Effects of Maternal Diabetes on Respiratory Outcomes of Moderately Preterm Infants: Have We Made Progress?

Technical Summary: Effects of Maternal Diabetes on Respiratory Outcomes of Moderately Preterm Infants

Problem Statement
Infants of diabetic mothers (IDMs) have historically been identified as being at a significantly increased risk for neonatal respiratory distress syndrome (RDS). This risk is attributed to the inhibitory effects of maternal hyperglycemia and subsequent fetal hyperinsulinism on fetal surfactant synthesis and maturation. While the incidence of maternal diabetes (Type 1, Type 2, and Gestational) is rising globally, and medical management of diabetes during pregnancy has advanced significantly since the 1970s, it remains unclear whether these modern improvements in glycemic control have mitigated the respiratory morbidity associated with IDMs, particularly within the specific subset of moderately preterm infants (29 0/7 to 32 6/7 weeks gestation).

Methodology
This study is a retrospective, population-based observational analysis conducted at Rainbow Babies and Children's Hospital. The cohort consisted of 387 mother-infant dyads admitted to the Neonatal Intensive Care Unit (NICU) between 2019 and 2022.

• Inclusion Criteria: Gestational age (GA) between 29 0/7 and 32 6/7 weeks.
• Exclusion Criteria: Infants without available maternal information.
• Data Collection: Retrospective extraction from electronic medical records into a REDCap database.
• Variables: Maternal data included diabetes type (T1DM, T2DM, GDM), HbA1c, BMI, delivery mode, and antenatal steroid administration. Infant data included birth weight, RDS diagnosis, respiratory support duration, peak FiO2, and surfactant usage.
• Definitions: RDS was defined using the Vermont Oxford Network (VON) criteria, requiring supplemental oxygen to maintain PaO2 >50mmHg or SpO2 >85% within the first 24 hours, accompanied by a chest radiograph consistent with RDS.
• Statistical Analysis: Comparisons between IDMs and non-IDMs utilized chi-square/Fisher's exact tests for categorical variables and Student's t-test/Wilcoxon rank sum tests for continuous variables.

Key Results
Among the 387 infants, 15.8% (n=61) were IDMs. The mean gestational age for the cohort was 31.1 weeks.

• RDS Incidence: The overall incidence of RDS was 67.5%. Crucially, there was no statistically significant difference in the rate of RDS diagnosis between the IDM and non-IDM groups.
• Respiratory Support Needs: Despite similar RDS rates, IDMs demonstrated a significantly higher need for respiratory support.
  • Surfactant Use: IDMs had a higher rate of surfactant administration (47%) compared to non-IDMs (36%), though this trend did not reach statistical significance (p < 0.1).
  • Oxygen Requirements: IDMs required significantly higher peak FiO2 levels during the first 4–24 hours of life (p ≤ 0.03).
  • Weaning Time: The time required to wean IDMs to 21% FiO2 was significantly longer than for non-IDMs (p ≤ 0.03).
  • Duration of Support: There was a trend toward IDMs requiring more days on positive pressure respiratory support (5 days vs. 3 days for non-IDMs, p < 0.1).
• Maternal Factors: Mothers with pre-gestational diabetes had a significantly higher rate of cesarean sections (84.6% vs. 62.2%) and obesity compared to non-diabetic mothers.

Key Contributions
The study addresses a specific knowledge gap regarding respiratory outcomes in moderately preterm infants (29–32 weeks) exposed to maternal diabetes in the modern era of diabetes management. Unlike previous studies that may have included broader gestational age ranges or focused solely on the binary diagnosis of RDS, this research provides detailed respiratory metrics, including peak oxygen requirements and the duration of weaning. The authors highlight that while the diagnosis of RDS may not differ significantly between groups in this era, the severity and duration of respiratory support needs are measurably higher for IDMs.

Significance and Claims
The authors conclude that despite significant advancements in maternal diabetes management and glycemic control, IDMs continue to face increased respiratory morbidity in the immediate neonatal period. Specifically, the paper claims that while the incidence of RDS diagnosis may be comparable to non-IDMs in this gestational window, IDMs require prolonged supplemental oxygen and positive pressure support.

The significance of these findings lies in the potential downstream effects of this respiratory morbidity, which the authors note may include:

• Negative impacts on maternal-fetal bonding.
• Delays in oral feeding and breastfeeding initiation.
• Increased length of hospital stay.

The paper modestly suggests that further research is required to fully understand the complex mechanisms of maternal diabetes on respiratory outcomes in moderately preterm infants and to better standardize RDS as a clinical research outcome. The authors acknowledge limitations, including the retrospective nature of the study and the lack of data on specific maternal glycemic control metrics during labor, as well as potential clinical bias where providers might be more aggressive in initiating respiratory support for IDMs based on perceived risk.