Objective
The administration of antenatal corticosteroids in the late preterm period reduces neonatal morbidity but results in more frequent neonatal hypoglycemia. , We aimed to evaluate whether there is an association between time from steroid administration to delivery and neonatal hypoglycemia.
Study Design
This was a retrospective cohort of patients with singleton pregnancies admitted between 34 0/7 and 36 6/7 weeks of gestation who received at least 1 dose of antenatal corticosteroids. The primary exposure was time from first dose of steroid to delivery, which we categorically examined as <48 vs ≥48 hours. This threshold was chosen a priori based on previous research indicating that 48 hours was the desired time needed before delivery to achieve the maximum benefit of antenatal corticosteroids. The primary outcome was neonatal hypoglycemia, defined as any neonatal blood glucose value of ≤35 mg/dL in the first 24 hours of life. We chose this value based on consultation with the neonatologists at our institution, as representative of the value at which they felt hypoglycemia was clinically significant. The secondary outcomes included admission to the neonatal intensive care unit (NICU), neonatal intravenous dextrose administration, and respiratory morbidity.
We conducted sensitivity analyses with different blood glucose thresholds (40 mg/dL, 50 mg/dL, and 60 mg/dL) used to define hypoglycemia. Furthermore, we varied how we categorized time since administration, modeling latency using 4 categories: <8 hours, 8 to <24 hours, 24 to <48 hours, and ≥48 hours. We used chi-squared tests for univariable comparisons and logistic regression to adjust for confounders.
Results
Of 302 individuals, 49 (16.2%) had steroid latency of ≥48 hours ( Supplemental Figure 1 ). Sample summary statistics are in Supplemental Table 1 . There was no difference in the frequency of hypoglycemia by steroid latency (14.3% among those with a latency of ≥48 hours vs 19.0% of those with a latency of <48 hours; P =.44). This finding remained nonsignificant after accounting for confounders (adjusted odds ratio [aOR], 0.87; 95% confidence interval [CI], 0.36–2.12). Altering the hypoglycemia threshold did not change the results ( Table ) . NICU admission, dextrose administration, and respiratory morbidity were not associated with steroid latency ( Supplemental Figure 2 ).
| Neonatal hypoglycemia thresholds (mg/dL) | Betamethasone latency<48 h (n=253) | Betamethasone latency≥48 h (n=49) | P value a | Adjusted OR b | 95% CI |
|---|---|---|---|---|---|
| ≤35 | 48 (19.0) | 7 (14.3) | .44 | 0.87 | 0.36–2.12 |
| ≤40 | 85 (33.6) | 11 (22.4) | .13 | 0.65 | 0.31–1.38 |
| ≤50 | 172 (68.0) | 26 (53.1) | .04 | 0.62 | 0.32–1.19 |
| ≤60 | 173 (68.4) | 26 (53.1) | .04 | 0.61 | 0.32–1.17 |
a P value for chi-square tests
b ORs from logistic regression controlling for cesarean delivery, preeclampsia, and gestational age at delivery (wk).
When using 4 categories of time, we saw increased odds of hypoglycemia with a latency of 8 to <24 hours (aOR, 5.18; 95% CI, 1.89–14.7) and 24 to <48 hours (aOR, 7.62; 95% CI, 2.47–22.9) relative to <8 hours. By ≥48 hours after steroid administration, there was no statistically significant increase in the odds of hypoglycemia (aOR, 3.34; 95% CI, 0.92–11.5).
Conclusion
In this cohort, the risk of neonatal hypoglycemia initially increased; however, it returned to baseline at 48 hours after the administration of the first dose of corticosteroid in the late preterm period. The finding that the 8- to 48-hour window of time may represent a peak risk period for neonatal hypoglycemia was similar to that of other work: frequency of hypoglycemia peaks in the first 2 days after corticosteroid administration and then tapers off. This period corresponds to the peak of maternal hyperglycemia, which is aligned with the suspected mechanism of neonatal hypoglycemia resulting from elevated maternal blood glucose levels leading to increased fetal insulin production. Future work could focus on identifying patients who may derive the most benefit from antenatal late preterm corticosteroids.
Appendix
