Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study

While diabetes during pregnancy is associated with a significant risk of adverse perinatal outcomes, there is no consensus on the risks of adverse outcomes resulting from abnormal glucose levels below the established threshold for gestational diabetes. In response to this controversy, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study was established to clarify unanswered questions concerning the association of glucose with risks of adverse pregnancy outcomes.

The prospective, observational HAPO Study enrolled 23,316 pregnant women who had no prior diagnosis of diabetes during or antedating pregnancy. Participants underwent a standard 75 g 2-hour oral glucose tolerance test (OGTT) between 24 and 32 weeks’ gestation. Neonatal anthropometrics were obtained following delivery, and follow-up data, including hospital readmissions, were collected at 4-6 weeks post-delivery. The primary outcome measures assessed in relation to maternal glycemia included primary cesarean delivery, increased birthweight (defined as > 90th percentile for gestational age), neonatal hypoglycemia, and fetal hyperinsulinism. The study found that increased maternal glycemia was associated with both birthweight and cord serum C-peptide > 90th percentile. Greater maternal glucose levels were also associated with increased risk of primary cesarean delivery and clinical neonatal hypoglycemia.

Subsequent to the conclusion of the HAPO Study, a follow-up study (HAPO-FUS) was initiated to determine whether elevated blood sugar during pregnancy, below the threshold for gestational diabetes, influences either development of type 2 diabetes mellitus in mothers or adiposity and disorders of glucose metabolism in offspring at 8-12 years of age. The HAPO Follow-Up Study enrolled 4800 mother-child pairs who originally participated in the HAPO Study. Mothers and children were required to undergo a single study visit for measurement of height, weight, blood pressure, body fat, insulin, and blood sugar and lipid levels. The primary outcome measures assessed in relation to maternal glycemia during pregnancy included development of diabetes in mothers, and obesity and altered glucose metabolism in children, as well as other metabolic abnormalities in both mothers and offspring.

尽管妊娠期糖尿病与显著的不良围产儿结局风险相关，但针对低于妊娠期糖尿病（gestational diabetes）诊断阈值的异常血糖水平所引发的不良结局风险，目前尚无共识。为解决这一争议，高血糖与不良妊娠结局（Hyperglycemia and Adverse Pregnancy Outcome, HAPO）研究应运而生，旨在阐明与血糖水平和不良妊娠结局风险相关的尚未解答的问题。

本项前瞻性观察性HAPO研究共纳入23316名妊娠期间及妊娠前未被诊断为糖尿病的孕妇。受试者在妊娠24至32周期间接受标准75g 2小时口服葡萄糖耐量试验（oral glucose tolerance test, OGTT）。分娩后采集新生儿人体测量学数据，并于产后4至6周收集包括再次住院在内的随访数据。针对孕妇血糖水平所评估的主要结局指标包括：首次剖宫产、出生体重超标（定义为胎龄校正后大于第90百分位数）、新生儿低血糖以及胎儿高胰岛素血症。研究结果显示，孕妇血糖升高与出生体重及脐血C肽大于第90百分位数均存在关联；孕妇血糖水平越高，首次剖宫产及临床新生儿低血糖的发生风险也越高。

在HAPO研究结束后，后续随访研究（HAPO-FUS）随即启动，旨在明确低于妊娠期糖尿病诊断阈值的妊娠期血糖升高，是否会对母亲发生2型糖尿病（type 2 diabetes mellitus）的风险，以及后代在8至12岁时的肥胖和糖代谢紊乱情况产生影响。HAPO随访研究共纳入4800对曾参与原始HAPO研究的母婴对。所有母亲及儿童均需接受单次研究随访，测量身高、体重、血压、体脂、胰岛素、血糖及血脂水平。针对孕期孕妇血糖水平所评估的主要结局指标包括：母亲发生糖尿病、儿童肥胖及糖代谢异常，以及母婴双方的其他代谢异常。