Study population
The cohort consisted of 5150 singleton childbirths with continuously monitored CTG tracings during the last two hours of labor with ≥ 33 weeks of gestation at the Maternity Hospital, Helsinki University Hospital (HUS) between January 1 and December 31, 2012. In the Helsinki metropolitan area, the Maternity Hospital took care of low-risk childbirths, excluding, for example, preterm births < 33 weeks of gestation, childbirths of women with severe preeclampsia or type 1 diabetes, and fetuses with severe intrauterine growth restriction. The one-year obstetric cohort is the same as in our recent report on term deliveries, except for the inclusion of preterm (from 33.0 to 36.9 weeks of gestation) deliveries in the present study [11]. All women in the cohort were in the active phase of labor with regular uterine contractions. Preterm pregnancies with < 33 weeks of gestation, non-cephalic presentations, elective cesarean delivery without labor contractions, major congenital malformations, and cases with missing CTG registration or missing UA blood gas results were excluded from the study cohort (Fig. 1). FHR was recorded via a scalp electrode in 91.1% of the cases.
According to the OGTT, the cohort was divided into three groups: GDM, normal OGTT, and no OGTT performed (Fig. 1). The maternal and delivery-related characteristics of the three groups are presented in Table 1.
Table 1 Maternal and delivery-related characteristics when GDM is present or absent, or without OGTT performed All women were screened according to the Finnish National Current Care guidelines for gestational diabetes mellitus [4, 14]. The guidelines recommend that all women should be screened for GDM, excluding those with a very low risk (a primipara ≤ 25 years old with a body mass index (BMI) < 25 kg/m2, and without a family history of type 2 diabetes, or a parous woman < 40 years old with a BMI < 25 kg/m2, without a family history of type 2 diabetes and without previous GDM or fetal macrosomia, i.e., birth weight z-score > 2.0 SD-units) [14]. A 2-h OGTT for screening of GDM with 75 g glucose was performed at 24–28 weeks of gestation with the following cut-off values: fasting ≥ 5.3 mmol/l, 1 h value ≥ 10.0 mmol/l, and 2 h value ≥ 8.6 mmol/l. A single abnormal value was diagnostic for GDM [14].
Data sources
The CTGs were recorded using Avalon® FM40 and FM50 (Philips Healthcare, Andover, MA, USA) fetal monitors. All CTG recordings were stored in visual and electronic forms in the Milou® (Medexa, Limhamn, Sweden) CTG database at the Data Analysis and Management Department of HUS. After delivery, CTG recordings were coded and printed on paper for two experienced perinatologists for interpretation. The clinical data were collected from electronic obstetric patient records (Obstetrix®, Obstetrix Medical Group, Englewood, CO, USA). The results of the oral glucose tolerance test (OGTT) were obtained from the HUS Weblab Clinical® laboratory information system.
Evaluation of intrapartum CTG recordings
Two experienced perinatologists (S.S. and K.T.) evaluated the CTG recordings independently and without knowing the maternal, fetal or neonatal data, and perinatal outcomes in order to assess the following CTG changes: ZigZag pattern, saltatory pattern, late decelerations, episodes of bradycardia and tachycardia, reduced FHR variability, and uterine tachysystole. Only concordant CTG changes between the evaluators were used in the analyses. The findings were classified according to the FIGO (The International Federation of Gynecology and Obstetrics) guidelines on intrapartum fetal monitoring with the exception the ZigZag pattern (see below) [15].
Normal baseline FHR was defined as a baseline between 110 and 160 bpm. Normal FHR variability was defined as baseline amplitude changes of 5–25 bpm. The ZigZag FHR pattern was defined as FHR baseline amplitude changes of > 25 bpm with a duration of 2–30 min [11]. The definition of the ZigZag pattern differs from the saltatory pattern in its duration and uniformity of the trace. The saltatory pattern was defined as FHR baseline amplitude changes of > 25 bpm and a duration of > 30 min. Late decelerations were defined as U-shaped decreases of FHR of > 15 bpm occurring late in relation to uterine contractions. In the presence of a tracing without accelerations and with reduced variability, the definition of late decelerations included also those with an amplitude of 10–15 bpm. Tachycardia was defined as a baseline frequency above 160 bpm lasting for more than 10 min. According to the FIGO guideline, FHR values between 100 and 110 bpm may occur in normal fetuses, especially in postdate pregnancies. Thus, in the present study, a bradycardia episode was defined as a baseline frequency below 100 bpm lasting for more than 3 min. The reduced variability was defined as an amplitude below 5 bpm for more than 10 min and that of uterine tachysystole as the occurrence of more than 5 contractions during a 10 min period. Figure 2 shows a CTG recording with ZigZag pattern followed by late decelerations.
Maternal and delivery-related variables
The following maternal and delivery-related variables were determined: maternal age, prepregnancy BMI, ethnicity, mode of delivery, type of onset of labor (spontaneous or induction), oxytocin augmentation, gestational age, family history of type 2 diabetes, parity, present or previous GDM, previous fetal macrosomia, preeclampsia, maternal fever ≥ 38.0 °C, and smoking.
Fetal and neonatal variables
The following fetal and neonatal variables were determined: gestational age at delivery, fetal sex, birth weight z-score, umbilical artery (UA) pH, base excess (BE), and pO2, Apgar scores at 1 and 5 min, need for intubation and resuscitation, neonatal intensive care unit (NICU) admission, and neonatal encephalopathy. According to the hospital`s general practice, UA blood was routinely collected from a double-clamped cord for pH and blood gas analyses in all childbirths. Fetal asphyxia was defined as UA pH < 7.10 and/or UA BE < -12.0 meq/L and/or 5-min Apgar scores < 7 [16, 17]. Neonatal respiratory distress was defined as the need for continuous positive airway pressure (CPAP) delivered using a T-piece-based infant resuscitator Neopuff® (Fisher & Paykel Healthcare Limited, Auckland, New Zealand) and/or intubation.
Data analyses
We analyzed continuous variables by Analysis of variance (ANOVA), Kruskal–Wallis test and Mann–Whitney U-test. Pearson`s Chi-square and Fisher's Exact Probability test were used for categorical variables. All tests were two-sided. Values of P < 0.05 were considered statistically significant.
Logistic regression analysis was used to evaluate whether GDM was associated with hypoxia-related CTG changes when the models included parity, type of onset of labor (spontaneous or induction), oxytocin augmentation, obesity (prepregnancy BMI ≥ 30.0 kg/m2), gestational age at delivery (preterm < 37 weeks, term, or postterm ≥ 42 weeks of gestation), maternal age ≥ 35 years, preeclampsia, maternal fever ≥ 38.0 °C, smoking, fetal sex, and fetal macrosomia (birthweight z-score > 2.0 SD-units). The logistic regression analysis was performed by R version 3.6.0 and the odds ratios (OR) and 95% confidence intervals (CI) were estimated by fitting logistic regression models.