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Effects of Different Doses of Antenatal Magnesium Sulfate Exposure on Short-Term Outcomes of Preterm Infants &lt; 32 weeks: A Retrospective Cohort Study

This retrospective cohort study of 451 preterm infants <32 weeks gestation found that antenatal magnesium sulfate exposure significantly reduces early mortality, particularly in infants <28 weeks, while also lowering the risk of hemodynamically significant patent ductus arteriosus in the 28–31⁺⁶ weeks subgroup but increasing the incidence of retinopathy of prematurity in the same group.

Original authors: Licong Lin, Xiaoling Hu, Zhihong Wang, Liping Xu, Wenwen Chen

Published 2026-09-28

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CC BY 4.0

Original authors: Licong Lin, Xiaoling Hu, Zhihong Wang, Liping Xu, Wenwen Chen

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

Every year, thousands of babies are born too soon, their tiny bodies still finishing the final stages of development that usually happen in the womb. For infants arriving before 32 weeks, the world is a harsh place; their organs are immature, and they face severe risks like bleeding in the brain or breathing difficulties that can be fatal within days. Doctors have long known that giving a specific mineral, magnesium sulfate, to mothers before these babies are born helps protect the baby's developing brain, significantly lowering the risk of cerebral palsy. This treatment is now a standard part of care for threatened preterm labor. However, because magnesium sulfate also relaxes blood vessels, some medical experts have worried that it might cause other problems, such as keeping a vital fetal blood vessel open when it should close, or causing other complications in the fragile newborn. The question remains: does the benefit of this brain protection come with hidden costs, and does the amount of medicine given change the outcome?

A team of researchers at Zhangzhou Municipal Hospital in Fujian Province set out to answer these questions by looking back at the medical records of 451 preterm infants born between June 2023 and December 2025. They focused on babies born before 32 weeks and sorted them into three groups based on how much magnesium sulfate their mothers received before delivery. One group received a standard, lower dose often used for brain protection, another group received a higher dose typically used for severe pregnancy complications like high blood pressure, and a third group received no magnesium sulfate at all. The researchers then tracked what happened to these babies during their first week of life and monitored them for common complications like bleeding in the brain, heart issues, and lung problems.

The study revealed a clear and reassuring picture regarding survival. Babies whose mothers received magnesium sulfate were far less likely to die within the first week of life compared to those who did not receive the treatment. This protective effect was not spread evenly across all ages; it was most powerful for the tiniest infants, those born before 28 weeks. In this extremely premature group, the death rate dropped from nearly one in four for untreated babies to just one in twenty for those whose mothers received the medication. For slightly older preterm babies between 28 and 31 weeks, the survival rates were already high, and the medication did not show a statistically significant difference in preventing early death, though it did not cause harm. The researchers confirmed that the medication itself was a strong factor in keeping these fragile infants alive, independent of other variables like birth weight or the type of delivery.

When the team looked at the specific complications that often plague preterm infants, the results offered further clarity on the safety of the treatment. Contrary to the fear that magnesium sulfate might keep the ductus arteriosus—a fetal blood vessel that should close after birth—open and cause heart strain, the study found the opposite in the 28-to-31-week group. Babies in this age range whose mothers received the medication were actually less likely to develop a significant, problematic opening in this vessel compared to those who did not. The treatment did not increase the risk of other serious issues like severe brain bleeds, lung disease, or intestinal damage. In fact, the data suggested that the medication was safe across the board, with no increase in the need for mechanical ventilation or other life-support measures.

One finding required a careful look, however. In the group of babies born between 28 and 31 weeks, those whose mothers received magnesium sulfate had a higher rate of retinopathy of prematurity, a condition affecting the eyes that can lead to vision problems. The researchers noted that this group of treated babies was also slightly smaller and born a bit earlier than the untreated group, factors that are known to increase the risk of eye issues. Because of these underlying differences, the study could not definitively say the medication caused the eye problems, but it flagged the association as something doctors should watch closely. In the tiniest group of babies under 28 weeks, no such increase in eye problems was seen, and the rates of other complications remained similar between treated and untreated infants.

Ultimately, this research paints a picture of magnesium sulfate as a vital tool that saves lives without introducing the feared side effects. The treatment appears to be most critical for the smallest, most vulnerable infants, offering them a significantly better chance of surviving their first week. While the study was limited by its single location and the relatively small number of patients in some categories, the results strongly support the continued use of this medication for brain protection. It suggests that the benefits of keeping these infants alive and stable far outweigh the risks, and that concerns about the medication causing heart or bowel issues may be unfounded. The findings reinforce the idea that for the most fragile newborns, this simple mineral treatment is a powerful shield against the dangers of being born too soon.

Technical Summary: Effects of Different Doses of Antenatal Magnesium Sulfate Exposure on Short-Term Outcomes of Preterm Infants < 32 Weeks

Problem Statement
Preterm infants born before 32 weeks of gestation face high risks of mortality and severe complications, including intracranial hemorrhage (IVH), white matter injury, and respiratory distress. While prenatal magnesium sulfate ( $MgSO_4$ ) is widely recommended for fetal neuroprotection (specifically to reduce cerebral palsy risk), its effects on other physiological systems remain controversial. As a calcium ion antagonist, $MgSO_4$ relaxes vascular smooth muscle, leading to concerns that it might delay ductus arteriosus closure (increasing hemodynamically significant patent ductus arteriosus, or hsPDA) or cause neonatal respiratory depression and intestinal injury. Furthermore, clinical dosing varies significantly depending on the indication (neuroprotection typically $\le$ 30g vs. treatment of preeclampsia or tocolysis often >30g), yet previous studies have largely analyzed $MgSO_4$ exposure as a monolithic variable without stratifying by dosage. This study addresses the gap in understanding how different cumulative doses of antenatal $MgSO_4$ affect short-term outcomes in preterm infants <32 weeks.

Methodology
This retrospective cohort study was conducted at the Affiliated Zhangzhou Hospital of Fujian Medical University between June 2023 and December 2025.

Subjects: 451 preterm infants (<32 weeks gestation) admitted to the NICU were enrolled. Infants with chromosomal abnormalities, congenital malformations, multiple pregnancies, or incomplete data were excluded.
Grouping: Participants were stratified into three groups based on the cumulative antenatal $MgSO_4$ $M g S O_{4}$ dose:
1. Low-dose group: $\le$ 30 g (n=143).
2. High-dose group: >30 g (n=21).
3. Non-exposure group: No maternal $MgSO_4$ administration (n=287).
Outcomes:
- Primary: Death within 1 week of birth, Grade III–IV IVH, and Periventricular Leukomalacia (PVL).
- Secondary: Bronchopulmonary dysplasia (BPD), hsPDA, necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, and duration of invasive mechanical ventilation.
Analysis: Multivariable logistic regression was used to identify independent risk factors for early death. Subgroup analyses were performed by gestational age (<28 weeks and 28–31 $^{+6}$ weeks) to compare outcomes between the combined exposure group (low + high dose) and the non-exposure group.

Key Results

Overall Mortality: Antenatal $MgSO_4$ exposure was identified as an independent protective factor against death within 1 week (OR=0.197, 95% CI: 0.051–0.759, P=0.018). The overall mortality rate was 5.8% (26/451), with the non-exposure group having the highest rate (8.0%) compared to the low-dose (2.1%) and high-dose (0%) groups.
Gestational Age Stratification (<28 weeks): In extremely preterm infants, $MgSO_4$ exposure significantly reduced 1-week mortality compared to non-exposure (5.1% vs. 24.0%, P=0.024). There was no significant difference in Grade III–IV IVH incidence between groups. No significant differences were observed in secondary complications (hsPDA, ROP, NEC, BPD) within this subgroup.
Gestational Age Stratification (28–31 $^{+6}$ weeks): In this subgroup, no significant difference was found in 1-week mortality (0.8% vs. 2.4%, P=0.509) or Grade III–IV IVH. However, the exposure group showed a significantly lower incidence of hsPDA at 2 weeks (3.9% vs. 12.0%, P=0.013). Conversely, the incidence of ROP was significantly higher in the exposure group (20.6% vs. 8.7%, P<0.001).
Complications: Across both subgroups, $MgSO_4$ exposure did not increase the risk of BPD, NEC, sepsis, or PVL. The duration of invasive mechanical ventilation was not significantly different between groups.

Key Contributions

Dose-Independent Protection: The study confirms that antenatal $MgSO_4$ exposure, regardless of whether the cumulative dose is $\le$ 30g or >30g, is associated with reduced early mortality in preterm infants <32 weeks.
Gestational Age Specificity: The protective effect against early mortality is primarily concentrated in extremely preterm infants (<28 weeks), with no statistically significant survival benefit observed in the 28–31 $^{+6}$ week subgroup.
Safety Profile regarding hsPDA: Contrary to the hypothesis that $MgSO_4$ delays ductus closure, the study found a reduced incidence of hsPDA at 2 weeks in the 28–31 $^{+6}$ week subgroup, suggesting the drug does not increase this risk in this population.
ROP Correlation: The study highlights a significant association between $MgSO_4$ exposure and higher ROP incidence in the 28–31 $^{+6}$ week subgroup, though the authors note this may be confounded by the fact that the exposed group in this subgroup had significantly lower gestational ages and birth weights than the non-exposed group.

Significance and Claims
The paper claims that antenatal magnesium sulfate exposure significantly reduces the risk of death within the first week of life for preterm infants <32 weeks, with the most substantial benefit observed in infants <28 weeks. The authors assert that this protective effect does not come at the cost of increased risks for major complications such as BPD, NEC, or severe IVH.

Regarding the increased ROP incidence in the 28–31 $^{+6}$ week subgroup, the authors exercise caution, suggesting it may be related to the inherent higher risk profile (lower gestational age and birth weight) of the exposed infants in that specific subgroup rather than a direct toxic effect of magnesium sulfate. They conclude that while $MgSO_4$ is safe and effective for early survival in extremely preterm infants, future multicenter, large-sample prospective studies are necessary to validate these findings, particularly regarding the potential impact on ROP and long-term neurodevelopmental outcomes. The study acknowledges limitations including its single-center retrospective design, small sample size in the high-dose and <28 week subgroups, and the inability to fully separate the effects of maternal disease (preeclampsia) from the drug effects in the high-dose group.

Technical Summary: Effects of Different Doses of Antenatal Magnesium Sulfate Exposure on Short-Term Outcomes of Preterm Infants < 32 Weeks

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