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Defined as birth prior to 37 weeks gestation
Preterm birth is the most common cause of infant mortality, causing almost 30 percent of neonatal deaths.
In infants with extremely low birthweight additional parenteral amino acids in the first five days after birth does not result in a higher rate of survival without neurodisability at age 2.
The racial disparity in infant mortality in the US is driven primarily by very preterm birth:suggesting the quality of care and treatment offered differ among neonatal intensive care units by race and ethnicity.
The prevalence and severity of preterm birth is likely to worsen with increasing temperatures and exacerbate racial disparities in preterm birth rates.
The leading cause of perinatal morbidity and death and the rate of pre-term birth has not decreased over the past 20 years.
Rate is about 10%.
It is the most important cause of morbidity and mortality in children younger than five years.
It is an important risk factor for psychiatric, metabolic, cardiovascular and renal disease later in life.
Evidence exists that being born in the late preterm period, between 34 and 36 weeks gestation is associated with long-term adverse effects.
Previable birth between 22 weeks to 25 weeks six days gestation occurs in 0.4% of all deliveries in the US (in 2015), but accounted for about 40% of all neonatal deaths.
For infants born before 28 weeks of gestation there are one more major impairments including cerebral palsy, intellectual disability, deafness, or blindness in approximately 40% of infants.
Survival rates at the lowest gestational ages continues to increase, but that is supporting whether interventions improve neonatal outcomes or mobilities is limited.
Long-term neurodevelopmental impairment among infants born at the lowest gestational ages is common and survival rates remain low: survival in a population born at 22 to 24 weeks is 36% and survival without neurodevelopmental impairment is 20%.
In infants born before 29 weeks gestation docosahexaenoic acid supplementation given to prevent bronchopulmonary dysplasia is associated with a modestly higher intelligence score at five years than control feeding: infants born before 29 weeks gestation do not receive a normal supply of DHA.
In 2019, 66% of perivable neonates were born to a mother who identified as either Black or Hispanic.
Adverse outcomes include cerebral palsy, increased hospital admissions in early childhood, lower childhood height, asthma, long-term illnesses, and poorer educational attainment.
Improvement in management of prenatal care has resulted in almost universal survival of greater than 97% among preterm births.
In a study of 10,877 infants born at a gestational age of 22 to 28 weeks (extreme prematurity) and two year outcomes of 2566 infants with gestational age of 22 to 26 weeks found: survival among extremely preterm infants increased over time reaching greater than 78% among surviving infants, 21% born at 22 to 26 weeks of gestation age experience severe neurodevelopmental impairment at two years of age.
Long-term follow-up studies show a higher risk of behavioral disorders such as attention deficit disorder, autism, and psychiatric disorders among children born preterm than among those born at term.
An estimated 4-5% of infants are born at 34-36 weeks, and 30% of preterm births follow premature rupture of the membranes.
Subclinical hypothyroidism, and anti-thyroid peroxidase antibody levels in pregnant women are risk factors for preterm birth.
Cannabis use is associated with a 12% preterm birth rate, while it is is 6.1% among non-users.
Maternal antenatal corticosteroid treatment to accelerate fetal maturation is standard care before 34 weeks gestation when there is a risk of delivery within seven days.
In infants born before 34 weeks corticosteroids reduces the risk of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, need for mechanical ventilation, systemic infections, and death.
In a study of 670,097 children exposed to maternal antenatal corticosteroid treatment was associated with significant mental and behavioral disorders in children (Raikkonen K).
7-10% of all pregnancies and account for a major amount of infant morbidity and mortality.
Preterm birth infants are at higher risk for short term and long term respiratory, infectious, metabolic, and neurologic conditions with higher risks among those born during the early preterm.
The pre-term birth rate is 5-9% in most European countries.
Affects 1 in 9 live births in the US, and 1 in 5 live births among Black Americans.
Approximately 75,000 infants classified as very preterm gestational age less than 32 weeks in 2011.
Approximately 200,000 infants annually admitted to a neonatal ICU for treatment of prematurity.
Annual costs greater than $26 billion.
More than 95% of preterm infants in developed countries survive into adulthood.
The leading cause of perinatal morbidity and death and the rate of pre-term birth hanot decreased over the past 20 years.
Leading cause of infant mortality in the industrialized world after congenital anomalies.
Complications from preterm births accounts for about two thirds of US infant deaths.
Most common cause of neonatal morbidity and mortality in the world.
Preterm birth has been associated with increased relative risks of cardiometabolic, respiratory, and neuropsychiatric disorders in adulthood.
In a Swedish study of persons born prematurely resulted in 54.6% being alive with no major comorbidities at adulthood(Crump C).
11% of singleton births occur before 37 weeks in the U.S.
Also most 75% of perinatal deaths occur in infants born before 37 weeks gestation
Thrombocytopenia is common in preterm neonates, and at some point during their stay in a neonatal intensive care unit, this condition affects up to 73% of patients with the birthweight of less than 1000 g.
The smallest and most premature infants have the highest incidence of bleeding, approximately 30% of neonates born with a weight of less than 1500 g, and intracranial hemorrhage develops usually in the first week of life.
Because of high rates of thrombocytopenia and bleeding in this population preterm infants receive platelet transfusions at a higher platelet count threshold than those used in older children and adults.
13% of infants born in the U.S. are born before they reach 37 weeks (Society for Maternal Fetal Medicine).
Late preterm birth rate higher in the U.S. than in other developed nations.
Rate of late preterm births, especially between 34 and 36 weeks, has increased from 6.8% of births in 1990 to 8.1% in 2006.
The largest increases in preterm births has occurred at 36 weeks.
Small decline in preterm births over the past 5 years, but rates in the US remain about 30% higher than in the 1980’s.
Prevalence has increased probably because of multiple gestation, obstetrics interventions, and ultrasound-based estimates of gestational age.
Cause is unknown in over half of the cases.
Infants born before 32 weeks represent more than 2% of all live births with survival rates exceeding 85%.
Very preterm infants have higher mortality and morbidity than term infants, partly because they are prone to respiratory failure and often require mechanical ventilation through an endotracheal tube after birth.
Following extubation continuous positive pressure airway or high flow nasal cannulae are have similar respiratory support levels.
High-flow nasal cannulae can deliver heated and humidified oxygen at flowrates of more than 1 L per minute through small nasal prongs., is easy to use and is more comfortable for the infant while allowing mother infant bonding compared to CPAP.
5-15% of surviving infants develop cerebral palsy, severe neurosensory abnormalities or both.
Disability occurs in 60% of survivors born at 26 weeks and in 30% of those born at 31 weeks.
25-50% of children develop impaired cognitive, behavioral and social problems.
After excluding earlier deaths, low gestational age at delivery associated with increased mortality in early childhood and young adulthood (Crump C et al).
Up to 30% associated with premature rupture of the membranes.
Results in 75-90% of all neonatal deaths not due to lethal congenital malformation, and 50% of childhood neurological disabilities, including cerebral palsy, blindness, and deafness.
Babies born at 22-32 weeks of gestation have a higher risk of mortality from the perinatal period through 5 years of age (Swamy), compared to term infants.
Most common cause of death in premature infants is infections and is a major threat for poor outcomes.
Late onset sepsis is mainly due to nosocomial infections in the perinatal period and effects 21% of very low birth weight, neonates.
Late onset, greater than 72 hours of age, blood stream infections in a very low birth weight infants is complicated by high mortality and neuro- developmental impairment.
Linked to preterm birth to insulin resistance. Type 2 diabetes in childhood, young adulthood, and middle adulthood.
There is an inverse association between gestational age and elevated plasma insulin levels and in early childhood
Over the nearly 65,000 low birth weight infants born each year approximately 13,000 infections, 2300 deaths, and neuro- developmental impairment occurs in 3000 survivors.
Among infants of extremely low birth weight less than 1000 g, neuro- developmental impairment occurs in 45% in those who survive bacteremia and 57% in those who survive fungal sepsis (Stoll).
In very low birth weight neonates the digestive tract is a major site for colonization and translocation of pathogens.
Highest mortality rates occur at delivery and at the shortest gestations.
In comparison with term infants preterm infants have lower education levels and the lower the gestational age, the lower the average educational attainment.
Preterm and very low birthweight intense have significant motor impairment which persists throughout childhood (Kievet, JF).
In a study, developmental outcome of children aged 10 years was compared with assessment of children aged 2 years for surviving children of an initial cohort of infants born at fewer than 28 weeks’ gestation.
67% of children showed no change in level of neurodevelopmental assessment, 27% showed improvement, and 5% showed worsening.
63% of the children with moderate to severe neurodevelopmental impairment at 2 years of age and 36% of the children with profound neurodevelopmental impairment at 2 years of age had mild or no impairment at 10 years of age.
Findings strongly support the plasticity of the central nervous system in these children and their ability to improve neurodevelopmental outcomes even in the most profoundly affected neonates born extremely premature.
Encouraging early and aggressive developmental intervention and offering hope to parents or guardians, including among the earliest and most severely affected preterm neonates.
Very preterm infants from 22-32 weeks have less ability to reproduce when they become adults.
Women adults born as a preterm infant have an increased risk of having a preterm infant compared with women who were born at term.
More than half of all preterm deliveries occur in apparently low-risk pregnancies, with no known risk factors.
Periodontitis, an inflammatory process caused mainly by gram negative bacteria that destroy tooth supporting connective tissue and bone, associated with increased risk of preterm birth, low birth weight and preeclampsia.
Treatment of periodontitis in pregnancy improves dental health but does not alter rates of preterm birth, low birth weight or fetal growth restriction.
Respiratory distress syndrome affects 40-50% of infants delivered before 32 weeks of gestation.
More than one third of survivors with a birth weight of less than 1250 g have bronchopulmonary dysplasia (chronic lung disease of prematurity) defined as a need for supplemental oxygen.
In a randomized trial comparing target ranges of oxygen saturation of 85-89% or 91-95% among 316 infants born between born between 24 weeks 0 days and 27 weeks 6 days of gestation: the lower target range did not signficantly decrease composite outcome of severe retinopathy or death, but did increase mortality and a significant decrease in severe retionopathy among survivors (SUPPORT STUDY GROUP).
Incidence of retinopathy of prematurity inceased with exposure to unrestricted oxygen therapy in preterm infants.
The practice of restricting the fraction of inspired oxygen to 0.5 or less results in an excess of 16 deaths per case of blindness prevented (Bolton DP).
Data suggest levels of oxygen saturation previously felt to be at the upper end of the normal range may increase the risk of retinopathy compared with levels at the lower range of normal (Tin W, Chow,LC Anderson CG).
Infants have high losses of heat and insensible water loss related to the large ratio of surface area to body weight.
Extreme preterm infants may have insensible water losses of greater than 100 cc/kg/day related to immature skin, lack of subcutaneous tissue and large exposed surface area.
By 2 weeks of life there is a rapid maturation of the epidermis.
Respiratory distress syndrome and intraventricular hemorrhage account for a significant proportion of neonatal deaths.
Preterm infants frequently treated with surfactant for respiratory distress syndrome, and it is usually administered via endotracheal tube during mechanical ventilation.
The application of surfactant to spontaneously breathing preterm infants receiving positive airway pressure, reduces the need for mechanical ventilation (Gopel W, et al).
Chronic lung disease the primary long-term pulmonary complication that is associated with pulmonary hypertension and abnormalities of alveolarization and neovascularization.
Protein delivery of 1.5 g per kilogram per day soon after birth for preterm infants is necessary to maintain a positive protein balance.
Current recommendations is the target early protein delivery of 2 1/2 to 3.5 g per kilogram per day of proteins.
Protein is one of several components of several macronutrients and numerous micronutrients that nourish growing preterm infants
Most medications administered to preterm infants lack safety data and more than 90% not approved by FDA.
No agents have substantially improved outcomes of preterm infants since introduction of antenatal corticosteroids and surfactant.
Early administration of dexamethasone had no effect of death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.
Antenatal corticosteroids use 24 hours to seven days before birth to women in preterm labor at less than 34 weeks gestation is associated with improved lung maturity, a substantial reduction in the risk of respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis and neonatal death (Roberts D, Dalziel S).
Antenatal corticosteroids in a meta-analyses did not improve outcomes when utilized in less than 26 weeks’ gestation (Roberts D, Onland W et al).
A single course of antenatal corticosteroids reduces the risk of long-term neurologic sequelae.
The use of antenatal corticosteroids before 24 weeks gestation is not recommended, however in a prospective study of infants with birth weight between 401 g and 1000 g born at 22-25 weeks’ gestation demonstrated infants born at 23-25 weeks’ gestation, antenatal exposure to corticosteroids was associated with a lower rate of death or neurodevelopmental impairment at 18 to 22 months (Carlo WA et al).
In the Ante-natal Late Preterm Steroid trial, there was a 20% relative reduction in the primary outcome, respiratory morbidity, but the absolute reduction in the primary outcome was only 2.8%.
The effective antenatal corticosteroids was essentially limited to a reduction in the transit tachypnea of the newborn with no discernible benefit on mortality, respiratory distress syndrome, necrotizing enterocolitis, or intraventricular hemorrhage.
In the study corticosteroids was associated with a 40% increase in neonatal hypoglycemia.
Infants exposed to corticosteroids and born more than 7 days after exposure to a single course of antenatal corticosteroids have a lowered birthweight and increased perinatal mortality compared the unexposed infants.
Observational studies suggest exposure to repeat courses of corticosteroids associated with poor infant growth, delayed psychomotor development and abnormal childhood behavior compared with exposure to a single course of such drugs.
Not all observational studies have shown increased neurosensory disabilities after repeated doses of corticosteroids in utero, and one study suggested a reduction in the incidence of cerebral palsy.
Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) indicated babies of women that repeated doses of corticosteroids compared to those given a single course had less respiratory distress syndrome (33% vs. 41%), severe neonatal lung involvement (12% vs. 20%) and other serious morbidity (20% vs. 26%).
Magnesium infusions for individuals at high risk for prematurity at 30 to 34 weeks gestation is not associated with a reduction in a primary outcome of death or cerebral palsy in children at two years (Crowther CA).
Correlation between cervical length and risk of preterm births.
A cervical length of <3 cm before 16 weeks gestations is associated strongly with preterm birth.
Shortened cervical length of less than 25 mm as measured by transvaginal sonography in the second trimester correlates with the risk of preterm delivery and occurs in approximately 1 to 2.5% of the population.
Cervical pessary with a single gestation, and a cervical length of 20 mm or less, does not decrease the risk of preterm birth, and is associated with a higher rate of fetal or neonatal/infant mortality.
Associated with infection of the upper genital tract.
Systemic fungal diseases caused mainly by candida species is a complication of such neonates.
Candida species colonize patients to 60% of very low birth weigh neonates during the first months in the neonatal ICU with up to 20% of such infants progressing to invasive fungal infection.
For patients who have had a prior spontaneous preterm birth and a current singleton pregnancy, progesterone therapy may prevent a subsequent preterm delivery.
Small size at term birth and during infancy associated with increased risk of impaired glucose metabolism and cardiovascular disease later in life.
Fungal infections in such patients associated with an increase in the rate of death from all causes to 28% compared to 7% for infants without such infection.
Early diagnosis and treatment of systemic fungal infections does not prevent prolonged hospitalization, high costs of car or neurodevelopmental impairments.
Very low weight birth babies are at risk for invasive fungal infections because of an immature immune system and the requirement for invasive supportive medical procedures.
The risk of severe medical disabilities increased sharply with decreasing gestational age at birth.
Associated with impaired motor, cognitive behavioral psychological and social function among preschool and school age children.
Associated with autism spectrum disorders.
The USPSTF opposes screening for bacterial vaginosis in pregnant persons not at increased risk for preterm delivery.
Inguinal hernia is the most common congenital abnormality in preterm infants requiring surgery.
The incidence of inguinal hernia increases as gestational age decreases, reaching 40% in males born at 24 weeks gestation.
Treatment is operative repair to prevent inguinal hernia incarceration.
Delaying inguinal hernia repair surgery until after initial discharge from the neonatal intensive care unit resulted in fewer infants having adverse events.
Mother’s milk, feeding in the NICU, predicts improved neurological development and outcomes through school-age.
A trial of nutrition interventions to support moderate to late preterm infants until full nutrition with mothers breast milk was possible, but did not show any effects on the time to full enteral feeding or on body composition at four months of corrected gestational age (DIAMOND trial group).