The current study showed that antenatal MgSO4 was associated with low incidence of intestinal morbidities requiring surgery in preterm infants with GA less than 26 weeks. In the total study population, duration of exposure to antenatal MgSO4 was associated with decreased risk of intestinal injury needing surgery. There were no differences in mortality and other morbidities such as RDS, IVH and BPD between infants with and without antenatal MgSO4.
Antenatal MgSO4 has been used widely according to maternal and fetal conditions. Since benefits in terms of the neurodevelopmental outcomes were found in prospective randomized trials [2, 3], antenatal MgSO4 is now recommended for fetal neuroprotection in anticipation of preterm delivery in very preterm infants . As the use of antenatal MgSO4 has been highlighted, concerns have been raised regarding the neonatal adverse effects of antenatal MgSO4 because magnesium can block calcium entry into cells, leading to muscle weakness and intestinal atony in the offspring.
A clinical study showed a significant negative relationship between the mean blood flow velocity and the time from birth to the blood flow velocity measurement in antenatal MgSO4-exposed infants. In the secondary analysis of a prospective study, antenatal exposure to MgSO4 was associated with death or severe NEC in infants with a GA less than 26 weeks.[2, 10] Furthermore, a study of historical comparisons by Rattray et al reported that antenatal MgSO4 was associated with SIP and death.
However, another secondary analysis of a prospective trial reported that newborns with higher magnesium levels did not show any adverse non-neurological effects. Moreover, a meta-analysis of 5 randomized controlled studies concluded that there were no statistically significant differences in neonatal secondary outcomes, such as IVH, periventricular leukomalacia, NEC, RDS, ROP or chronic lung disease.
In the aforementioned secondary analysis study, although the combined outcome of death and severe NEC was associated with maternal antenatal MgSO4 administration in infants who were GA less than 26 weeks, NEC alone was not associated with antenatal MgSO4. Caution should be taken in the interpretation of the combined outcome of NEC and death because the two conditions were not competitive as death and BPD. Although Rattray et al reported the association between antenatal MgSO4 and SIP, but SGA was not included in the analysis. As the development of intestinal morbidities may be influenced by various causes, factors such as GA, SGA and medication history should be considered and coanalyzed to investigate factors associated with these conditions. For instance, SIP was associated with intrauterine growth restriction and PDA with delayed meconium passage in VLBW infants.[21, 22]
Although this was a retrospective study, the cumulative dose of antenatal MgSO4, duration of antenatal MgSO4 and level of magnesium were calculated and analyzed thoroughly. Factors associated with intestinal morbidities such as GA, SGA, and treated PDA were also reviewed. The results of the present study are consistent with the report from a nationwide database from North America, reporting that antenatal MgSO4 exposure in extremely preterm neonates was associated with reduced risk of a combined outcome of death, NEC and SIP. In a retrospective study from a tertiary-level NICU, cumulative dose of MgSO4 was associated with a combined outcome of death, NEC and SIP. Although a protective role of antenatal MgSO4 has been raised, the physiologically beneficial effect of magnesium on the intestine of preterm infants is not yet fully understood. One study of grass carp showed that magnesium deficiency suppressed the growth and damaged the intestinal structural integrity of the fish. A preclinical study of mice demonstrated that prophylactic oral administration of magnesium ameliorates induced colitis through the inhibition of colonic mast cell activation.
This was a single-center retrospective design, and the indications for antenatal MgSO4 included not only neuroprotection but also preterm labor. However, the dosages of the antenatal MgSO4 treatments for preterm labor and for neuroprotection were similar in our institution, and the data regarding duration, cumulative dosage and level of serum magnesium were reviewed. Mothers with preeclampsia, an important indication for antenatal MgSO4, were excluded because the maternal environment in this condition can affect vascular development of the intestine.[27, 28]