Prematurity is defined by the gestational age Gestational Age Gestational age and growth parameters help identify the risk of neonatal pathology. Gestational age is the primary determinant of organ maturity. Gestational age is usually defined as the number... read more at which infants are born. Previously, any infant weighing < 2.5 kg was termed preterm. Although preterm infants tend to be small, this weight-based definition is incorrect because many infants weighing < 2.5 kg are term or postterm Postterm Infants A postterm infant is an infant born after 42 weeks gestation. The cause of postmaturity is generally unknown, but previous postterm delivery increases the risk 2- to 3-fold. Postmaturity may... read more and small for gestational age Small-for-Gestational-Age (SGA) Infant Infants whose weight is < the 10th percentile for gestational age are classified as small for gestational age. Complications include perinatal asphyxia, meconium aspiration, polycythemia... read more ; they have a different appearance and different problems.
In 2021 in the US, 10.48% of births were preterm (1 General references An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ), and in 2018, 26.53% of births were early term (significantly increased from 26% in 2017) (2 General references An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ). Preterm infants, even late preterm infants who are the size of some full-term infants, have increased morbidity and mortality compared to full-term infants due to their prematurity.
Gestational age
Gestational age Gestational Age Gestational age and growth parameters help identify the risk of neonatal pathology. Gestational age is the primary determinant of organ maturity. Gestational age is usually defined as the number... read more is loosely defined as the number of weeks between the first day of the mother's last normal menstrual period and the day of delivery. More accurately, the gestational age is the difference between 14 days before the date of conception and the date of delivery. Gestational age is not the actual embryologic age of the fetus, but it is the universal standard among obstetricians and neonatologists for discussing fetal maturation.
Birth prior to 37 weeks gestation is considered preterm. Preterm infants are further categorized as
Birthweight
Preterm infants tend to be smaller than term infants. The Fenton growth charts provide a more precise assessment of growth vs gestational age ( see Figure: Fenton growth chart for preterm boys Fenton growth chart for preterm boys and see Figure: Fenton growth chart for preterm girls Fenton growth chart for preterm girls
).
Preterm infants are categorized by birthweight:
< 1000 g: Extremely low birthweight (ELBW)
1000 to 1499 g: Very low birthweight (VLBW)
1500 to 2500 g: Low birthweight (LBW)
General references
1. 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.
2. Martin JA, Hamilton BE, Osterman MJ: Births in the United States, 2018. NCHS Data Brief, no 346. Hyattsville, MD. National Center for Health Statistics. 2019.
Etiology of Prematurity
Preterm delivery may be
Elective
Spontaneous
Elective preterm delivery
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 .
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.
Spontaneous preterm delivery
In a given 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:
Past obstetric history
Prior multiple therapeutic abortions Induced Abortion In the United States, about half of pregnancies are unintended. About 40% of unintended pregnancies end in induced abortion; 90% of procedures are done during the 1st trimester. In the United... read more and/or spontaneous miscarriages Spontaneous Abortion Spontaneous abortion is pregnancy loss before 20 weeks gestation. Threatened abortion is vaginal bleeding without cervical dilation before 20 weeks in a confirmed viable intrauterine pregnancy... read more
Current pregnancy-related factors
Little or no prenatal care
Poor nutrition during gestation (and perhaps before)
Untreated infections (eg, bacterial vaginosis Bacterial Vaginosis (BV) Bacterial vaginosis is a dysbiosis, a complex alteration of vaginal flora, in which lactobacilli decrease and anaerobic pathogens overgrow. Symptoms include a yellow-green or gray, thin, malodorous... read more
, 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 [formerly chorioamnionitis])
Certain congenital defects (fetuses with structural congenital heart defects Overview of Congenital Cardiovascular Anomalies Congenital heart disease is the most common congenital anomaly, occurring in almost 1% of live births ( 1). Among birth defects, congenital heart disease is the leading cause of infant mortality... read more
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 (1 General references An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ).
Socioeconomic factors
Low socioeconomic status
Mothers with less formal education
It is unclear how much risk these socioeconomic factors contribute independent of their effect on other risk factors (eg, nutrition, access to medical care).
Complications of Prematurity
The incidence and severity of complications of prematurity increase with decreasing gestational age and birthweight. Some complications (eg, necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage) are uncommon in late preterm infants.
Most complications relate to dysfunction of immature organ systems. In some cases, complications resolve completely; in others, there is residual organ dysfunction.
Cardiac
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 gestation at birth who have respiratory distress syndrome have a 65 to 88% risk of a symptomatic PDA. If infants are ≥ 30 weeks gestation at birth, the ductus closes spontaneously in 98% by the time of hospital discharge.
Central nervous system (CNS)
CNS complications include
Poor sucking and swallowing reflexes
Infants born before 34 weeks gestation have inadequate coordination of sucking and swallowing reflexes and need to be fed intravenously or by gavage.
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, 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.
Eyes
Ocular complications include
Retinal vascularization is not complete until near term. Preterm delivery 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 gestational age.
Incidence of myopia and strabismus increases independently of ROP.
Gastrointestinal tract
Gastrointestinal complications include
Feeding intolerance, with increased risk of aspiration
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.
Infection
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 ).
Kidneys
Renal complications include
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.
Lungs
Pulmonary complications include
Respiratory insufficiency of prematurity
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 (termed Wilson-Mikity disease, chronic pulmonary insufficiency of prematurity, or respiratory insufficiency of prematurity). 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: Neonatal Oxygen Saturation Targets Neonatal Oxygen Saturation Targets ).
Palivizumab prophylaxis for respiratory syncytial virus Respiratory Syncytial Virus (RSV) and Human Metapneumovirus Infections 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.
Metabolic problems
Metabolic complications include
Metabolic bone disease (osteopenia of prematurity)
Neonatal hypoglycemia 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 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 (1 Complications reference An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ).
Complications reference
1. 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
Temperature regulation
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.
Diagnosis of Prematurity
Obstetric history and postnatal physical parameters
Fetal ultrasonography
Screening tests for complications
When periods are regular and recorded contemporaneously, the menstrual history is relatively reliable for establishing gestational age. Ultrasonographic measurements of the fetus in the first trimester give the most accurate estimate of gestational age. Ultrasonographic estimates are less accurate later in pregnancy; second and third trimester ultrasonographic results should rarely be used to revise those done during the first trimester. After delivery, newborn physical examination findings also allow clinicians to estimate gestational age, which can be confirmed by the new Ballard score Assessment of Gestational Age—New Ballard Score .
Along with appropriate testing for any identified problems or disorders, routine evaluations include pulse oximetry, complete blood count, electrolytes, bilirubin level, blood culture, serum calcium, alkaline phosphatase, and phosphorus levels (to screen for osteopenia of prematurity), hearing evaluation, cranial ultrasonography (to screen for intraventricular hemorrhage and periventricular leukomalacia), and screening by an ophthalmologist for retinopathy of prematurity. Weight, length, and head circumference should be plotted on an appropriate growth chart at weekly intervals.
As with older neonates, routine newborn screening tests Screening Tests for Newborns Screening recommendations for newborns vary by clinical context and regulatory requirements. In the United States, the Health Resources & Services Administration recommends screening for all... read more are done at 24 to 48 hours of age. Unlike full-term infants, preterm infants, especially extremely preterm infants, have a high rate of false-positives (1 Diagnosis reference An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ). Mild elevations of several amino acids and abnormal acylcarnitine profiles are common and slight elevations of 17-hydroxyprogesterone levels and low thyroxine (T4) levels (typically with normal thyroid-stimulating hormone levels) are often present. Extremely preterm infants and very preterm infants are at risk of a delayed presentation of congenital hypothyroidism and should be periodically screened.
X-rays, often obtained for other reasons, may provide evidence of osteopenia and/or unsuspected fractures. DXA scanning Dual-energy x-ray absorptiometry (DXA) Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more and quantitative ultrasonography scanning may detect osteopenia but are not in widespread use.
Diagnosis reference
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
Preterm, Very Preterm, and Extremely Preterm Infants
Complications
The incidence and severity of complications of preterm infants Complications An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more increase with decreasing gestational age and birthweight. Some complications (eg, 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 , retinopathy of prematurity Retinopathy of Prematurity Retinopathy of prematurity is a bilateral disorder of abnormal retinal vascularization in premature infants, especially those of lowest birth weight. Outcomes range from normal vision to blindness... read more , bronchopulmonary dysplasia Bronchopulmonary Dysplasia (BPD) Bronchopulmonary dysplasia is chronic lung disease of the neonate that typically is caused by prolonged ventilation and is further defined by degree of prematurity and extent of supplemental... read more
, 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
) occur primarily in infants delivered at < 34 weeks.
Symptoms and Signs
The preterm infant is small, usually weighing < 2.5 kg, and tends to have thin, shiny, pink skin through which the underlying veins are easily seen. Little subcutaneous fat, hair, or external ear cartilage exists. Spontaneous activity and tone are reduced, and extremities are not held in the flexed position typical of term infants.
In males, the scrotum may have few rugae, and the testes may be undescended. In females, the labia majora do not yet cover the labia minora.
Reflexes develop at different times during gestation. The Moro reflex begins by 28 to 32 weeks gestation and is well established by 37 weeks. The palmar reflex starts at 28 weeks and is well established by 32 weeks. The tonic neck reflex starts at 35 weeks and is most prominent at 1 month postterm.
Evaluation
Monitoring in a neonatal intensive care unit (NICU)
Screening for complications
NICU monitoring and screening
Serial physical examinations are important in monitoring infants' progress and detecting new problems (eg, respiratory problems, jaundice). Frequent weight assessments are necessary to optimize weight-based drug dosage and feeding.
Growth and nutrition: Weight should be monitored closely, particularly in the first days of life when there is a contraction of the extracellular volume; dehydration with severe hypernatremia Neonatal Hypernatremia Hypernatremia is a serum sodium concentration > 150 mEq/L (> 150 mmol/L), usually caused by dehydration. Signs include lethargy and seizures. Treatment is cautious hydration with IV saline... read more may develop. Weight should be assessed daily if tolerated; length and head circumference should be assessed weekly and plotted on an appropriate growth chart.
Electrolyte balance: Serum electrolytes, glucose, calcium, and phosphate levels need to be periodically measured, particularly in infants receiving parenteral fluids and/or nutrition (eg, very preterm and extremely preterm infants), and during the diuresis seen in the first days of life.
Respiratory status: Pulse oximetry and sometimes transcutaneous or end-tidal PCO2 are monitored continually; arterial or capillary blood gas tests are done as needed.
Apnea and bradycardia: External cardiorespiratory monitoring is usually continued until discharge.
Hematologic abnormalities: Complete blood count (CBC), reticulocyte count, and differential count are done initially and at intervals to detect common abnormalities.
Hyperbilirubinemia: Transcutaneous and/or serum bilirubin levels are measured to detect and monitor this disorder.
Systemic infection: CBC, C-reactive protein, blood culture, and sometimes procalcitonin levels are often done to facilitate early detection of neonatal sepsis.
Central nervous system infection: Lumbar puncture is typically reserved for infants with clear signs of infection and/or seizures, a positive blood culture, or an infection that is not responding to antibiotics.
Intraventricular hemorrhage (IVH): Screening cranial ultrasonography is indicated at 7 to 10 days in preterm infants < 32 weeks and in older preterm infants with complex courses (eg, known IVH, cardiorespiratory and/or metabolic instability).
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 in extremely preterm infants is usually clinically silent, and a routine cranial ultrasound is recommended for these infants. The incidence of IVH decreases with increasing gestational age, so routine screening of preterm infants > 32 weeks is not considered useful unless they had significant complications. Most IVHs occur in the first week of life and, unless there are clinical indications of hemorrhage, the highest yield is obtained by scanning at 7 to 10 days of age. Extremely preterm infants are at risk of periventricular leukomalacia which may develop later in the course (with or without hemorrhage), so they should have cranial ultrasonography at 6 weeks of age. Infants with moderate or severe hemorrhages should be followed using head circumference measurements and periodic cranial ultrasonography to detect and monitor hydrocephalus; there is no benefit in repeat scanning of infants with minor hemorrhage. However, close neurodevelopmental follow-up is recommended for infants who have any hemorrhage.
Later screening
Screening for retinopathy of prematurity is recommended for infants born ≤ 1500 g or ≤ 30 weeks gestational age and for larger and more mature infants who have had an unstable clinical course. The first examination is done according to a schedule based on the infant's gestational age (see table Screening for Retinopathy of Prematurity Screening for Retinopathy of Prematurity ). Examinations are usually repeated at 1- to 3-week intervals depending on the initial findings and are continued until the retina is mature. Some of these follow-up examinations are done after the infant is discharged. The use of digital photographic retinal images is an alternate method of examination and follow-up in areas where a skilled examiner is not routinely available.
Screening for Retinopathy of Prematurity
Gestational Age at Birth | Gestational Age* at First Examination |
---|---|
22–27 weeks | 31 weeks |
28 weeks | 32 weeks |
29 weeks | 33 weeks |
30 weeks | 34 weeks |
* Postmenstrual gestational age. | |
Adapted from Fierson WM, American Academy of Pediatrics Section on Ophthalmology, American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American Association of Certified Orthoptists: Screening examination of premature infants for retinopathy of prematurity. Pediatrics 131(1):189–195, 2013. doi: 10.1542/peds.2012-2996 |
Evaluation reference
1. Narvey MR; Canadian Paediatric Society, Fetus and Newborn Committee: Assessment of cardiorespiratory stability using the infant car seat challenge before discharge in preterm infants (< 37 weeks' gestational age). Paediatr Child Health 21(3):155–162, 2016. doi: 10.1093/pch/21.3.155
Prognosis for Preterm Infants
Prognosis varies with presence and severity of complications, or the presence of multiple births, but usually mortality and likelihood of complications decrease greatly with increasing gestational age and birthweight (see figure Disability rates of singleton vs multiple births in preterm infants Disability rates of singleton vs multiple births in preterm infants ).
Disability rates of singleton vs multiple births in preterm infants
The rate of disability increases with increasing prematurity. For infants born before 25 weeks gestational age, the rate of disability for multiple births is higher than that for singletons (A) and, among multiple births, the rate of disability is higher for second and higher births than for the first infant delivered (B). (Adapted from Gnanendran L, Bajuk B, Oei J, et al: Neurodevelopmental outcomes of preterm singletons, twins and higher-order gestations: A population-based cohort study. Arch Dis Child Fetal Neonatal Ed 100(2):F106–F114, 2015. doi: 10.1136/archdischild-2013-305677) ![]() |
Treatment of Preterm Infants
Supportive care
Specific disorders are treated as discussed elsewhere in THE MANUAL. General supportive care of the preterm infant is best provided in a NICU or special care nursery and involves careful attention to the thermal environment, using servo-controlled incubators. Scrupulous adherence is paid to handwashing before and after all patient contact. Infants are continually monitored for apnea, bradycardia, and hypoxemia until 34.5 or 35 weeks gestation.
Parents should be encouraged to visit and interact with the infant as much as possible within the constraints of the infant’s medical condition. Skin-to-skin contact between the infant and mother (kangaroo care) is beneficial for infant health and facilitates maternal bonding. It is feasible and safe even when infants are supported by ventilators and infusions.
Feeding
Feeding should be by nasogastric tube until coordination of sucking, swallowing, and breathing is established at about 34 weeks gestation, at which time breastfeeding Breastfeeding (See also Nutrition in Infants.) Breast milk is the nutrition of choice for young infants. The American Academy of Pediatrics (AAP) recommends exclusive breastfeeding for a minimum of 6 months... read more is strongly encouraged. Most preterm infants tolerate breast milk, which provides immunologic and nutritional factors that are absent in cow’s milk formulas. However, breast milk does not provide sufficient calcium, phosphorus, and protein for very low-birthweight infants (ie, < 1500 g), for whom it should be mixed with a breast milk fortifier. Alternatively, specific preterm infant formulas that contain 20 to 24 kcal/oz (2.8 to 3.3 joules/mL) can be used.
In the initial 1 or 2 days, if adequate fluids and calories cannot be given by mouth or nasogastric tube because of the infant’s condition, IV parenteral nutrition with protein, glucose, and fats is given to prevent dehydration and undernutrition. Breast milk or preterm formula feeding via nasogastric tube can satisfactorily maintain caloric intake in small, sick, preterm infants, especially those with respiratory distress or recurrent apneic spells. Feedings are begun with small amounts (eg, 1 to 2 mL every 3 to 6 hours) to stimulate the gastrointestinal tract. When tolerated, the volume and concentration of feedings are slowly increased over 7 to 10 days. In very small or critically sick infants, total parenteral hyperalimentation via a peripheral IV or a percutaneously or surgically placed central catheter may be required for a prolonged period of time until full enteral feedings can be tolerated.
Hospital discharge
Preterm infants typically remain hospitalized until their medical problems are under satisfactory control and they are
Taking an adequate amount of milk without special assistance
Gaining weight steadily
Able to maintain a normal body temperature in a crib
Most preterm infants are ready to go home when they are at 35 to 37 weeks gestational age and weigh 2 to 2.5 kg. However, there is wide variation. Some infants are ready for discharge earlier and some require longer stays in the hospital. The length of time the infant stays in the hospital does not affect the long-term prognosis.
Preterm infants should be transitioned to the supine sleeping position before hospital discharge. Parents should be instructed to keep cribs free of fluffy materials including blankets, quilts, pillows, and stuffed toys, which have been associated with an increased risk of sudden unexplained infant death Sudden Unexpected Infant Death (SUID) and Sudden Infant Death Syndrome (SIDS) Sudden unexpected infant death (SUID) is a term used to describe any unexpected and sudden death in a child less than 1 year of age, which often occurs during sleep or in the infant's sleep... read more (SUID).
Because preterm infants are at risk of apnea, oxygen desaturation, and bradycardia while in a car seat, the American Academy of Pediatrics currently recommends that before discharge all preterm infants have their oxygen saturation monitored for 90 to 120 minutes while seated in the car seat that they will use after discharge. However, there are no agreed-upon criteria for passing or failing the test, and a recent report from the Canadian Paediatric Society (CPS) found that the car seat test had poor reproducibility and did not predict risk of mortality or neurodevelopmental delay. Thus, the CPS does not recommend routine testing before discharge (1 Evaluation reference An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ). Given the concerns about the car seat test, a common-sense approach to car travel is for a newly discharged preterm infant to be observed by a non-driving adult during all car seat travel until the infant has reached the due date and has remained consistently able to tolerate being in the car seat. Because the infant's color needs to be observed, travel should be limited to daylight hours. Long trips should be broken up into 45- to 60-minute segments so that the infant can be taken out of the car seat and repositioned.
Surveys show that most car seats are not installed optimally, so a check of the car seat by a certified car seat inspector is recommended. Inspection sites can be found here. Some hospitals offer an inspection service, but casual advice provided by an uncertified hospital staff member should not be considered equivalent to inspection by a certified car seat expert.
The American Academy of Pediatrics recommends that car seats be used only for vehicular transportation and not as an infant seat or bed at home.
After discharge, extremely preterm and very preterm infants should receive careful neurodevelopmental follow-up and appropriate early referral to intervention programs as needed for physical, occupational, and language therapy.
Prevention of Preterm Delivery
Although early and appropriate prenatal care is important overall, there is no good evidence that such care or any other interventions decrease the incidence of preterm birth.
The use of tocolytics to arrest preterm labor and provide time for prenatal administration of corticosteroids to hasten lung maturation is discussed elsewhere ( see Treatment Treatment Labor (contractions resulting in cervical change) that begins before 37 weeks gestation is considered preterm. Risk factors include prelabor rupture of membranes, uterine abnormalities, infection... read more ).
Key Points
There are many risk factors for preterm birth but they are not present in most cases.
Complications include hypothermia, hypoglycemia, respiratory distress syndrome, apneic episodes, intraventricular hemorrhage, developmental delay, sepsis, retinopathy of prematurity, hyperbilirubinemia, necrotizing enterocolitis, and poor feeding.
Mortality and likelihood of complications decrease greatly with increasing gestational age and birthweight.
Treat disorders and support body temperature and feeding.
Although women who have consistent prenatal care have a lower incidence of preterm birth, there is no evidence that improved prenatal care or other interventions decrease the incidence of preterm birth.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
National Highway Traffic Safety Administration: Child car seat inspection station locator
Late Preterm Infants
Complications of Late Preterm Infants
Although clinicians tend to focus on the more dramatic and obvious manifestations of problems of infants born < 34 weeks gestation, late preterm infants are at risk of many of the same disorders (see complications of preterm infants Complications An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ). Compared to term infants, they have longer hospital stays and higher incidence of readmission and diagnosed medical disorders. Most complications relate to dysfunction of immature organ systems and are similar to, but typically less severe than, those of infants born more prematurely. However, some complications of prematurity (eg, 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 , retinopathy of prematurity Retinopathy of Prematurity Retinopathy of prematurity is a bilateral disorder of abnormal retinal vascularization in premature infants, especially those of lowest birth weight. Outcomes range from normal vision to blindness... read more , bronchopulmonary dysplasia Bronchopulmonary Dysplasia (BPD) Bronchopulmonary dysplasia is chronic lung disease of the neonate that typically is caused by prolonged ventilation and is further defined by degree of prematurity and extent of supplemental... read more
, 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
) are uncommon in late preterm infants. In most cases, complications resolve completely.
Complications more common among preterm infants include the following:
Gastrointestinal tract: Poor feeding due to delayed maturation of the suck and swallow mechanism (primary reason for prolonged hospital stay and/or readmission)
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 : Caused by immature mechanisms for hepatic bilirubin metabolism and/or increased intestinal reabsorption of bilirubin (eg, if feeding difficulties cause decreased intestinal motility)
Temperature instability: Some degree of neonatal hypothermia Hypothermia in Neonates Hypothermia is defined by the World Health Organization as a core temperature < 36.5° C (97.7° F). In preterm infants, hypothermia increases morbidity and mortality. Hypothermia may be purely... read more in half of infants (caused by increased surface area to volume ratio, decreased adipose tissue, and ineffective thermogenesis from brown fat)
Evaluation of Late Preterm Infants
Routine screening for complications
There are variations in practice in the care of late preterm infants, particularly with respect to the gestational age and/or birthweight at which infants are routinely admitted to a NICU. Some hospitals routinely admit infants < 35 weeks gestation to the NICU, whereas others may have a cutoff of < 34 weeks. Still other hospitals have a discretionary approach. Regardless of the location of the infant, all late preterm infants need close monitoring of the following:
Temperature: There is a high risk of hypothermia, and some late preterm infants may need to be in an incubator. The infant's temperature should be routinely assessed. For infants who are in the mother's hospital room, the temperature of the room should be maintained at 22 to 25° C (72 to 77° F) similar to that recommended for newborn care areas.
Weight: Depending on the infant's intake, there may be excessive weight loss, dehydration, and hypernatremia. The infant should be weighed daily and the percent weight loss should be calculated and tracked. Electrolytes should be checked if the weight loss exceeds 10%.
Feedings and intake: Late preterm infants may breastfeed or bottle feed poorly and take insufficient amounts of milk. Nasogastric feeding assistance is commonly needed, particularly in infants who are 34 weeks gestation. Because the mother's milk may take 1 to 4 days to come in, supplementation with donor milk or formula may be necessary. The amount of milk that the infant receives as well as either the number of wet diapers or the urine output (calculated as mL/kg/hour) should be tracked.
Glucose: Early hypoglycemia (within the first 12 hours of life) is common, so early feeding and blood glucose screening as recommended by the American Academy of Pediatrics (1 Evaluation reference An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ) for the first 24 hours of life should be done. In addition, some experts recommend continued screening every 12 hours until discharge to detect infants with hypoglycemia due to insufficient milk intake.
Evaluation reference
1. Committee on Fetus and Newborn, Adamkin DH: Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics 127(3):575–579, 2011. doi: 10.1542/peds.2010-3851
Prognosis for Late Preterm Infants
Prognosis varies with presence and severity of complications. In general, mortality and the likelihood of complications decrease greatly with increasing gestational age and birthweight.
Respiratory issues typically resolve without long-term sequelae. Apneic episodes typically resolve by 37 to 38 weeks gestation and almost always by 43 weeks.
Neurodevelopmental disorders (see 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 ) are more common among late preterm infants (compared to full-term infants) assessed at 2 years of age and at kindergarten age (1 Prognosis reference An infant born before 37 weeks gestation is considered preterm. Prematurity is defined by the gestational age at which infants are born. Previously, any infant weighing < 2.5 kg was termed... read more ). Early identification by monitoring developmental milestones Developmental Milestones* and referring an intervention program for infants showing delays can be helpful.
Prognosis reference
1. McGowan JE, Alderdice FA, Holmes VA, Johnston L: Early childhood development of late-preterm infants: A systematic review. Pediatrics 127:1111–1124, 2011. doi: 10.1542/peds.2010-2257
Treatment of Late Preterm Infants
Supportive care
Specific treatment for complications
Identified disorders are treated. For infants without specific conditions, support is focused on body temperature and feeding.
Late preterm infants can be stressed by the metabolic demands of maintaining a normal core temperature of 36.5 to 37.5° C (97.7 to 99.5° F), which roughly corresponds to an axillary temperature of 36.5 to 37.3° C (97.7 to 99.1° F). The environmental temperature at which metabolic demands (and thus calorie expenditure) to maintain body temperature in the normal range are lowest is the thermoneutral temperature. A normal core temperature can be maintained at lower environmental temperatures at the cost of increased metabolic activity, so a normal core temperature is no assurance that the environmental temperature is adequate. Once the core temperature falls below normal, the environmental temperature is below what is called the thermoregulatory range and therefore far below the thermoneutral range. In clinical practice, a room with a temperature of 22.2 to 25.6° C (72 to 78° F) combined with skin-to-skin contact under blankets, swaddling with multiple blankets, and wearing a hat may provide a thermoneutral environment for a large and somewhat more mature late preterm infant. Smaller and less mature late preterm infants usually require an incubator for a period of time to provide a thermoneutral environment.
Breastfeeding Breastfeeding (See also Nutrition in Infants.) Breast milk is the nutrition of choice for young infants. The American Academy of Pediatrics (AAP) recommends exclusive breastfeeding for a minimum of 6 months... read more is strongly encouraged. Breast milk, which provides immunologic and nutritional factors that are absent in cow’s milk formulas, is well tolerated by preterm infants. If infants do not suck and/or swallow adequately, feedings should be given by nasogastric gavage beginning with small amounts and gradually increasing over time.
Key Points
Although late preterm infants (born between ≥ 34 weeks and < 36 6/7 weeks gestation) may appear to be similar in size and appearance to term infants, they are at increased risk of complications.
Complications include hypothermia, hypoglycemia, poor feeding, excessive weight loss, respiratory distress, hyperbilirubinemia, and an increased likelihood of readmission after discharge.
Treat disorders and support body temperature and feeding.
Monitor neurodevelopmental status and provide appropriate referral to address any disabilities.
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palivizumab |
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vitamin d |
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hydroxyprogesterone |
Makena |