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M A T E R N O - F E T A L M E D I C I N E

Correlation of myometrial thickness and the latency intervalof women with preterm premature rupture of the membranes

Lina AtarJavdan • Zahra Khazaeipour •

Fatemeh Shahbazi

Received: 19 September 2010 / Accepted: 11 January 2011/ Published online: 5 February 2011

Springer-Verlag 2011

Abstract

Objective To verify the hypothesis that a correlationexists between myometrial thickness (MT) and latency

interval (LI) in patients with preterm premature rupture of

membrane (PPROM).

Method Myometrial thickness was measured ultrasono-

graphically at the mid-anterior (MA), fundal, and posterior

parts of the uterus of pregnant women in the following

groups: PPROM [n = 45, mean (range), gestational age

(GA): 28.6 weeks (w) (24.0–33.0 w)], preterm nonlabor

control group (P-CTR) [n = 20, GA: 29.5 w (25.0–

32.0 w)] and term nonlabor control (T-CTR) [n = 27, GA:

38.4 w (37.0–41.0 w)].

Results There was a positive correlation between LI and

fundal MT (r = 0.34, P = 0.02), mid-MT (r = 0.47,

P = 0.001) and LUS (r = 0.74, P = 0.001). The results

were similar in the group of \30 w of GA, but in the group

of C30 w of GA, there was no association. The LUS MT

has more area under the ROC curve than MA MT and

fundal MT for prediction of LI of B8 days.

Conclusion Significant positive correlation between LI

and MT in patients with PPROM may result in a better

decision for taking care of infants of preterm birth.

Keywords PPROM Myometrial thickness

Latency interval

Pregnancy

Preterm birth

Introduction

Premature rupture of membranes (PROM) is defined as the

rupture of membranes before delivery signs are evidenced. It

has been reported that prevalence of PROM is 6–10%, of

which 80% happened after week 37 of pregnancy [1]. PROM

followed by pretermdelivery is the most prevalent reason for

prenatal morbidity and mortality in the USA [2, 3]. If PROM

happens before week 37 of pregnancy, it is called preterm-

premature rupture of membrane (PPROM). PPROM has

many reasons, but infection is the most common reason [4].

With PROM, morbidity and mortality increases. The major

risk is intra-uterine infection that causes PROM directly. By

reduction of pregnancy term, fetal morbidity and demise

increase as a result of preterm birth and fetal abnormality.

Despite the wide care during birth and increasing access to

infant intensive care unit, preterm birth and low weight of

infants is responsible for 75% of infant mortality [5]. Based

on the hypothesis that even one small delay during PPROM

to delivery is useful for the fetus, treatment of pregnancy

with PPROM occurred, in the absence of clinical symptoms

or experimental chorioamniotic [4].

Researchers have been investigating the factors that

cause preterm delivery such as digital examination of the

cervix, monitoring of uterine contraction at home and LUS

thickness [6–9]. Digital investigation of cervix and fre-

quency of uterine contractions for prediction has less value

[7]. Furthermore, digital investigation of cervix may

increase the risk of progressive infection [10].

It has been investigated that the clinical predictors of

early preterm delivery (PTD) including cervical change,

L. AtarJavdan

Women Hospital (Mirza Kuchakkhan Women Hospital),

Tehran University of Medical Sciences, Karimkhan Zand Street,

Tehran, Iran

Z. Khazaeipour (&) F. Shahbazi

Research Deputy of Imam Khomeini Hospital Complex,

Tehran University of Medical Sciences, Keshavarz Blvd,

14155-6388 Tehran, Iran

e-mail: [email protected]

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Arch Gynecol Obstet (2011) 284:1339–1343

DOI 10.1007/s00404-011-1841-x

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uterine contractions, vaginal bleeding and the birth activity

of fetus were neither sensitive nor specific. These pre-

monitory symptoms are only exact at the late stages in the

pathogenic procedure [11].

A few studies have investigated the correlation of

myometrial thickness (MT) with PPROM and delivery time

[12], but this correlation has not been well verified. Veri-

fication of the correlation between MT and longer latencyinterval of women with PPROM may assist clinicians in

providing consultation regarding management for women

presenting with PPROM and may result in a better decision

for taking care of infants after preterm birth.

Our aims were to study the correlation of MT and

latency interval (LI) and prediction ofLI and delivery, in

patients with PPROM.

Materials and methods

Study design

A prospective cohort study was performed in 92 pregnant

women enrolled in the following groups: exposure group

[n = 45, PPROM, gestation age (GA): 24–33 weeks (w)],

the control group, which consisted of healthy pregnant

women [preterm nonlabor control group (P-CTR, n = 20,

GA = 25–32) and term nonlabor control group (T-CTR,

n = 27, GA = 37–41)] referred to Mirza Kochakkhan

hospital between 2007 and 2009. The patients referred to

the hospital were aged 22–37 years, but the only inclusion

criterion was singleton pregnancy.

Fetal anomalies, asymmetric intrauterine growth retar-

dation (IUGR), weight\10% for GA based on ultrasono-

graphic evaluation, placenta abnormalities (low lying

placenta, abruptio placentae), degree of implantation of

placenta within the uterus, cervical cerclage in the absence

of sign and symptom of chorioamnionitis, fever more than

38C, fetal tachycardia and fetal heart beat abnormalities

(late deceleration or variable of heart beat) were excluded.

All the women who had the input qualifications were asked

to participate in this research and signed the informed

consent.

For diagnosis of PROM, both positive fern and nitrazine

tests at the time of admission by sterile speculum exami-

nation ‘‘to see amniotic fluid (AF)’’ were performed.

Ultrasonographic evaluation for women with PROM was

performed during 12 h.

All scans on women in the threatened PROM group

were performed abdominally via sonographic equipment

(focuda) using transabdominal curvilinear probe with a

3.5-MHz frequency. The amniotic fluid index (AFI) was

calculated and for oligohydramnios AFI\ 5 cm was

considered. With sonographic evaluation, myometrium was

identified as the echo homogeneous layer between the

serosa and the decidua.

MT was measured at three different parts: at the lower

uterine segment (LUS, 2 cm above the urinary bladder

reflection), mid-anterior (MA, with probe, 1 cm above the

patient’s navel) and fundal (beginning of the curved part of

the uterus) wall. Fundal thickness of the uterine body was

measured by placing the probe scans above the uterinefundus and all the bent parts of the uterine body were seen.

Each scan was measured separately; at least three mea-

surements of each part were performed and mean ± SE

was obtained. Both sonography and measurements were

performed by one researcher. Reliability of measurements

in the intraobserver was 93%.

Treatments of patients were performed by the treatment

group. All the patients received corticosteroid for fetal lung

maturation, and antibiotics (ampicillin/erythromycin)

according to the PPROM protocol [13]: intravenous

ampicillin (2-g dose every 6 h) and erythromycin (250-mg

dose every 6 h) for 48 h, followed by oral amoxicillin(250-mg dose every 8 h), erythromycin base (333-mg dose

every 8 h) for 5 days and intramuscular corticosteroids

(12 dose, every 24 h) for 2 days.

Patients \32 weeks received corticosteroid for lung

maturation and antibiotics (ampicillin/erythromycin). To

investigate the fetal abnormality or uterus contraction,

women were monitored daily by cardiotocography method.

Sonography (two times a week) and NST (daily) were

performed.

Data analysis was performed with the SPSS software

(SPSS Inc., Chicago, IL, USA). Normal distribution of data

were analyzed by one-sample Kolmogorov–Smirnov test. To

compare three group means, Kruskal–Wallis test and

ANOVA wereused, and for two group means Mann–Whitney

U test was used. Spearman’s q was used to identify correla-

tion. Quantitative variables were shown by mean ± SD.

Differences were considered significant when P\0.05.

Ethical issues

This research was based on Helsinki principle’s declara-

tions. Signed informed consent was obtained from each

patient and it was ensured that there was no loss or harm to

the patients.

All the information from the patients was kept

confidential.

Results

The mean of age for PPROM was 27.9 ± 4.7 years

(22–37 years); the mean for GA based on LMP was

28.6 ± 3.3 w (24–33 w).

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The mean values of GA based on ultrasonography in the

first trimester in group T-CTR (37–41), group P-CTR

(25–32) and group PPROM (24–34) were 38.4 ± 1.27,

29.5 ± 2.23 and 28.6 ± 3.2, respectively (P = 0.002).

There were significant differences between T-CTR and

P-CTR (P = 0.001) and between T-CTR and PPROM

(P = 0.001).

The mean value of AF in the PPROM group (2–14 cm)was 5.9 ± 3.22, of which gravid 1, gravid 2, gravid 3,

gravid 4 and gravid 5 had 46.7, 26.7, 17.8, 8.9 and 8/9%,

respectively.

As much as 55.6% of them were without miscarriages

and 28.9% had miscarriage only once; 77.8% were without

a live birth at delivery, 13.3% with one live birth, 8.9%

with two live births, and 2.2% with one stillborn.

Regarding fetal presentation, 17.8% were breech pre-

sentations (n = 8) and 82.2% were cephalic presentations

(n = 37). Regarding placenta position, 20% were of fundal

position (n = 9), 33.3% of posterior position [15] and

46.7% of anterior position (n = 21). Demographic andclinical characteristics and the correlation between MT at

three different parts of the uterus (fundal, mid-anterior and

LUS) in T-CTR, P-CTR and PPROM groups are presented

in Table 1. There was no significant correlation between LI

and AF, but positive correlation between LI and MT at

three different parts as shown as follows: LUS (r = 0.74,

P = 0.001), MA (r = 0.47, P = 0.001), fundal (r = 0.34,

P = 0.02). In the group of GA B 30 w, no significant

correlation between LI and AF (r = 0.15, P = 0.4) was

found. Correlations between LI and MT were: MA,

r = 0.36, P = 0.049; LUS, r = 0.69, P\ 0.0001; and

fundal, r = 0.3, P = 0.08. In the group of GA[ 30 w, nosignificant correlation between any of the variables was

found. The correlations between LI with AF and MT at

three different parts in group 1 (AF B 5) and group 2

(AF[ 5) are presented in Table 2.

Figure 1 shows that for the latency interval of B8 days,

area under curve of LUS MT (0.92) was more than fundal

MT (0.65) and MA MT (0.70).

The sensitivity, specificity and thickness of MT in three

different parts of the uterus for LI of B8 days are presented

in Table 3.

Discussion

Based on sonography, GA showed significant differences

between the three groups (P = 0.002) and two groups as

Table 1 Demographic and clinical characteristics and comparison between myometrial thickness at three different parts (fundal, mid-anterior

and LUS) in T-CTR, P-CTR and PPROM groups

Myometrial thickness T-CTR P-CTR PPROM P value

Age

Mean ± SD 28.3 ± 4.04 27.3 ± 4.96 27.9 ± 4.7 0.7

Median (range) 28 (23–35) 25 (22–37) 27 (22–37)

Gestational age (based on sonography)

Mean ± SD 38.4 ± 1.28 29.5 ± 2.23 28.7 ± 3.23 \0.0001

Median (range) 38 (37–41) 30 (25–32) 29 (24–34)

Fundal

Mean ± SD 8.3 ± 1.04 7.7 ± 1.11 8.2 ± 3.44 0.1

Median (range) 8.6 (6–10) 7.6 (5–10) 8 (2–19)

Mid-anterior

Mean ± SD 9 ± 1.66 7.7 ± 1.53 8.7 ± 4.37 0.04

0.002*

Median (range) 8.8 (6–14) 7.2 (5–12) 8 (2–22) 0.2

LUSMean ± SD 5.6 ± 1.35 6.4 ± 0.76 8.1 ± 4.25 0.002

0.006

Median (range) 5.3 (4.2–9) 6.5 (4–7.5) 7 (3.2–22) 0.002§

0.1||

* Comparison of P-CTR with T-CTR Comparison of T-CTR with PPROM Comparison of P-CTR with T-CTR§ Comparison of T-CTR with PPROM|| Comparison of P-CTR with PPROM

Arch Gynecol Obstet (2011) 284:1339–1343 1341

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well (T-CTR and P-CTR, P = 0.001) (T-CTR and

PPROM, P = 0.001).

In contrast to Buhimschi results, which showed that the

fundal part of the myometrial of the PPROM group was

thicker than the other groups (P-CTR, P\ 0.001 and

T-CTR, P = 0.015) [12], we found that there were no

differences for fundal MT in these three groups.Buhimschi results showed that myometrium at the MA

part was thicker in the PPROM group than in the other

groups (P-CTR, P\ 0.001; and T-CTR, P = 0.025).

Similarly our results showed significant differences

(P = 0.04) for the MA MT of the three groups and

between two groups as well (T-CTR and P-CTR,

P = 0.002). However, dissimilar to Buhimschi results,

myometrium in the T-CTR was thicker than that in the

others (P-CTR, P\0.001; and T-CTR, P = 0.025).

LUS MT mean values in T-CTR (4.2–9, 5.6 ± 1.35)

was less than P-CTR (4–7.5, 6.4 ± 0.76) and PPROM

(3.2–22, 8.1 ± 4.25 mm); P = 0.002.

Comparison of LI in GA B 30 w ( M = 8.5, Q1–Q3 =

4.7–11.2) with GA[ 30 w ( M = 7, Q1–Q3 = 3–10) did

not show significant differences (P = 0.1). A few reports

have shown inverse correlation between gestational age at

rupture of membranes with LI [14, 17]. Similar to this

former report, Test et al. [16] reported that the duration of

the LI was significantly longer among women with

PPROM before 34 weeks as compared to PPROM after

34 weeks of gestation (5.78 vs. 2.02 days; P\ 0.001).

Manuck et al. [15] also suggested that LI does not appear to

worsen outcomes in pregnancies that are complicated by

PPROM.

LI has no significant correlation with AF, but it has a

significant and positive correlation with MT at three dif-

ferent parts: fundal, MA and LUS (r = 0.74, P = 0.001).

Similar results were seen for the group of B30 w preg-

nancy, but in the group of [30 w of pregnancy there was

no association. LI in two groups of AF B 5 cm and

AF[ 5 cm also have positive and significant correlation

with MT (MA, Fundal and LUS), but no association with

AF was seen. In contrast to our results, Test et al. [16]

reported that prolonged latency was a significant risk factor

for chorioamnionitis. Aziz et al. [18] suggested that earlier

gestational age at the time of PPROM is associated with

longer LI, which, in turn, is not associated with increased

neonatal sepsis or chorioamnionitis.

Our results present a positive correlation between MT in

fundal and LI (r = 0.34, P = 0.02), which is similar to the

results of Buhimschi (r = 0.43, P = 0.02) [12]. LI was

8 days ( M = 8 days) and MT for the LUS part (0.92) was

more than that for fundal (0.65) and MA (0.70) parts

(Fig. 1).A fundal MT of 6.9 mm was 79% sensitive and 39%

specific for the identification of women whose LI was

8 days and an MA MT of 5.5 mm was 89% sensitive and

42% specific for the identification of women whose LI was

8 days, while Buhimschi showed that a fundal MT was less

than 12.1 mm, 93.7% sensitive and 63.6% specific for the

identification of women whose LI was 5 days. Buhimschi

concluded that a thick myometrium in nonlaboring patients

with PPROM is associated with longer latency interval.

ROC Curve

1 - Specificity

1.00.75.50.250.00

S e n s i t i v i t y

1.00

.75

.50

.25

0.00

Source of the Curve

Reference Line

LUS

Mid Anterior

Fundal

Fig. 1 ROC curve represents the thickness sensitivity and specificity

(diagonal segments are produced by ties) for three different parts

(fundal, midanterior and LUS) of uterus for the women whose latency

interval was 8 days

Table 3 Represent the information based on Fig. 1

Myometrial thickness Mid-anterior LUS Fundal

Sensitivity 89% 89% 79%Specificity 42% 85% 39%

Thickness 5.5 mm 7.35 mm 6.9 mm

Latency interval 8 8 8

Table 2 The correlation between latency interval with amniotic fluid and myometrial thickness at three different parts in group 1 (AF B 5) and

group 2 (AF[ 5)

Myometrial thickness Mid-anterior LUS Fundal Amniotic fluid

Latency interval (group 1) r = 0.37, P = 0.039 r = 0.8, P\0.0001 r = 0.2, P = 0.2 No correlation

Latency interval (group 2) r = 0.81, P = 0.0001 r = 0.739, P = 0.003 r = 0.53, P = 0.047 r = 0.78,

P = 0.001

1342 Arch Gynecol Obstet (2011) 284:1339–1343

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Sonographic evaluation of MT may represent an alternative

clinical tool for the prediction of a short LI in women with

PPROM [12].

Conflict of interest We declare that we have no conflict of interest.

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