Center for Women's Reproductive Health, The University of Alabama at Birmingham, Birmingham, AL (Drs Battarbee, Ye, Szychowski, Casey, and Tita); Departments of Obstetrics and Gynecology (Drs Battarbee, Ye, Szychowski, Casey, and Tita) and Biostatistics (Dr Szychowski), The University of Alabama at Birmingham, Birmingham, AL.
Center for Women's Reproductive Health, The University of Alabama at Birmingham, Birmingham, AL (Drs Battarbee, Ye, Szychowski, Casey, and Tita); Departments of Obstetrics and Gynecology (Drs Battarbee, Ye, Szychowski, Casey, and Tita) and Biostatistics (Dr Szychowski), The University of Alabama at Birmingham, Birmingham, AL.
Am J Obstet Gynecol MFM. 2022 Jul;4(4):100625. doi: 10.1016/j.ajogmf.2022.100625. Epub 2022 Mar 26.
Late preterm steroid administration can induce transient maternal and thus fetal hyperglycemia, which can increase production of fetal insulin and C-peptide. Infants delivered in this setting are subsequently at increased risk for hypoglycemia. Although maternal glycemic control before delivery is a key component of care for parturients with diabetes, this intervention has not been studied in the setting of late preterm steroid administration.
This study aimed to determine the effect of maternal screening for and treatment of hyperglycemia after late preterm steroid administration on fetal C-peptide levels and other metabolic markers.
This was a multicenter, randomized trial (NCT03076775) of nondiabetic parturients with a singleton gestation receiving betamethasone at 34 0/7 weeks to 36 5/7 weeks for anticipated preterm birth. Participants randomized to maternal glycemic control received fasting and 1-hour postprandial or serial intrapartum capillary blood glucose screening with insulin treatment as indicated. Those randomized to expectant management did not receive any glucose screening or treatment. The primary outcome was fetal C-peptide level measured from umbilical cord blood at delivery. Secondary outcomes included other fetal metabolic markers and neonatal hypoglycemia (glucose level <40 mg/dL). Baseline characteristics and outcomes were compared between the groups. We estimated that we would need a sample size of 144 to provide >90% power to show a 1 ng/mL decrease in C-peptide concentration (±1.5 ng/mL) at ⍺=0.05 using a 2-sample t test and 1 interim analysis. After the interim analysis, the trial was stopped for futility.
Of 491 screened parturients, 163 (33%) were deemed eligible and 86 (53%) were randomized to 1 of the treatment groups (June 2017 to February 2021). One person was lost to follow-up because of delivery at another hospital. Baseline characteristics were similar between groups. The median interval from betamethasone administration to delivery was 24 hours (interquartile range, 13-96 hours) and did not differ between groups (P=.82). Most (82%) randomized to maternal glycemic control had hyperglycemia: 80% had at least 1 fasting glucose level >95 mg/dL, 75% had at least one 1-hour postprandial glucose level >140 mg/dL, and 80% had at least 1 intrapartum glucose level >110 mg/dL. In addition, 15% had at least 1 glucose level >180 mg/dL. None had maternal hypoglycemia after insulin treatment. Compared with expectant management, maternal glycemic control did not affect the median fetal C-peptide level (1.02; interquartile range, 0.52-1.85 vs 1.09; interquartile range, 0.61-1.65; P=.97) or other metabolic markers. Maternal glycemic control also did not affect neonatal hypoglycemia (49% vs 51%; P=.83) or other secondary neonatal or maternal outcomes. There was no evidence of effect modification by gestational age or body mass index at randomization, indication for betamethasone, duration from betamethasone to delivery, maternal race or ethnicity, or neonatal sex. In addition, the results were unchanged in a sensitivity analysis using a per-protocol approach.
Maternal hyperglycemia was observed in most nondiabetic parturients after receiving late preterm betamethasone. However, there was no improvement in fetal metabolic status, neonatal hypoglycemia, or other neonatal or maternal outcomes with maternal glycemic control. Therefore, maternal glucose surveillance and treatment does not seem to be beneficial in nondiabetic parturients receiving late preterm steroids.
晚期早产儿给予类固醇后会导致短暂的母源性及胎儿高血糖，从而增加胎儿胰岛素和 C 肽的产生。在此背景下分娩的婴儿随后发生低血糖的风险增加。尽管在糖尿病产妇的分娩护理中，控制母体血糖是一个关键组成部分，但在晚期早产儿给予类固醇的情况下，尚未对此干预措施进行研究。
本研究旨在确定晚期早产儿给予类固醇后，母体血糖筛查和治疗对胎儿 C 肽水平和其他代谢标志物的影响。
这是一项多中心、随机试验（NCT03076775），纳入了接受倍他米松治疗的单胎妊娠孕妇，妊娠时间为 34 0/7 周到 36 5/7 周，预计早产。随机分配至母体血糖控制组的患者接受禁食和 1 小时餐后或连续产时毛细血管血糖筛查，并根据需要给予胰岛素治疗。随机分配至期待管理组的患者未接受任何血糖筛查或治疗。主要结局是分娩时脐静脉血中胎儿 C 肽水平。次要结局包括其他胎儿代谢标志物和新生儿低血糖（血糖水平<40mg/dL）。比较两组间的基线特征和结局。我们估计需要 144 例样本量，才能在 α=0.05 时使用两样本 t 检验和 1 次中期分析，提供>90%的效能来显示 C 肽浓度降低 1ng/mL（±1.5ng/mL）。中期分析后，由于在其他医院分娩，试验停止。
在筛选的 491 例产妇中，有 163 例（33%）符合条件，86 例（53%）被随机分配至 1 个治疗组（2017 年 6 月至 2021 年 2 月）。由于在其他医院分娩，1 人失访。两组间的基线特征相似。从倍他米松给药到分娩的中位时间间隔为 24 小时（四分位距，13-96 小时），两组间无差异（P=0.82）。大多数（82%）随机分配至母体血糖控制组的患者存在高血糖：80%有至少 1 次空腹血糖水平>95mg/dL，75%有至少 1 次 1 小时餐后血糖水平>140mg/dL，80%有至少 1 次产时血糖水平>110mg/dL。此外，15%有至少 1 次血糖水平>180mg/dL。在接受胰岛素治疗后，没有产妇发生低血糖。与期待管理相比，母体血糖控制并未影响胎儿 C 肽水平的中位数（1.02；四分位距，0.52-1.85 与 1.09；四分位距，0.61-1.65；P=0.97）或其他代谢标志物。母体血糖控制也不影响新生儿低血糖（49%与 51%；P=0.83）或其他新生儿或产妇的次要结局。没有证据表明母体血糖控制对新生儿性别、胎龄、母体 BMI、使用倍他米松的指征、从倍他米松到分娩的时间、母体种族或民族、或新生儿性别有影响。此外，采用意向性治疗分析的敏感性分析结果不变。
在接受晚期早产儿倍他米松治疗的大多数非糖尿病产妇中观察到母体高血糖。然而，母体血糖控制并不能改善胎儿代谢状态、新生儿低血糖或其他新生儿或产妇结局。因此，在接受晚期早产儿类固醇治疗的非糖尿病产妇中，母体血糖监测和治疗似乎没有益处。
