Methotrexate is given weekly as an intramuscular injection of 15 to 25 mg. Side effects are rare and include leukopenia and hypersensitivity interstitial pneumonitis. Hepatic fibrosis is the most severe potential sequela of long-term therapy. Patients with concomitant alcohol abuse and/or morbid obesity are more likely to develop hepatic fibrosis and therefore should not be treated with methotrexate. It is prudent to obtain a baseline chest radiograph and to monitor complete blood count, liver function and renal function every two weeks until the patient is receiving oral therapy, and every one to three months thereafter. Before methotrexate therapy is initiated, the risks of treatment and the possible need for a liver biopsy should be discussed with the patient.
Recent data also suggest that betamethasone can be beneficial in pregnant women at high risk of late preterm birth, between 34 0/7 weeks and 36 6/7 weeks of gestation who have not received a prior course of antenatal corticosteroids. The Maternal Fetal Medicine Units (MFMU) Network Antenatal Late Preterm Steroids trial ( 24 ) was a double-blind, placebo-controlled, randomized clinical trial designed to evaluate the use of antenatal betamethasone for pregnant women at high risk of delivery in the late preterm period. Women were identified to be at high risk if they presented in preterm labor, had preterm PROM, or if they had a planned delivery in the late preterm period, with the indication at the discretion of the obstetrician–gynecologist or other health care provider. Tocolysis was not employed as a part of this trial, and delivery was not delayed for obstetric or medical indications. The study found that the administration of betamethasone led to a significant decrease in the primary outcome, which was the need for respiratory support. A larger decrease was demonstrated for severe respiratory complications, from % in the placebo group to % in the betamethasone group (RR, ; 95% CI, –; P <.001). There were also significant decreases in the rates of transient tachypnea of the newborn; bronchopulmonary dysplasia; a composite of respiratory distress syndrome (RDS), transient tachypnea of the newborn and RDS; and the need for postnatal surfactant. Infants exposed to betamethasone were less likely to require immediate postnatal resuscitation. There was no increase in proven neonatal sepsis, chorioamnionitis, or endometritis with late preterm betamethasone. Hypoglycemia was more common in the infants exposed to betamethasone % versus % (RR, ; 95% CI, –); however, there were no reported adverse events related to hypoglycemia, which was not associated with an increased length of hospital stay. The rates of hypoglycemia found in the trial are similar to what is reported in the general population of late preterm infants ( 25 ). Although not studied in this trial, long-term adverse outcomes of prolonged and persistent neonatal hypoglycemia have been described ( 26 , 27 ). In order to reduce this risk and achieve the benefits of betamethasone therapy for fetal maturity in late preterm pregnancies, the American Academy of Pediatrics’ guidelines should be followed when employing this therapy (27). The American Academy of Pediatrics recommends the monitoring of neonatal blood sugars for late preterm infants because late preterm birth is a known risk factor for hypoglycemia. A single course of betamethasone is recommended for pregnant women between 34 0/7 weeks and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids (24, 28 ).