Antenatal steroid | |
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Other names | Antenatal corticosteroids |
Specialty | OB/GYN |
Antenatal steroids, also known as antenatal corticosteroids, are medications administered to pregnant women expecting a preterm birth. When administered, these steroids accelerate the maturation of the fetus' lungs, which reduces the likelihood of infant respiratory distress syndrome and infant mortality. [1] The effectiveness of this corticosteroid treatment on humans was first demonstrated in 1972 by Sir Graham Liggins and Ross Howie, during a randomized control trial using betamethasone. [2]
Antenatal steroids have been shown to reduce the occurrence and mortality of infant respiratory distress syndrome, a life-threatening condition caused by underdeveloped lungs. [3]
Current evidence suggests that giving antenatal corticosteroids reduces risk of late miscarriages and baby deaths. The baby is also less likely to develop respiratory distress syndrome or die during or after birth. [1] They are also less likely to have intraventricular hemorrhage (bleeding of the brain), [4] [5] necrotizing enterocolitis (problems with the bowels), or systemic infections (infections affecting the whole body) in the first two days of life. [1]
Steroids do not appear to increase the number of women who develop infection of the fetal membranes (chorioamnionitis) or of the womb (endometritis). [1]
There is robust evidence that a single course of antenatal corticosteroids (i.e., 24 mg of betamethasone or dexamethasone), when there is a risk of preterm birth (at less than 34 weeks of gestation), reduces the risk of child death, regardless of resource level. [1] [6]
Further research must be conducted to adequately determine outcomes of antenatal steroid administration for multiple pregnancies. [1] However, certain national clinical practice guidelines recommend the usage of steroids for preterm birth regardless of multiple gestation. [7]
Antenatal steroids have also been shown to have definite beneficial effect in treating the condition of preterm premature rupture of membranes (PPROM). [8] Similar to its effects on preterm birth, research evidence suggests that the administration of antenatal steroids to patients with PPROM reduces risks of neonatal mortality, intraventricular hemorrhage and respiratory distress syndrome. [9]
Preliminary research has suggested that the use of antenatal corticosteroids may have adverse long-term effects. [10] In animals, antenatal corticosteroid use has been associated with adverse effects on the cardiometabolic system and inhibited growth of the brain, as well as worsened memory and learning difficulties. [10] While it is not yet certain if human fetuses would experience these same effects, some literature has found that human preterm fetuses treated with antenatal corticosteroids may be at greater risk of developing mental and behavioural disorders during childhood, [11] as these drugs are able to enter the fetus' brain and could affect neurodevelopment. [10] In both humans and animals, research has suggested that repeated doses of antenatal corticosteroids could lead to an increased risk of vision and hearing issues in the long-term. [12] [13] [14]
Contraindications to the administration of antenatal corticosteroids include: [15]
Corticosteroids encourage the development of the lungs in a premature fetus before birth, [16] and are administered when the premature fetus is expected to be delivered within 24 to 48 hours. The period of optimal benefit begins 24 hours after administration and lasts 7 days. [17] [18] In some parts of the world, antenatal steroids are used at up to 36 weeks of pregnancy. [19] The time between administration of steroids and delivery may alter the effectiveness of the steroids. [20]
Country | Organization (Year of Publication) | Gestational Age Recommendations | Other Inclusion Criteria | Betamethasone or Dexamethasone |
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Australia & New Zealand | Australian & New Zealand Neonatal Network (2018) [21] | < 34 weeks and 6 days | Preterm birth anticipated in 1 – 8 days | Not specified |
Antenatal Corticosteroids Clinical Practice Guidelines Panel (2015) [22] | ≤ 34 weeks and 6 days | Preterm birth anticipated in ≥7 days | Either Betamethasone or Dexamethasone | |
Society of Obstetric Medicine of Australia and New Zealand (2014) [23] | < 34 weeks | - | Not specified | |
Canada | Society of Obstetricians & Gynaecologists of Canada (2018) [24] | 24 – 34 weeks and 6 days | Preterm birth anticipated in ≥7 days | Either Betamethasone or Dexamethasone |
United Kingdom | Royal College of Obstetricians and Gynaecologists (2015) [25] | 24 – 33 weeks and 6 days | Anticipated preterm birth | Not specified |
United States of America | The American College of Obstetricians and Gynecologists (2020) [7] | 24 – 33 weeks and 6 days | Preterm birth anticipated within 7 days | Betamethasone |
International | World Health Organization (2015) [26] | 24 – 34 weeks | Gestational age can be accurately assessed, preterm birth anticipated within 7 days, lack of maternal infection | Either Betamethasone or Dexamethasone |
Common corticosteroids include dexamethasone and betamethasone. Dexamethasone is often recommend over the latter due to its increased efficacy and safety, wide availability, and low cost, [27] while betamethasone is better at preventing the softening of the brain in premature fetuses. [28] Both drugs share certain commonalities, including the ability to traverse the placenta, as well as a very similar molecular structure. In fact, the two steroids are identical save for a single additional methyl group on betamethasone. [29] Although betamethasone has an increased half-life, there is no significant evidence indicating that one might be better than the other. [7] Literature on the subject is limited and inconsistent. [7] A Cochrane review (2022) found that it was unclear if there were significant differences, [30] while other studies determined that betamethasone results in improved longer term outcomes. [31]
In order to generate improved respiratory outcomes, antenatal steroids act on cells called type II pneumocytes which are located within the alveoli of infant lungs. [32] Glucocorticoids both increase rates of cell maturation, as well as increase the production of mRNA coding for proteins required for the synthesis of surfactant. [32] Surfactant is a phospholipid-rich substance secreted by the lungs in order to increase elasticity and decrease surface tension, consequently generating more efficient rates of ventilation. [33] Additionally, surfactant lines the insides of alveoli in the lungs and as a result, prevents alveoli from collapsing during exhalation. [34] Since infants born preterm often have immature or incompletely developed lungs, the surfactant coating of the alveoli is similarly insufficient, resulting in poor respiratory outcomes or the development of respiratory distress syndrome. [35] The administration of antenatal corticosteroids increases production of surfactant (decreasing the need to use surfactant after birth), and therefore result in better health outcomes for preterm infants. [1]
In 1969, Graham Liggins, a medical research scientist, began investigating the effects of dexamethasone administration on the timing of labor in pregnant sheep. [36] Liggins conducted this experiment in the hopes of proving his hypothesis that the fetus, and not the mother, is responsible for inducing labour. [37] Liggins found that dexamethasone caused pregnant sheep to deliver their fetuses prematurely, however, despite the fact that the lamb fetus was extremely premature, it was delivered alive. [37]
With the help of his colleague, pediatrician Ross Howie, Liggins conducted a similar experiment with 282 human women, all of whom were projected to have a preterm delivery. [38] This preliminary trial showed that the administration of corticosteroids, specifically betamethasone, resulted in immediate improvements that were statistically significant, such as: [38]
These findings were first reported in the article A Controlled Trial of Antepartum Glucocorticoid Treatment for Prevention of the Respiratory Distress Syndrome in Premature Infants, published in the journal Pediatrics in 1972. [38] Liggins and Howie's research proved that antenatal corticosteroids were able to decrease respiratory complications and infant mortality by inducing cellular differentiation, and thus maturation, in the lungs. [37] [38] However, these results were not incorporated into clinical practice in the United States until over two decades later. [37]
Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF) and have meconium within their lungs. Therefore, MAS has a wide range of severity depending on what conditions and complications develop after parturition. Furthermore, the pathophysiology of MAS is multifactorial and extremely complex which is why it is the leading cause of morbidity and mortality in term infants.
Intrauterine growth restriction (IUGR), or fetal growth restriction, is the poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infant's birth weight percentile. The causes of IUGR are broad and may involve maternal, fetal, or placental complications.
Dexamethasone is a glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive lung disease, croup, brain swelling, eye pain following eye surgery, superior vena cava syndrome, and along with antibiotics in tuberculosis. In adrenocortical insufficiency, it may be used in combination with a mineralocorticoid medication such as fludrocortisone. In preterm labor, it may be used to improve outcomes in the baby. It may be given by mouth, as an injection into a muscle, as an injection into a vein, as a topical cream or ointment for the skin or as a topical ophthalmic solution to the eye. The effects of dexamethasone are frequently seen within a day and last for about three days.
Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 28 and 32 weeks, early preterm birth occurs between 32 and 34 weeks, late preterm birth is between 34 and 36 weeks' gestation. These babies are also known as premature babies or colloquially preemies or premmies. Symptoms of preterm labor include uterine contractions which occur more often than every ten minutes and/or the leaking of fluid from the vagina before 37 weeks. Premature infants are at greater risk for cerebral palsy, delays in development, hearing problems and problems with their vision. The earlier a baby is born, the greater these risks will be.
Fetal distress, also known as non-reassuring fetal status, is a condition during pregnancy or labor in which the fetus shows signs of inadequate oxygenation. Due to its imprecision, the term "fetal distress" has fallen out of use in American obstetrics. The term "non-reassuring fetal status" has largely replaced it. It is characterized by changes in fetal movement, growth, heart rate, and presence of meconium stained fluid.
Infant respiratory distress syndrome (IRDS), also called respiratory distress syndrome of newborn, or increasingly surfactant deficiency disorder (SDD), and previously called hyaline membrane disease (HMD), is a syndrome in premature infants caused by developmental insufficiency of pulmonary surfactant production and structural immaturity in the lungs. It can also be a consequence of neonatal infection and can result from a genetic problem with the production of surfactant-associated proteins.
Transient tachypnea of the newborn is a respiratory problem that can be seen in the newborn shortly after delivery. It is caused by retained fetal lung fluid due to impaired clearance mechanisms. It is the most common cause of respiratory distress in term neonates. It consists of a period of tachypnea (rapid breathing. Usually, this condition resolves over 24–72 hours. Treatment is supportive and may include supplemental oxygen and antibiotics. The chest x-ray shows hyperinflation of the lungs including prominent pulmonary vascular markings, flattening of the diaphragm, and fluid in the horizontal fissure of the right lung.
Tocolytics are medications used to suppress premature labor. Preterm birth accounts for 70% of neonatal deaths. Therefore, tocolytic therapy is provided when delivery would result in premature birth, postponing delivery long enough for the administration of glucocorticoids, which accelerate fetal lung maturity but may require one to two days to take effect.
Fetal viability is the ability of a human fetus to survive outside the uterus. Medical viability is generally considered to be between 23 and 24 weeks gestational age. Viability depends upon factors such as birth weight, gestational age, and the availability of advanced medical care. In low-income countries, half of newborns born at or below 32 weeks gestational age died due to a lack of medical access; in high-income countries, the vast majority of newborns born above 24 weeks gestational age survive.
Betamethasone is a steroid medication. It is used for a number of diseases including rheumatic disorders such as rheumatoid arthritis and systemic lupus erythematosus, skin diseases such as dermatitis and psoriasis, allergic conditions such as asthma and angioedema, preterm labor to speed the development of the baby's lungs, Crohn's disease, cancers such as leukemia, and along with fludrocortisone for adrenocortical insufficiency, among others. It can be taken by mouth, injected into a muscle, or applied to the skin, typically in cream, lotion, or liquid forms.
Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, is breakage of the amniotic sac before the onset of labor. Women usually experience a painless gush or a steady leakage of fluid from the vagina. Complications in the baby may include premature birth, cord compression, and infection. Complications in the mother may include placental abruption and postpartum endometritis.
Bronchopulmonary dysplasia is a chronic lung disease which affects premature infants. Premature (preterm) infants who require treatment with supplemental oxygen or require long-term oxygen are at a higher risk. The alveoli that are present tend to not be mature enough to function normally. It is also more common in infants with low birth weight (LBW) and those who receive prolonged mechanical ventilation to treat respiratory distress syndrome. It results in significant morbidity and mortality. The definition of bronchopulmonary dysplasia has continued to evolve primarily due to changes in the population, such as more survivors at earlier gestational ages, and improved neonatal management including surfactant, antenatal glucocorticoid therapy, and less aggressive mechanical ventilation.
Perinatal mortality (PNM) is the death of a fetus or neonate and is the basis to calculate the perinatal mortality rate. Perinatal means "relating to the period starting a few weeks before birth and including the birth and a few weeks after birth."
Maternal–fetal medicine (MFM), also known as perinatology, is a branch of medicine that focuses on managing health concerns of the mother and fetus prior to, during, and shortly after pregnancy.
Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or small size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that interfere with normal development of the lungs. Primary (idiopathic) pulmonary hypoplasia is rare and usually not associated with other maternal or fetal abnormalities.
The lecithin–sphingomyelin ratio is a test of fetal amniotic fluid to assess for fetal lung immaturity. Lungs require surfactant, a soap-like substance, to lower the surface pressure of the alveoli in the lungs. This is especially important for premature babies trying to expand their lungs after birth. Surfactant is a mixture of lipids, proteins, and glycoproteins, lecithin and sphingomyelin being two of them. Lecithin makes the surfactant mixture more effective.
Surfactant therapy is the medical administration of exogenous surfactant. Surfactants used in this manner are typically instilled directly into the trachea. When a baby comes out of the womb and the lungs are not developed yet, they require administration of surfactant in order to process oxygen and survive. This condition that the baby has is called newborn respiratory distress syndrome, and it is treatable. Surfactant coat the smallest parts of the lungs called the alveoli and helps for oxygen to go in and for carbon dioxide to go out. How surfactant does this is by not allowing the alveoli to collapse and to retain their inflated shape when the baby exhales.
Henrik Verder is a pediatrician and the inventor of the INSURE and LISA methods combined with nasal CPAP. In 1989 he used this pioneering method to successfully treat the first premature infant with severe RDS. Verder is a significant researcher within the field of paediatrics, with more than 50 publications and over 500 citations.
Christian P. Speer is a German pediatrician and Professor of Pediatrics specialized in neonatology at the Julius Maximilian University of Würzburg. Speer is known for his scientific and educational contributions in neonatal medicine.
Henry Lewis Halliday was a British-Irish peaditrician and neonatologist. In 2021, Halliday was awarded the James Spence Medal for research into neonatology, for coordinating two of the largest neonatal multicentre trials for prevention and treatment of a number of neonatal respiratory illnesses and for a breakthrough in the development of a new lung surfactant that brought relief to very small babies suffering from infant respiratory distress syndrome (RDS).