This is a prospective study. Data were systematically collected from the Department of Obstetrics and Gynecology of The Second Affiliated Hospital of Wenzhou Medical University from September 2019 to September 2020 (clinicaltrials.gov: NCT04369313). Ethics approval was obtained from our hospital (approval number: L-2019-13).
All qualified pregnant women delivered in our hospital underwent prenatal screening. Pregnant women with Rhesus negative type, abnormal liver function, hypertension, history of smoking and drug abuse, or abnormal amniotic fluid volume, preterm birth, placenta previa and other pregnancy complications were excluded. In addition, newborns also were excluded if they had a birthweight <2500g, a Apgar score ≤7 at 1 min or 5 min, meconium-stained amniotic fluid, neonatal malformation, or requiring neonatal resuscitation. Based on glucose test results and previous medical history, eligible subjects were divided into two groups, normal pregnant women group without any pregnancy complications and diabetic pregnant women group including pre-gestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM).
For pregnant women without risk factors for gestational diabetes mellitus, oral glucose tolerance test (OGTT) was performed at 24-28 weeks of gestation. The diagnostic criteria for GDM were fasting plasma glucose (FPG) ≥ 5.1 mmol/L, or 1 hour (h) plasma glucose ≥ 10.0mmol/L, or 2 h plasma glucose ≥ 8.5 mmol/L. And the FPG and HbA1C were tested at the first antenatal examination for pregnant women with risk factors for GDM. FPG ≥ 7.0 mmol/L or HbA1C ≥ 6.5% was considered as PGDM. Criteria for good blood glucose control in the third trimester are the glycosylated hemoglobin (HbA1c) below 6.0% and blood glucose levels below 6.7 mmol/L at 120 minutes postprandial.
In our pre-experiments, group sample sizes of 52 and 52 achieve 90% power to detect a difference of 0.9 between the null hypothesis that both group means are 8.3 and the alternative hypothesis that the mean of group 2 is 7.4 with estimated group standard deviations of 1.4 and 1.4 and with a significance level (alpha) of 0.05000 using a two-sided two-sample t-test. Considering that unqualified cases needed to be excluded from the trial, we increased the number of cases of every group from 52 to 70. Finally, the number of cases in diabetes pregnancy groups is 140 and that in normal pregnancy group is 140.
Consecutive pregnant women each in the group without pregnancy complications and in the group with diabetes were included according to the criteria. All the enrolled women were 18-44 years old, singleton gestation at 37 and 41 weeks plus 6 days, and signed informed consent prenatally. The women were randomly allocated to either the immediate cord clamping (ICC) or the later cord clamping (LCC) subgroup in a 1:1 ratio. Each case was identified by a unique assignment number from a computer-generated random-number list. An opaque envelope containing A or B card. According to the random sequence, the women who drew card A were assigned to the ICC group and the women who drew card B were assigned to the LCC group.
Due to the characteristics of the intervention, the mothers, the researchers performing the intervention and the assistants recording the clamping time were not masked to allocation procedure, while the physicians who measured percutaneous bilirubin value, neonatologists deciding to perform phototherapy and the statisticians conducting the data analysis were blinded to treatment.
In this study, the clamping time in the ICC group was less than 15 s after birth, while it was more than 30 s in the LCC group. Before the umbilical cord was clamped, neonates with vaginal delivery were placed on the mothers' abdomen and neonates with cesarean section were placed on the mothers' lap. Performing umbilical cord clamping on the newborn according to the original grouping and the clamping time was recorded by an assistant. The surgery was performed by obstetricians with the same surgical skills. In addition, when the mother or newborn needs resuscitation, the proper time for umbilical cord clamping is applied and the trial should be stopped immediately.
Basic demographic characteristics of the mother and newborn were recorded including mother's age, BMI, mode of delivery, gravidity, parity, gestational age, birthweight, fetal sex and Apgar scores at 1 min and 5 min. Neonatal bilirubin levels on days 2-4 and neonatal phototherapy rate were also documented. Neonatal percutaneous bilirubin levels were measured by the same physician using a unified TCB device (JM-103, Konica Minolta, Japan) at 8:00 a.m. every day. Whether the newborn undergo phototherapy was decided by the clinical neonatologist according to the recommendation of our unit.
Data were analyzed using SPSS version 20 (IBM, Armonk, NY, USA). Normally distributed variables were presented as mean ± standard deviation and analyzed by Student's t test or one-way ANOVA. Nonnormally distributed variables were expressed as median and interquartile range and analyzed by Mann-Whitney U test. Categorical variables were presented as number (%) and analyzed by Pearson's Chi-square test. The participants were stratified according to the degree of maternal glycemic control. A p value <0.05 was considered statistically significant.