Preterm Infants

The American College of Obstetricians and Gynecologists (ACOG) recommends late preterm delivery in conditions such as multiple gestation with complications, preeclampsia, placenta previa/placenta accreta, and prelabor rupture of membranes (1).

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 and Infectious Disease in Pregnancy], placental abruption). There are many risk factors (2):

Past obstetric or gynecologic history:

• Prior preterm birth (highest risk)

• Prior cervical conization procedure (cold knife cone or loop electrosurgical excision procedure)

• Prior dilation and curettage procedure for spontaneous abortion or therapeutic abortion (3)

• Cervical insufficiency, cervical polyps, uterine fibroids, or maternal congenital reproductive tract abnormalities (eg, bicornuate uterus)

• Chronic diabetes

• Hypertension

• Kidney disease

Obstetric risk factors related to the current pregnancy:

• Short interpregnancy interval (< 6 months) 

• Extremes of prepregnancy weight (underweight or obese) or of weight gain during pregnancy (gaining more or less weight than recommended)

• Pregnancy achieved by in vitro fertilization

• Multiple gestation (eg, twins, triplets)

• Vaginal bleeding in early pregnancy

• Placental abruption or placenta previa

• Preterm labor

• Preeclampsia

• Infections (eg, bacterial vaginosis, trichomoniasis, urinary tract infection, sexually transmitted infection, intra-amniotic infection)

• Chronic diabetes or gestational diabetes

• Prelabor rupture of membranes

• Little or no prenatal care

• Certain congenital defects (fetuses with structural congenital heart defects are nearly twice as likely to be delivered prematurely as fetuses without congenital heart defects)

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).

Lifestyle or demographic risk factors:

• Younger or older maternal age (eg, < 16 years, > 35 years)

• Non-Hispanic Black or American Indian/Alaska Native women (in the United States)

• Undernutrition

• Cigarette smoking

• Use of alcohol or illicit drugs

• Exposure to certain environmental pollutants

• Domestic violence

• Stress or lack of social support

• Long work hours with long periods of standing

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).

1. 1. American College of Obstetricians and Gynecologists’ Committee on Obstetric Practice, Society for Maternal-Fetal Medicine: Medically Indicated Late-Preterm and Early-Term Deliveries: ACOG Committee Opinion, Number 831. Obstet Gynecol 138(1):e35-e39, 2021. doi: 10.1097/AOG.0000000000004447

2. 2. National Institute of Child Health and Human Development: What are the risk factors for preterm labor and birth? Accessed October 6, 2023.

3. 3. Saccone G, Perriera L, Berghella V: Prior uterine evacuation of pregnancy as independent risk factor for preterm birth: A systematic review and metaanalysis. Am J Obstet Gynecol 214(5):572-591, 2016. doi: 10.1016/j.ajog.2015.12.044

4. 4. Hamilton BE, Martin JA, Osterman MJ: Births: Provisional Data for 2021. National Center for Health Statistics. National Vital Statistics System, Vital Statistics Rapid Release Program, no 20. Hyattsville, MD. National Center for Health Statistics. 2022.

CNS complications include

• Poor sucking and swallowing reflexes

• Apneic episodes

• Intraventricular hemorrhage

• Developmental and/or cognitive delays

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). Apnea may also result from hypopharyngeal obstruction alone (obstructive apnea). Both may be present (mixed apnea).

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). 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 and neurodevelopmental delays.

Preterm infants, particularly those with a history of sepsis, necrotizing enterocolitis, hypoxia, and intraventricular and/or periventricular hemorrhages or leukomalacia, are at risk of developmental and cognitive delays (see also Childhood Development). 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, muscle tone, language skills, and growth (weight, length, and head circumference). 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

• Retinopathy of prematurity (ROP)

• Myopia and/or strabismus

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

• Meningitis

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).

Pulmonary complications include

• Respiratory distress syndrome

• Respiratory insufficiency of prematurity

• Chronic lung disease (bronchopulmonary dysplasia)

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 (CPAP) or other noninvasive ventilatory assistance, or mechanical ventilation. 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 Neonatal Oxygen Saturation Targets).

respiratory syncytial virus (RSV)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). 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, with increased risk of aspiration

• Necrotizing enterocolitis

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 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

• Patent ductus arteriosus (PDA)

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 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

• Metabolic acidosis

• Growth failure

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

• Hypoglycemia and hyperglycemia

• Hyperbilirubinemia

• Metabolic bone disease (osteopenia of prematurity)

• Congenital hypothyroidism

Neonatal hypoglycemia and neonatal hyperglycemia are discussed elsewhere.

Hyperbilirubinemia occurs more commonly in the preterm as compared to the term infant, and kernicterus (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

Congenital hypothyroidism, 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).

The most common temperature regulation complication is

• Hypothermia

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.

1. 1. American College of Obstetricians and Gynecologists: Practice Advisory: Maternal Respiratory Syncytial Virus Vaccination. 2023. Accessed October 6, 2023.

2. 2. Wassner AJ, Brown RS: Hypothyroidism in the newborn period. Curr Opin Endocrinol Diabetes Obes 20(5):449–454, 2013. doi: 10.1097/01.med.0000433063.78799.c2

1. 1. Clark RH, Kelleher AS, Chace DH, Spitzer AR: Gestational age and age at sampling influence metabolic profiles in premature infants. Pediatrics 134(1):e37–e46, 2014. doi: 10.1542/peds.2014-0329