Rahil Prasad

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Pediatrics LP 2

Intestinal Effects of Antenatal Magnesium Sulfate Exposure on Preterm Neonates

Date Completed: 21/6/2023

Clinical Attachment: NICU, Labasa Hospital

Activity from which the learning issue arose:

- While the activities at NICU are less hands on than other wards in the hospital it allows

us to learn more about the supportive management of patients admitted to NICU

- The NICU has the sickest neonates, mostly preterm, that require close monitoring and

optimization of physiological functions. One of the common problems encountered in the

NICU are delayed passage of meconium

- This led to my thinking that many babies in the NICU are born due to pregnancy

complications leading to prematurity and would be exposed to Magnesium for

Neuroprotection through interventions of the O&G team

- It would be interesting to see the effects the Magnesium has on neonatal intestinal

function

Learning Issue Identified:

- Prenatal Magnesium Exposure and its intestinal effects

Question

- Effect of Antenatal Magnesium Sulfate on Meconium Passage in Preterm Neonates

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Resources Used:

1. Sung, S.I. et al. (2022) ‘Increased risk of meconium-related ileus in extremely premature

infants exposed to antenatal magnesium sulfate’, Neonatology, 119(1), pp. 68–76.

doi:10.1159/000520452.

2. Kim, S.H. et al. (2021) ‘Antenatal magnesium sulfate and intestinal morbidities in

preterm infants with extremely low gestational age’, Pediatrics & Neonatology,

62(2), pp. 202–207. doi:10.1016/j.pedneo.2020.12.009.

3. Revenga et al. (2022) ‘Antenatal magnesium sulfate and delayed passage of meconium:

A multicentre study’, Anales de Pediatría, (97), pp. 383–389.

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Critically Assess These Resources

1. Sung and others published a cohort study in 2022 based in South Korea where they

compared the outcomes of babies exposed to prenatal Magnesium Sulfate to those

who were not. The authors addressed a clear question where they studied the association

of magnesium sulfate used for fetal neuroprotection to meconium related ileus in

extremely premature infants. The cohort selected were infants born between 22 weeks

and 26 weeks in a specific south korean hospital between 2012 and 2018. The cohort

represented the population that the authors were studying and only infants whose mothers

received magnesium, at 4g over 20 minutes and then 1g per hour for 24 hours were

chosen. The authors used the available medical records and everyone that should've been

included was included. The authors clearly defined meconium related ileus and selected

infants that met the criteria. The team used subjective measurements such as

anthropometry and enema studies and all subjects were classified into exposure groups

using the same procedures. All the outcomes were measured in the same way, and the

methods were the same when comparing results across the groups. All subjects enrolled

in the study were followed up till either their ileus resolved, they were discharged or died.

The authors found that Magnesium does increase the risk of meconium ileus with an OR

of 3.6 and CI of 95%.

2. Kim and others published a retrospective cohort study to find the effects of

magnesium sulfate on the intestinal morbidities that will require surgery in preterm

infants. The study was designed to find the effects of antenatal MgSO4 on neonatal

outcomes of preterm infants, especially requiring surgical intervention. The cohort was
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recruited from Seoul University who were born before 28 weeks of gestation from 2011

to 2015. The cohort was chosen to be representative. Measurements about the

complications of prematurity and intestinal morbidity were taken with objective

measurements of the number of treatments needed. The authors identified they did not

consider the effects of Magnesium on Colitis. Subjects were followed up with

information in their records and all were included in the study. The authors found some

benefit of MgSO4 in reduction of intestinal morbidity requiring surgical intervention.

Confidence intervals and P values were given by the authors. The results reflect the

population studied and help prove a beneficial response.

3. A cohort study was conducted by Revenga and others to find the association

between magnesium sulfate and delayed passage of meconium. The population

consisted of infants delivered before 32 weeks and failure to pass meconium within 48

hours of birth. Exposure was measured with a maternal dose of magnesium considered.

The outcomes were objectively measured with the time to bowel movement. Authors

identified maternal factors that may contribute to delayed meconium passing in neonates.

The infants were followed up throughout the study. The results showed that maternal

magnesium did not contribute to delayed meconium passing. The results were not

presented with confidence intervals and P values. The results reflected the population.
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Meconium Related Intestinal Morbidities in Preterm Infants Exposed to Antenatal

Magnesium Sulfate

The NICU in Labasa serves for the sickest neonates and preterm neonates. An important point to

consider when treating these infants is their antenatal history as maternal factors often lead to

premature deliveries. During my rotation in the Labasa NICU I encountered six different

premature infants and it was interesting how meticulously the nursing staff looked after their

input and output. I have also experienced maternal magnesium sulfate being used when a mother

is about to deliver preterm. As such I would like to explore the effect of Maternal Magnesium

Sulfate on meconium passage in premature neonates.

Neonatology Journal published a paper by Sung et al in 2022 where the authors explored the risk

of ileus in extremely premature infants whose mothers received magnesium sulfate. The authors

noted their anecdotal data of ileus in premature infants who have a history of magnesium sulfate.

The authors looked back at the medical records of 231 extremely premature infants (22 weeks to

26 weeks) over a period of 7 and classified them into 3 groups; before MgSO4 protocol was

adopted, during the protocol and after the protocol was dropped (Sung et al, 2022). The infant

characteristics were similar and all infants were otherwise given the same care. The results

showed that incidences of meconium related ileus that require surgical intervention was highest

during the time MgSO4 was used in all preterm deliveries. Furthermore, the Odd ratio was found

to be at 3.8 when exposure was compared to the diagnosis of meconium related ileus with a

confidence interval of 95%. As such the authors concluded that antenatal MgSO4 had increased

the incidence of meconium related ileus in premature infants less than 26 weeks. This is an
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interesting finding as MgSO4 is commonly used antenatally, and it increases curiosity into

whether increasing plasma Mg ions would increase the rates of meconium related ileus.

Kim and others published in Pediatrics and Neonatology their findings from a 2020 cohort study

that compared antenatal magnesium sulfate use to the incidences of intestinal disease in preterm

infants less than 28 weeks. The authors enrolled 181 preterm infants and categorized them into 2

groups; exposed to MgSO4 antenatally (maternal) and not exposed. The authors reported that the

exposed group had lower incidences of surgical intervention related to the intestines with an OR

of 0.393 (Kim et al, 2020)However, the length of exposure was not related to the incidence of

intestinal morbidities with an OR of 0.77. This study shows that MgSO4 generally reduces

intestinal morbidity in preterm infants, but shows an OR of 0.7 when comparing meconium

obstruction that may require surgery (4 in the no MgSO4 and 5 in the MgSO4). Therefore, the

authors concluded that MgSO4 given antenatally to the mother may have some protective effect

when considering intestinal morbidity. This result is interesting as it does not confirm the ideas

presented earlier but still shows some association.

A more recent study from Spain saw Revenga and others find possible association between

antenatal magnesium sulfate and delayed meconium passage. The authors analyzed the serum

magnesium levels to see if the concentration also had some association. There were 283 patients

enrolled from 2 centers where 53% experienced delayed meconium but this number was not

reflected in mothers that received magnesium. Interestingly, the authors noted that older

gestation was seen as a protective factor (OR of 0.8) but infants that received active resuscitation

had higher incidence of meconium passage delay. Moreover, the serum measurements of
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magnesium showed levels remained steady over 48 hours and there was no difference in the

incidence of meconium delay with increasing or decreasing serum levels. Therefore, this study

shows that the serum levels of magnesium do not influence the delay of meconium passage and

there is little association between exposure and outcome.

To conclude, the 3 studies discussed above present ideas that are somewhat similar. The

overarching themes suggest some link between delay of meconium passage but the association is

not well established. As such, I believe the role of magnesium administered antenatally must be

investigated in preterm infants with meconium related ileus or obstruction. Moreover, locally

these findings can make us more cautious when dealing with infants with obstruction and

increase our differential diagnosis scope.

(No. of words- 707)

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References

Sung, S.I. et al. (2022) ‘Increased risk of meconium-related ileus in extremely premature infants

exposed to antenatal magnesium sulfate’, Neonatology, 119(1), pp. 68–76.

doi:10.1159/000520452.

Kim, S.H. et al. (2021) ‘Antenatal magnesium sulfate and intestinal morbidities in preterm

infants with extremely low gestational age’, Pediatrics & Neonatology, 62(2), pp.

202–207. doi:10.1016/j.pedneo.2020.12.009.

Revenga et al. (2022) ‘Antenatal magnesium sulfate and delayed passage of meconium: A

multicentre study’, Anales de Pediatría, (97), pp. 383–389.

Critical Appraisal Skills Programme (2018). CASP (Cohort Study) Checklist. [online]

Available at: https://casp-uk.net/casp-tools-checklists/. Accessed: Date Accessed- 19/6/2023