant's display of readiness cues for feeding, physiologic stability, and lack of need for advanced respiratory support (eg, ventilator, high-flow nasal catheters, CPAP). Evaluation for signs of feeding readiness does not begin until after 32 weeks postmenstrual age.

Immaturity of the respiratory center in the brain stem results in apneic spells (central apnea Pathophysiology Apnea of prematurity is defined as respiratory pauses > 20 seconds or pauses < 20 seconds that are associated with bradycardia (< 100 beats/minute; 1), central cyanosis, and/or oxygen... read more ). Apnea may also result from hypopharyngeal obstruction alone (obstructive apnea Pathophysiology Apnea of prematurity is defined as respiratory pauses > 20 seconds or pauses < 20 seconds that are associated with bradycardia (< 100 beats/minute; 1), central cyanosis, and/or oxygen... read more ). Both may be present (mixed apnea Pathophysiology Apnea of prematurity is defined as respiratory pauses > 20 seconds or pauses < 20 seconds that are associated with bradycardia (< 100 beats/minute; 1), central cyanosis, and/or oxygen... read more ).

The periventricular germinal matrix (a highly cellular mass of embryonic cells that lies over the caudate nucleus on the lateral wall of the lateral ventricles of a fetus) is prone to hemorrhage, which may extend into the cerebral ventricles (intraventricular hemorrhage Intraventricular hemorrhage and/or intraparenchymal hemorrhage The forces of labor and delivery occasionally cause physical injury to the infant. The incidence of neonatal injury resulting from difficult or traumatic deliveries is decreasing due to increasing... read more ). Infarction of the periventricular white matter (periventricular leukomalacia) may also occur for reasons that are incompletely understood. Hypotension, inadequate or unstable brain perfusion, and blood pressure peaks (as when fluid or colloid is given rapidly IV) may contribute to cerebral infarction or hemorrhage. Periventricular white matter injury is a major risk factor for cerebral palsy Cerebral Palsy (CP) Cerebral palsy refers to a group of nonprogressive conditions characterized by impaired voluntary movement or posture and resulting from prenatal developmental malformations or perinatal or... read more and neurodevelopmental delays.

Preterm infants, particularly those with a history of sepsis Neonatal Sepsis Neonatal sepsis is invasive infection, usually bacterial, occurring during the neonatal period. Signs are multiple, nonspecific, and include diminished spontaneous activity, less vigorous sucking... read more , necrotizing enterocolitis Necrotizing Enterocolitis Necrotizing enterocolitis is an acquired disease, primarily of preterm or sick neonates, characterized by mucosal or even deeper intestinal necrosis. It is the most common gastrointestinal emergency... read more , hypoxia, and intraventricular and/or periventricular hemorrhages or leukomalacia, are at risk of developmental and cognitive delays (see also Childhood Development Childhood Development Descriptions of development are often divided into specific domains, such as gross motor, fine motor, language, cognition, and social/emotional growth. These designations are useful, but substantial... read more ). These infants require careful follow-up during the first year of life to identify auditory, visual, and neurodevelopmental delays. Careful attention must be paid to developmental milestones Developmental Milestones* , muscle tone, language skills Language and Speech Development Descriptions of development are often divided into specific domains, such as gross motor, fine motor, language, cognition, and social/emotional growth. These designations are useful, but substantial... read more , and growth Physical Growth of Infants and Children Physical growth includes attainment of full height and appropriate weight and an increase in size of all organs (except lymphatic tissue, which decreases in size). Growth from birth to adolescence... read more (weight Weight Physical growth includes attainment of full height and appropriate weight and an increase in size of all organs (except lymphatic tissue, which decreases in size). Growth from birth to adolescence... read more , length Length Physical growth includes attainment of full height and appropriate weight and an increase in size of all organs (except lymphatic tissue, which decreases in size). Growth from birth to adolescence... read more , and head circumference Head Circumference Physical growth includes attainment of full height and appropriate weight and an increase in size of all organs (except lymphatic tissue, which decreases in size). Growth from birth to adolescence... read more ). Infants with identified delays in visual skills should be referred to a pediatric ophthalmologist. Infants with auditory and neurodevelopmental delays (including increased muscle tone and abnormal protective reflexes) should be referred to early intervention programs that provide physical, occupational, and speech therapy. Infants with severe neurodevelopmental problems may need to be referred to a pediatric neurologist or neurodevelopmental pediatrician.

Ocular complications include

Retinal vascularization is not complete until near term. Preterm delivery and the therapies needed to treat it (eg, supplemental oxygen) may interfere with the normal vascularization process, resulting in abnormal vessel development and sometimes defects in vision including blindness. Incidence of ROP is inversely proportional to gestational age. Disease usually manifests between 32 weeks and 34 weeks of gestational age.

Incidence of myopia and strabismus increases independently of ROP.

Infectious complications include

Sepsis or meningitis is about 4 times more likely in the preterm infant, occurring in almost 25% of very low-birthweight infants. The increased likelihood results from indwelling intravascular catheters and endotracheal tubes, areas of skin breakdown, and markedly reduced serum immunoglobulin levels (see Neonatal Immunologic Function Neonatal Immunologic Function The transition from life in utero to life outside the womb involves multiple changes in physiology and function. See also Perinatal Problems. (See also Liver Structure and Function and Neonatal... read more ).

Pulmonary complications include

Surfactant production is often inadequate to prevent alveolar collapse and atelectasis, which result in respiratory distress syndrome (hyaline membrane disease). Many other factors can contribute to respiratory distress in the first week of life. Regardless of the cause, many extremely preterm and very preterm infants have persistent respiratory distress and an ongoing need for respiratory support. Some infants are successfully weaned off support over a few weeks; others develop chronic lung disease (bronchopulmonary dysplasia) with need for prolonged respiratory support using a high-flow nasal cannula, continuous positive airway pressure Continuous Positive Airway Pressure (CPAP) Initial stabilization maneuvers include mild tactile stimulation, head positioning, and suctioning of the mouth and nose followed as needed by Supplemental oxygen Continuous positive airway... read more (CPAP) or other noninvasive ventilatory assistance, or mechanical ventilation Mechanical Ventilation Initial stabilization maneuvers include mild tactile stimulation, head positioning, and suctioning of the mouth and nose followed as needed by Supplemental oxygen Continuous positive airway... read more . Respiratory support may be given with room air or with supplemental oxygen. If supplemental oxygen is required, the lowest oxygen concentration that can maintain target oxygen saturation levels of 90 to 95% should be used (see table ).

Nirsevimab prophylaxis for respiratory syncytial virus (RSV) Prevention Respiratory syncytial virus and human metapneumovirus infections cause seasonal lower respiratory tract disease, particularly in infants and young children. Disease may be asymptomatic, mild... read more is important for infants with chronic lung disease. Palivizumab may be used if nirsevimab is not available.

In addition, the American College of Obstetricians and Gynecologists recommends maternal RSV vaccination between 32 and 36 6/7 weeks of gestation, if birth is expected during the RSV season, to prevent RSV lower respiratory tract infection in infants (1 Complications references An infant born before 37 weeks of gestation is considered preterm. In 2021 in the United States, 10.48% of births were preterm ( 1), and in 2018, 26.53% of births were early term (significantly... read more ). However, it is uncertain whether maternal RSV vaccination will benefit many preterm infants because timing of birth may not allow timely administration of the vaccine.

Gastrointestinal complications include

Feeding intolerance is extremely common because preterm infants have a small stomach, immature sucking and swallowing reflexes, and inadequate gastric and intestinal motility. These factors hinder the ability to tolerate both oral and nasogastric feedings and create a risk of aspiration. Feeding tolerance usually increases over time.

Necrotizing enterocolitis Necrotizing Enterocolitis Necrotizing enterocolitis is an acquired disease, primarily of preterm or sick neonates, characterized by mucosal or even deeper intestinal necrosis. It is the most common gastrointestinal emergency... read more usually manifests with bloody stool, feeding intolerance, and a distended, tender abdomen. Necrotizing enterocolitis is the most common surgical emergency in the preterm infant. Complications of neonatal necrotizing enterocolitis include bowel perforation with pneumoperitoneum, intra-abdominal abscess formation, stricture formation, short bowel syndrome, septicemia, and death.

The overall incidence of structural congenital heart defects among preterm infants is low. The most common cardiac complication is

The ductus arteriosus is more likely to fail to close after birth in preterm infants. The incidence of PDA increases with increasing prematurity; PDA occurs in almost half of infants whose birthweight is < 1750 g and in about 80% of those < 1000 g. About one third to one half of infants with PDA have some degree of heart failure. Preterm infants ≤ 29 weeks of gestation at birth who have respiratory distress syndrome Respiratory Distress Syndrome in Neonates Respiratory distress syndrome is caused by pulmonary surfactant deficiency in the lungs of neonates, most commonly in those born at < 37 weeks gestation. Risk increases with degree of prematurity... read more have a 65 to 88% risk of a symptomatic PDA. If infants are ≥ 30 weeks of gestation at birth, the ductus closes spontaneously in 98% by the time of hospital discharge.

Renal complications include

Renal function is limited, so the concentrating and diluting limits of urine are decreased.

Late metabolic acidosis and growth failure may result from the immature kidneys’ inability to excrete fixed acids, which accumulate with high-protein formula feedings and as a result of bone growth. Sodium and bicarbonate are lost in the urine.

Metabolic complications include

Neonatal hypoglycemia Neonatal Hypoglycemia Hypoglycemia is difficult to define in neonates but is generally considered a serum glucose concentration < 40 mg/dL (< 2.2 mmol/L) in symptomatic term neonates, < 45 mg/dL (< 2... read more and neonatal hyperglycemia Neonatal Hyperglycemia Hyperglycemia is a serum glucose concentration > 150 mg/dL (> 8.3 mmol/L). Diagnosis is with serum glucose testing. Treatment is reduction of the IV dextrose concentration or of the infusion... read more are discussed elsewhere.

Hyperbilirubinemia Neonatal Hyperbilirubinemia Jaundice is a yellow discoloration of the skin and eyes caused by hyperbilirubinemia (elevated serum bilirubin concentration). The serum bilirubin level required to cause jaundice varies with... read more occurs more commonly in the preterm as compared to the term infant, and kernicterus Kernicterus Kernicterus is brain damage caused by unconjugated bilirubin deposition in basal ganglia and brain stem nuclei. Normally, bilirubin bound to serum albumin stays in the intravascular space. However... read more (brain damage caused by hyperbilirubinemia) may occur at serum bilirubin levels as low as 10 mg/dL (170 micromol/L) in small, sick, preterm infants. The higher bilirubin levels may be partially due to hepatic excretion mechanisms that are inadequately developed for extrauterine life, including deficiencies in the uptake of bilirubin from the serum, its hepatic conjugation to bilirubin diglucuronide, and its excretion into the biliary tree. Decreased intestinal motility enables more bilirubin diglucuronide to be deconjugated within the intestinal lumen by the luminal enzyme beta-glucuronidase, thus permitting increased reabsorption of unconjugated bilirubin (enterohepatic circulation of bilirubin). Conversely, early feedings increase intestinal motility and reduce bilirubin reabsorption and can thereby significantly decrease the incidence and severity of physiologic jaundice. Uncommonly, delayed clamping of the umbilical cord (which has several benefits and is generally recommended) may increase the risk of hyperbilirubinemia by allowing the transfusion of RBCs thus increasing RBC breakdown and bilirubin production.

Metabolic bone disease with osteopenia is common, particularly in extremely preterm infants. It is caused by inadequate intake of calcium, phosphorus, and vitamin D and is exacerbated by administration of diuretics and corticosteroids. Breast milk also has insufficient calcium and phosphorus and must be fortified. Supplemental vitamin D is necessary to optimize intestinal absorption of calcium and control urinary excretion.

Congenital hypothyroidism Hypothyroidism in Infants and Children Hypothyroidism is thyroid hormone deficiency. Symptoms in infants include poor feeding and growth failure; symptoms in older children and adolescents are similar to those of adults but also... read more , characterized by low thyroxine (T4) and elevated thyroid-stimulating hormone (TSH) levels, is much more common among preterm infants than full-term infants. In infants with a birthweight of < 1500 g, the rise in TSH may be delayed for several weeks, necessitating repeated screening for detection. Transient hypothyroxinemia, characterized by low T4 and normal TSH levels, is very common among extremely preterm infants; treatment with L-thyroxine is not beneficial (2 Complications references An infant born before 37 weeks of gestation is considered preterm. In 2021 in the United States, 10.48% of births were preterm ( 1), and in 2018, 26.53% of births were early term (significantly... read more ).

The most common temperature regulation complication is

Preterm infants have an exceptionally large body surface area to volume ratio. Therefore, when exposed to temperatures below the neutral thermal environment, they rapidly lose heat and have difficulty maintaining body temperature. The neutral thermal environment is the environmental temperature at which metabolic demands (and thus calorie expenditure) to maintain normal body temperature (36.5 to 37.5° C rectal) are lowest.