Short-term variation of the fetal heart rate as a marker of intraamniotic infection in pregnancies with preterm prelabor rupture of membranes: a historical cohort study

Figures & data

Figure 1. Directed acyclic graph showing the relationship between exposure, outcome, and covariates. Green arrows: causal pathways; pink arrows: biasing pathways; black pathways: neither causal nor biasing pathways, but adjusting for baseline frequency makes the pathway through fetal sex a causal pathway; pink circles: confounders (common causes of exposure and outcome); blue circles: covariates affecting the outcome; green circle: covariate affecting exposure. Abbreviations: BMI, body mass index; CTG, cardiotocography.

Figure 2. Flow chart showing study population selection. Abbreviations: PPROM, preterm prelabor rupture of membranes; CTG, cardiotocography.

Table 1. Maternal and neonatal characteristics, and comparison of neonates exposed and non-exposed to intraamniotic infection, using early-onset neonatal sepsis as a proxy for intraamniotic infection.

	No intraamniotic infection (n = 651)	Intraamniotic infection (n = 27)	p value^a
Maternal characteristics
Age (years)	33 (29–36)	32 (28–35)	0.333
Body mass index (kg/m^2)^b	23.1 (21.2–26.7)	25.2 (22.3–28.2)	0.102
Smoking^b	6.0%	16.0%	0.044^*
Parity: 0, 1, 2+	30.3%, 44.9%, 24.9%	37.0%, 37.0%, 26.0%	0.685
Gestational age at PPROM (weeks)	30.9 (27.7–32.6)	30.6 (24.9–32.7)	0.621
Interval from PPROM to birth (days)	3.9 (1.8–9.4)	3.3 (2.1–5.8)	0.595
Diabetes^c	3.7%	14.8%	0.004*
Hypertension^c	1.1%	0.0%	0.588
Preeclampsia	0,8%	3.7%	0.111
Lag time from the last corticosteroid administration to the last 30 min CTG trace (hours)	86.0 (24.0–245.1)	54.1 (24.6–311.3)	0.863
Lag time from the last 30 min CTG trace to birth (hours)	6.4 (3.1–12.8)	4.1 (1.5–13.4)	0.162
Mean baseline frequency in the last 30 min CTG trace before start of labor	145.4 (138.3–152.0)	145.1 (137.4–164.0)	0.192
Neonatal characteristics
Gestational age at birth (weeks)	32.0 (29.4–33.1)	31.6 (26.0–33.3)	0.320
Birthweight (grams)	1762 (1332–2126)	1589 (990–2030)	0.284
Female gender	44.7%	29.6%	0.122
Small for gestational age^d	10.0%	11.1%	0.849
pH in umbilical artery at birth	7.31 (7.25–7.35)	7.25 (7.23–7.35)	0.533
Base deficit in umbilical artery at birth (mmol/L)	2.6 (0.9–5.0)	4.0 (1.3–6.0)	0.375
Apgar scores at 1 min	8 (6–9)	6 (4–9)	0.003*
Apgar scores at 5 min	9 (8–10)	8 (6–10)	0.017*
Apgar scores at 10 min	10 (9–10)	10 (8–10)	0.455
Neonatal death within 28 days from birth	1.2%	0%	0.562

Data are presented as medians with interquartile ranges, or as percentages.

^* Indicates p < 0.05.

Abbreviations: PPROM, preterm prelabor rupture of membranes; CTG, cardiotocography.

^a Mann-Whitney U test and Pearsons Chi2-test were used where appropriate.

^b Registered at first visit to maternity care.

^c Existing before pregnancy or diagnosed during pregnancy.

^d Defined as ^birth weight below 2 standard deviations from mean birth weight at current gestational age.

Table 2. Mean short-term variation (STV) in fetuses non-exposed and exposed to intraamniotic infection (IAI), with early-onset neonatal sepsis (EONS) as a proxy for IAI, with standard deviation (SD).

	N exposed (% of total)	Mean STV (SD) in the last CTG trace before birth		Absolute difference in STV in ms (95% CI)	p value	Relative difference in STV in % (95% CI)	p value
		No intraamniotic infection	Intraamniotic infection	Unadjusted comparison of non-IAI and IAI
IAI (all EONS as proxy)	27 (4.0)	6.62 (2.69)	5.25 (1.88)	−1.37 (−2.40, −0.34)	0.009^*	−20.5 (−31.0, −8.5)	0.002*
IAI (only confirmed EONS as proxy)	12 (1.8)		4.96 (4.96)	−1.65 (−3.19, −0.12)	0.034*	−23.5 (−37.9, −5.7)	0.012*
				Adjusted comparison of non-IAI and IAI, model 1^a
IAI (all EONS as proxy)				−1.34 (−2.38, −0.30)	0.012*	−20.5 (−31.1, −8.3)	0.002*
IAI (only confirmed EONS as proxy)				−1.63 (−3.17, −0.09)	0.038*	−23.4 (−37.9, −5.6)	0.013*
				Adjusted comparison of non-IAI and IAI, model 2^b
IAI (all EONS as proxy)				−0.18 (−1.00–0.64)	0.671	−6.3 (−16.3–4.8)	0.252
IAI (only confirmed EONS as proxy)				−0.54 (−1.74–0.65)	0.373	−11.4 (−24.7–4.4)	0.148

The absolute difference in ms, relative difference in percentage, and 95% CI are shown. Adjusted results are according to two models. Confirmed EONS: positive blood culture.

^* Indicates p < 0.05.

^a Adjusted for smoking and diabetes.

^b Adjusted for smoking, diabetes, the duration between PPROM and birth, the baseline frequency, neonatal gender.

Table 3. Mean short-term variation (STV) in fetuses non-exposed and exposed to intraamniotic infection (IAI), with acute histologic chorioamnionitis (HCA) and a fetal inflammatory response (FIR) as proxies for IAI, shown with standard deviation (SD).

	N exposed (% of total)	Mean STV (SD) in the last CTG trace before birth		Absolute difference in STV in ms (95% CI)	p value	Relative difference in STV in % (95% CI)	p value
		No intraamniotic infection	Intraamniotic infection	Unadjusted comparison of non-IAI and IAI
IAI (with HCA as proxy)	236 (64.7)	6.63 (2.19)	5.74 (2.12)	−0.89 (−1.35, −0.43)	<0.001^*	−13.7 (−19.8, −7.2)	<0.001*
IAI (with FIR as proxy)	212 (58.1)	6.66 (2.19)	5.61 (2.08)	−1.04 (−1.49, −0.60)	<0.001*	−15.8 (−21.5, −9.6)	<0.001*
				Adjusted comparison of non-IAI and IAI, model 1^a
IAI (with HCA as proxy)				−0.89 (−1.35, −0.42)	<0.001*	−13.8 (−19.9, −7.2)	<0.001*
IAI (with FIR as proxy)				−1.05 (−1.50, −0.60)	<0.001*	−16.0 (−21.8, −9.9)	<0.001*
				Adjusted comparison of non-IAI and IAI, model 2^b
IAI (with HCA as proxy)				−0.21 (−0.61, 0.18)	0.2889	−3.9 (−9.7, 2.2)	0.2077
IAI (with FIR as proxy)				−0.21 (−0.60, 0.18)	0.2909	−4.0 (−9.7, 2.1)	0.1963

The absolute difference in ms, relative difference in percentage, and 95% CI are shown. Adjusted results are according to two models.

^* Indicates p < 0.05.

^a Adjusted for smoking and diabetes.

^b Adjusted for smoking, diabetes, the duration between PPROM and birth, the baseline frequency, neonatal sex.

Data availability statement

The participants of this study did not give written consent for their data to be shared publicly, so due to the sensitive nature of the research supporting data is not available.