Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial

Murphy, Kellie; Hannah, Mary E.; Willan, Andrew R.; Hewson, Sheila; Ohlsson, Arne; Kelly, Edmond; Matthews, Stephen G.; Saigal, Saroj; Asztalos, Elizabeth; Ross, Susan; Delisle, Marie-France; Amankwah, Kofi; Guselle, Patricia; Gafni, Amiram; Lee, Shoo K.; Armson, B. Anthony

doi:10.1016/s0140-6736(08)61929-7

Cited by 330 publications

(233 citation statements)

References 21 publications

Supporting

Mentioning

218

Contrasting

Unclassified

Order By: Relevance

“…Most clinical trials suggest that sustained exposure or repeated doses of corticosteroids are more effective in improving foetal outcomes (Abbasi et al 2000, Crowther et al 2006, Murphy et al 2008, Asztalos et al 2010. However, there is also a considerable body of evidence to suggest that multiple dosing does not carry any additional respiratory or cardiovascular benefits for the infant and is more detrimental for foetal growth and postnatal neurodevelopment, as well as adrenal function, compared with a single dose (Banks et al 1999, Spinillo et al 2004, Nair & Omar 2009, Bontis et al 2011, Murphy et al 2012.…”

Section: Implications and Concluding Remarksmentioning

confidence: 99%

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Rog-Zielinska¹,

Richardson²,

Denvir³

et al. 2013

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Glucocorticoids are steroid hormones, essential in mammals to prepare for life after birth. Blood levels of glucocorticoids (cortisol in most mammals including humans; corticosterone in rats and mice) rise dramatically shortly before birth. This is mimicked clinically in the routine administration of synthetic glucocorticoids to pregnant women threatened by a preterm birth or to preterm infants to improve neonatal survival. Whilst effects on lung are well documented and essential for postnatal survival, those on heart are less well known. In this study, we review recent evidence for a crucial role of glucocorticoids in late gestational heart maturation. Either insufficient or excessive glucocorticoid exposure before birth may alter the normal glucocorticoid-regulated trajectory of heart maturation with potential life-long consequences.

show abstract

Section: Implications and Concluding Remarksmentioning

confidence: 99%

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Rog-Zielinska¹,

Richardson²,

Denvir³

et al. 2013

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…The major concerns are for adverse effects on fetal growth and neurodevelopment. In MACS-5, children who were exposed to multiple courses of ACS in utero had reduced weight, length, and head circumference at birth [4], and those who were born at term had an almost 4-fold increased risk of neurosensory difficulties at 5 years of age [9, 10]. …”

Section: Discussionmentioning

confidence: 99%

“…A current Cochrane review by Crowther et al [3] suggests that weekly courses of ACS (vs. a single course) are associated with the reduced occurrence and severity of neonatal lung disease and serious infant morbidities, without any evidence of harm at 2-year follow up, although without outcome benefits at that age. In the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study at 5 Years of Age (MACS-5), multiple ACS courses did not improve preterm birth outcomes with regard to perinatal or neonatal morbidity and mortality, and were associated with decreased weight, length, and head circumference at birth [4]. The need to further investigate these clinical observations is supported by a large number of animal studies where repeated exposure to ACS was associated with reduced fetal growth, adverse effects on brain development, and delayed myelination [5-7].…”

Section: Introductionmentioning

confidence: 99%

Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep

Rittenschober-Böhm

Rodger²,

Jobe

et al. 2018

Neonatology

View full text Add to dashboard Cite

Background: Antenatal corticosteroids (ACS) improve preterm neonatal outcomes. However, uncertainty remains regarding the safety of ACS exposure for the developing fetus, particularly its neurosensory development. Objectives: We investigated the effect of single and multiple ACS exposures on auditory nerve development in an ovine model of pregnancy. Methods: Ewes with a single fetus (gestational age [GA] 100 days) received an intramuscular injection of 150 mg medroxyprogesterone-acetate, followed by intramuscular (i) betamethasone (0.5 mg/kg) on days 104, 111, and 118 GA; (ii) betamethasone on day 104 and saline on days 111 and 118 GA; or (iii) saline on days 104, 111, and 118 GA, with delivery on day 125 GA. Transmission electron microscope images of lamb auditory nerve preparations were digitally analyzed to determine auditory nerve morphology and myelination. Results: Relative to the control, mean auditory nerve myelin area was significantly increased in the multiple-treatment group (p < 0.001), but not in the single-treatment group. Increased myelin thickness was significantly changed only in a subgroup analysis for those axons with myelin thickness greater than the median value (p < 0.001). Morphological assessments showed that the increased myelin area was due to an increased likelihood of decompacted areas (p = 0.005; OR = 2.14, 95% CI 1.26–3.63; 31.6 vs. 18.2% in controls) and irregular myelin deposition (p = 0.001; OR = 5.91, 95% CI 2.16–16.19; 49.0 vs. 16.8% in controls) in the myelin sheath. Conclusions: In preterm sheep, ACS exposure increased auditory nerve myelin area, potentially due to disruption of normal myelin deposition.

show abstract

“…Of those women who did not go into preterm labor (a total of 71%) 82% received a combination of tocolysis, corticosteroids and/or antibiotics. By administering corticosteroids unnecessarily, the subsequent effect of an additional round, if administered when truly needed, may be compromised [19] [20]. Administering tocolysis needlessly can have a negative impact on maternal, fetal, and neonatal outcome [6] [21].…”

Section: Discussionmentioning

confidence: 99%

Comparison of PAMG-1 and phIGFBP-1 Tests for the Prediction of Preterm Delivery in Patients with Preterm Labor

Hadzi-Lega¹,

Maier²,

Helmer³

et al. 2017

OJOG

View full text Add to dashboard Cite

Objective: To compare PAMG-1 and phIGFBP-1 tests in predicting impending spontaneous preterm delivery within 7 days upon presentation in pregnant women with symptoms of preterm labor. Study Design: From September 2014 to April 2015 women with singleton gestation, symptoms of preterm labor, GA 22 -35, participated in this prospective cohort study upon admission. Recruited patients had intact membranes and a minimal cervical dilatation of ≤3 cm. Vaginal swabs for phIGFBP-1 and PAMG-1 were taken in addition to routine treatment. Biochemical test results were blinded and had no effect on management of patients. Results: A total of 96 patients were screened for inclusion into the trial; 57 met the inclusion criteria for final analysis. The PAMG-1 test was positive in 5.7% of patients, while phIGFBP-1 test was positive in 29.8% of patients. The prediction of spontaneous preterm delivery within 7 days of admission in patients with a cervical length < 25 mm (30%), the PAMG-1 test and phIGFBP-1 test showed a SN of 100% and 100%; SP of 83.3% and 50.0%, (p ≤ 0.05); PPV of 71.4% and 45.5%; and NPV of 100% and 100%. 89.5% of women who received corticosteroids and 84.2% of women who received tocolysis did not go into preterm labor within one week. Conclusion: Our study supports the high negative predictability of biochemical tests to rule out spontaneous preterm labor in patients with a short cervix. However, our study strongly suggests that the PAMG-1 test is more accurate for predicting imminent spontaneous preterm delivery as compared to phIGFBP-1. These findings can significantly reduce economic burden caused by unnecessary admission and treatment of patients suspected of preterm labor. Such a reduction in the use of corticosteroids and tocolytics would lead to a reduction in the short and long term health effects associated with the use of

show abstract

Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial

Cited by 330 publications

References 21 publications

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep

Comparison of PAMG-1 and phIGFBP-1 Tests for the Prediction of Preterm Delivery in Patients with Preterm Labor

Contact Info

Product

Resources

About