Research
ajog.org
OBSTETRICS
Antenatal magnesium sulfate exposure and acute cardiorespiratory events in preterm infants Lilia C. De Jesus, MD; Beena G. Sood, MD, MS; Seetha Shankaran, MD; Douglas Kendrick, MStat; Abhik Das, PhD; Edward F. Bell, MD; Barbara J. Stoll, MD; Abbot R. Laptook, MD; Michele C. Walsh, MD, MS; Waldemar A. Carlo, MD; Pablo J. Sanchez, MD; Krisa P. Van Meurs, MD; Rebecca Bara, RN; Ellen C. Hale, RN, BS; Nancy S. Newman, RN; M. Bethany Ball, BS, CCRC; Rosemary D. Higgins, MD; for the Eunice Kennedy Shriver National Institute of Health and Human Development Neonatal Research Network OBJECTIVE: Antenatal magnesium (anteMg) is used for various obstetric
indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg. STUDY DESIGN: This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network’s Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates. RESULTS: We evaluated 1544 infants 72 h of age; d Defined by Bell staging; e Presence of intraventricular or intraparenchymal hemorrhage on head ultrasound; f Based on cranial ultrasound findings at 28 d or 36 wk postmenstrual age; g Respiratory support includes conventional ventilation, highfrequency ventilation, nasal synchronized intermittent mandatory ventilation, continuous positive airway pressure; h Cumulative days on respiratory support or oxygen support were analyzed solely on survivorsedeaths were excluded; i Analyzed with Kaplan-Meier log rank test; j P value < .05 is considered significant.
De Jesus. Antenatal magnesium and acute events in preterm infants. Am J Obstet Gynecol 2015.
duration of MV. Again, this change in practice over the last decade strongly influenced the results of the study with fewer infants in the anteMg group on invasive MV by day 3 of life.22,23 Although previous studies found no association between anteMg exposure and risk for hypotension in infants,13,18 our study showed that infants exposed to anteMg received more fluid boluses but less frequent corticosteroids treatment for hypotension. While magnesium exposure can help stabilize blood pressure in the first 48 hours of life24
and improve cardiovascular function by regulation of vascular tone,3 volume expansion has been shown to improve the superior vena cava flow among preterm infants.25 Similarly, the secondary study from the Australian Collaborative Trial of MgSO4 investigating the neonatal cardiovascular effects of anteMg showed low superior vena cava flow on cardiac echocardiography at 10-12 hours of age and higher use of volume expansion among infants exposed to anteMg compared to those not exposed.26
94.e5 American Journal of Obstetrics & Gynecology JANUARY 2015
Low systemic blood flow that may contribute to hypotension in preterm infants during the first day of life is associated with decreasing gestational age, increasing mean airway pressure, and reduction in myocardial contractility.27,28 While there were more infants in the anteMg group that had ANS exposure, they were also less likely to be on invasive MV by day 3 of life and thus, had lower mean airway pressure. Since ANS exposure among preterm infants has been associated with higher mean systemic blood pressure and reduced need for blood pressure support during the first 24-48 hours after birth,29,30 this may explain our finding of lower risk for hypotension treatment among infants in the anteMg group. Overall, infants who were exposed to anteMg received less treatment for hypotension despite younger gestational age maybe because they also had more ANS exposure and less invasive MV. Our study has several limitations. First, indications for use, dosages, and receipt of anteMg in a previous admission were not collected in the GDB registry. The dosages for anteMg vary31 with each indication and the use of high dosages leading to high postnatal serum magnesium levels can certainly affect the CR status of the infant at birth.10 Despite this limitation, the study period chosen reflects current obstetrical practices, as most women presenting in preterm labor are now receiving MgSO4 for fetal neuroprotection. In addition, the dosage range used for neuroprotection has not been shown to result in high postnatal serum magnesium levels that would be associated with acute CR events at birth. Other limitations include the retrospective nature of the study, reliance on information in the database, and missing information in the database. Lastly, we do not have information regarding the serum magnesium levels of the mothers. The strengths of this study are the large number and diverse group of high-risk preterm infants included in the realworld setting outside a randomized clinical trial setting. In addition, the study period chosen is relatively recent and so reflects recent practice with regards to anteMg use.
Obstetrics
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TABLE 4
Multivariate logistic regression model estimating effects of antenatal magnesium exposure and risk of acute cardiorespiratory events CR events
P value
Odds ratio
95% CI
1.20
(0.88e1.65)
.246
1.22
(0.65e2.30)
.540
0.78
(0.58e1.06)
.109
0.65
(0.40e1.04)
.070
0.54
(0.41e0.72)
< .0001d
Hypotension
0.70
(0.51e0.97)
.031d
PDA (medical and surgical)
1.06
(0.80e1.40)
.696
DR intubation Day 1 respiratory support
a,b
c
Day 1 invasive MV
Day 3 respiratory support
a
c
Day 3 invasive MV
Covariates: center, gestational age, antenatal corticosteroids, pregnancy-induced hypertension/eclampsia. CI, confidence interval; CR, cardiorespiratory; DR, delivery room; MV, mechanical ventilation; PDA, patent ductus arteriosus. a
Includes conventional ventilation, high-frequency ventilation, nasal synchronized intermittent mandatory ventilation, continuous positive airway pressure; b Four centers that had 0 cells were combined with other centers so that modeling could produce valid results; c Includes conventional ventilation and high-frequency ventilation only; d P value < .05 is considered significant.
De Jesus. Antenatal magnesium and acute events in preterm infants. Am J Obstet Gynecol 2015.
In conclusion, the use of anteMg for common obstetric indications was not associated with an increase in acute CR events in preterm infants age
ajog.org
OBSTETRICS
Antenatal magnesium sulfate exposure and acute cardiorespiratory events in preterm infants Lilia C. De Jesus, MD; Beena G. Sood, MD, MS; Seetha Shankaran, MD; Douglas Kendrick, MStat; Abhik Das, PhD; Edward F. Bell, MD; Barbara J. Stoll, MD; Abbot R. Laptook, MD; Michele C. Walsh, MD, MS; Waldemar A. Carlo, MD; Pablo J. Sanchez, MD; Krisa P. Van Meurs, MD; Rebecca Bara, RN; Ellen C. Hale, RN, BS; Nancy S. Newman, RN; M. Bethany Ball, BS, CCRC; Rosemary D. Higgins, MD; for the Eunice Kennedy Shriver National Institute of Health and Human Development Neonatal Research Network OBJECTIVE: Antenatal magnesium (anteMg) is used for various obstetric
indications including fetal neuroprotection. Infants exposed to anteMg may be at risk for respiratory depression and delivery room (DR) resuscitation. The study objective was to compare the risk of acute cardiorespiratory events among preterm infants who were and were not exposed to anteMg. STUDY DESIGN: This was a retrospective analysis of prospective data collected in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network’s Generic Database from April 1, 2011, through March 31, 2012. The primary outcome was DR intubation or respiratory support at birth or on day 1 of life. Secondary outcomes were invasive mechanical ventilation, hypotension treatment, neonatal morbidities, and mortality. Logistic regression analysis evaluated the risk of primary outcome after adjustment for covariates. RESULTS: We evaluated 1544 infants 72 h of age; d Defined by Bell staging; e Presence of intraventricular or intraparenchymal hemorrhage on head ultrasound; f Based on cranial ultrasound findings at 28 d or 36 wk postmenstrual age; g Respiratory support includes conventional ventilation, highfrequency ventilation, nasal synchronized intermittent mandatory ventilation, continuous positive airway pressure; h Cumulative days on respiratory support or oxygen support were analyzed solely on survivorsedeaths were excluded; i Analyzed with Kaplan-Meier log rank test; j P value < .05 is considered significant.
De Jesus. Antenatal magnesium and acute events in preterm infants. Am J Obstet Gynecol 2015.
duration of MV. Again, this change in practice over the last decade strongly influenced the results of the study with fewer infants in the anteMg group on invasive MV by day 3 of life.22,23 Although previous studies found no association between anteMg exposure and risk for hypotension in infants,13,18 our study showed that infants exposed to anteMg received more fluid boluses but less frequent corticosteroids treatment for hypotension. While magnesium exposure can help stabilize blood pressure in the first 48 hours of life24
and improve cardiovascular function by regulation of vascular tone,3 volume expansion has been shown to improve the superior vena cava flow among preterm infants.25 Similarly, the secondary study from the Australian Collaborative Trial of MgSO4 investigating the neonatal cardiovascular effects of anteMg showed low superior vena cava flow on cardiac echocardiography at 10-12 hours of age and higher use of volume expansion among infants exposed to anteMg compared to those not exposed.26
94.e5 American Journal of Obstetrics & Gynecology JANUARY 2015
Low systemic blood flow that may contribute to hypotension in preterm infants during the first day of life is associated with decreasing gestational age, increasing mean airway pressure, and reduction in myocardial contractility.27,28 While there were more infants in the anteMg group that had ANS exposure, they were also less likely to be on invasive MV by day 3 of life and thus, had lower mean airway pressure. Since ANS exposure among preterm infants has been associated with higher mean systemic blood pressure and reduced need for blood pressure support during the first 24-48 hours after birth,29,30 this may explain our finding of lower risk for hypotension treatment among infants in the anteMg group. Overall, infants who were exposed to anteMg received less treatment for hypotension despite younger gestational age maybe because they also had more ANS exposure and less invasive MV. Our study has several limitations. First, indications for use, dosages, and receipt of anteMg in a previous admission were not collected in the GDB registry. The dosages for anteMg vary31 with each indication and the use of high dosages leading to high postnatal serum magnesium levels can certainly affect the CR status of the infant at birth.10 Despite this limitation, the study period chosen reflects current obstetrical practices, as most women presenting in preterm labor are now receiving MgSO4 for fetal neuroprotection. In addition, the dosage range used for neuroprotection has not been shown to result in high postnatal serum magnesium levels that would be associated with acute CR events at birth. Other limitations include the retrospective nature of the study, reliance on information in the database, and missing information in the database. Lastly, we do not have information regarding the serum magnesium levels of the mothers. The strengths of this study are the large number and diverse group of high-risk preterm infants included in the realworld setting outside a randomized clinical trial setting. In addition, the study period chosen is relatively recent and so reflects recent practice with regards to anteMg use.
Obstetrics
ajog.org
TABLE 4
Multivariate logistic regression model estimating effects of antenatal magnesium exposure and risk of acute cardiorespiratory events CR events
P value
Odds ratio
95% CI
1.20
(0.88e1.65)
.246
1.22
(0.65e2.30)
.540
0.78
(0.58e1.06)
.109
0.65
(0.40e1.04)
.070
0.54
(0.41e0.72)
< .0001d
Hypotension
0.70
(0.51e0.97)
.031d
PDA (medical and surgical)
1.06
(0.80e1.40)
.696
DR intubation Day 1 respiratory support
a,b
c
Day 1 invasive MV
Day 3 respiratory support
a
c
Day 3 invasive MV
Covariates: center, gestational age, antenatal corticosteroids, pregnancy-induced hypertension/eclampsia. CI, confidence interval; CR, cardiorespiratory; DR, delivery room; MV, mechanical ventilation; PDA, patent ductus arteriosus. a
Includes conventional ventilation, high-frequency ventilation, nasal synchronized intermittent mandatory ventilation, continuous positive airway pressure; b Four centers that had 0 cells were combined with other centers so that modeling could produce valid results; c Includes conventional ventilation and high-frequency ventilation only; d P value < .05 is considered significant.
De Jesus. Antenatal magnesium and acute events in preterm infants. Am J Obstet Gynecol 2015.
In conclusion, the use of anteMg for common obstetric indications was not associated with an increase in acute CR events in preterm infants age
