Is tocolytic magnesium sulphate associated with increased total paediatric mortality?

Mittendorf, Robert; Covert, Robert F.; Boinan, Julie; Khoshnood, Babak; Lee, Kwang-Sun; Siegler, Mark

doi:10.1016/s0140-6736(97)24047-x

Cited by 220 publications

(108 citation statements)

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“…Is it possible, for example, that some yet to be understood relationship between LSV and IVH, and the consequences of the latter, will ultimately provide an explanation for some of the unexpected mortalities in MagNET? 13 The question is asked in view of our previous report of an association between serious neurologic injury (Grade III IVH) and pediatric deaths observed in our study 27 as well as our previous report of a significant association between levels of maternal serum ionized magnesium circulating at the time of delivery and the subsequent outcome of neonatal intraventicular hemorrhage. 16 The anticoagulant properties of magnesium have now been reported by several investigators.…”

Section: Discussionmentioning

confidence: 89%

“…The original report of the unexpected total pediatric mortality associated with tocolytic doses of magnesium sulfate, appeared as a cautionary Research Letter in The Lancet. 13 It was accompanied by a Commentary solicited by the editors from two prominent London physicians. 14 A detailed methodology and the official report of the adverse outcomes that occurred in MagNET can be found in the American Journal of Obstetrics and Gynecology, 15 thus, they will appear here only in abbreviated form.…”

Section: Methodsmentioning

confidence: 99%

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Association between Lenticulostriate Vasculopathy (LSV) and Neonatal Intraventricular Hemorrhage (IVH)

et al. 2004

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OBJECTIVES:To determine whether there is an unconfounded association between neonatal intraventricular hemorrhage (IVH) and lenticulostriate vasculopathy (LSV (also known as thalamostriate or mineralizing vasculopathy)). STUDY DESIGN:During the conduct of the Magnesium and Neurologic Endpoints Trial (MagNET), a randomized controlled trial involving maternal, hence fetal, exposure to antenatal magnesium sulfate in the context of preterm labor, head ultrasounds were obtained for each of the surviving neonates. Because of our previous experience in the diagnosis of LSV, when ascertaining the presence of IVH, as called for by the research protocol of our study, the presence or absence of LSV was also determined. RESULTS:We found LSV to be relatively prevalent (10% (14 of 140) among surviving babies). More importantly, it was significantly associated with the occurrence of neonatal IVH, even when controlled for possible confounding (adjusted OR 9.8, 95% confidence interval 1.3 to 73.1; p ¼ 0.03). CONCLUSION:Given the known relationships between IVH and neonatal morbidity and mortality, the finding of a statistically significant association between neonatal IVH and LSV may suggest more substantial implications for the latter than previously believed.

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Section: Discussionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Association between Lenticulostriate Vasculopathy (LSV) and Neonatal Intraventricular Hemorrhage (IVH)

et al. 2004

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“…Magnesium sulfate tocolysis has been associated with various neonatal morbidities and mortality. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] The specific association of PIE with increased mortality in ELBW infants was not previously documented. Preterm labor is associated with elevated concentrations of fetal proinflammatory cytokines and other mediators.…”

Section: Discussionmentioning

confidence: 99%

Risk factors and clinical outcomes of pulmonary interstitial emphysema in extremely low birth weight infants

2006

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Objective: We studied the ante-and postnatal risk factors and clinical outcomes associated with pulmonary interstitial emphysema (PIE) in extremely low birth weight infants (ELBW, <1000 g at birth) in the present era of tocolytics, antenatal steroid and postnatal surfactant administration. Study design:This was a retrospective case-controlled study of all ELBW admitted consecutively during a designated study-period in a level III nursery. Data were analyzed by performing univariate and multivariate analysis as applicable.Results: Infants with PIE had lower 1 and 5 min Apgar scores (P ¼ 0.04 and 0.003 respectively), increased surfactant utilization (P ¼ 0.004), higher maximum inspired oxygen concentration (P ¼ 0.04) and mean airway pressure administration (P ¼ 0.02) during the first week of life, and increased neonatal mortality (P ¼ 0.01). They received higher antenatal doses of magnesium sulfate (MgSO 4 ) (P ¼ 0.02). 56% of infants with PIE were exposed to more than 10 g of MgSO 4 (Mg10), compared to 15% in non-PIE group (P ¼ 0.01). The multivariate logistic regression analysis including significant co-variates revealed an independent association between Mg10 and PIE (P ¼ 0.01, Odds ratio 19.8, 95% CI 1.5-263).Conclusion: Pulmonary interstitial emphysema is associated with increased mortality in ELBW infants. Mg10 is an independent risk factor for PIE in this population.

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“…5,6,17 A random-effects model meta-analysis combining data from this study with one by Cox et al 18 showed a statistically significant association between tocolytic magnesium and total pediatric death (AR ¼ 10.7, 95% CI ¼ 3.9 to 17.6). 2 In addition to these studies, others have demonstrated an association of magnesium exposure with adverse infant outcome. 1,4,[19][20][21] Most convincing was a Cochrane review by Crowther et al 22 of 23 trails assessing the safety and efficacy of magnesium tocolysis.…”

Section: Discussionmentioning

confidence: 97%

“…However, the use of tocolytics in the management of PTL has not been proven to prevent neonatal morbidity and mortality, and may have potential harmful effects on infants. [1][2][3][4] This lack of consensus about the efficacy and safety of tocolysis must be evaluated within the broader context that survival of infants delivered at tertiary care centers has improved annually, particularly for the subset of very premature infants (25 to 32 weeks gestational age). [5][6][7][8] The purpose of this study is two-fold: firstly, to examine whether maternal exposure to tocolytics is associated with subsequent increases in duration of infant hospitalization, transfer to another facility, cost as a result of neonatal complications, and infant rehospitalization within the first year of life compared to infants whose mothers had PTL and were not treated with tocolysis; and secondly, to examine morbidity and mortality among infants of mothers with PTL who did and did not receive tocolysis.…”

Section: Introductionmentioning

confidence: 99%

Hospitalization and Infant Outcomes among Women Exposed and Unexposed to Tocolysis

2004

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OBJECTIVE:To examine whether infants exposed to tocolytics are at increased risk for selected adverse clinical and hospitalization outcomes. STUDY DESIGN:We conducted a population-based cohort study of women with preterm labor, in Washington State from 1989 to 2001 (N ¼ 79,679), using linked hospitalization records. Relative risks for infant outcomes were estimated using multivariate logistic regression. RESULTS:Adjusted risk estimates for infants exposed to tocolysis were greater for respiratory distress (RR ¼ 1.5, 95% CI 1.4 to 1.6), intubation (RR ¼ 1.4, 95% CI 1.2 to 1.5), and bacterial infection (RR ¼ 1.6, 95% CI 1.4 to 1.8). Exposed infants were also more likely to have birth hospitalizations >2 days (RR ¼ 1.4, 95% CI 1.3 to 1.4), require transfer (RR ¼ 1.5, 95% CI 1.3 to 1.8), have increased hospital costs (RR ¼ 2.3, 95% CI 2.2 to 2.4), and require readmisssion within the first year of life (RR ¼ 1.2, 95% CI 1.1 to 1.3). CONCLUSION:Infants exposed to tocolytics appeared to have relatively poorer hospitalization and clinical outcomes; significant benefits were not observed.

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Is tocolytic magnesium sulphate associated with increased total paediatric mortality?

Cited by 220 publications

References 4 publications

Association between Lenticulostriate Vasculopathy (LSV) and Neonatal Intraventricular Hemorrhage (IVH)

Association between Lenticulostriate Vasculopathy (LSV) and Neonatal Intraventricular Hemorrhage (IVH)

Risk factors and clinical outcomes of pulmonary interstitial emphysema in extremely low birth weight infants

Hospitalization and Infant Outcomes among Women Exposed and Unexposed to Tocolysis

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