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JOURNAL OF TROPICAL PEDIATRICS, VOL. 56, NO.

1, 2010

The Incidence Rate of Premature Rupture of Membranes and


its Influence on Fetal–neonatal Health: A Report From
Mainland China
by Jing Liu, Zhi-Chun Feng, and Jing Wu
Department of Neonatology & NICU, Bayi Children’s Hospital Affiliated with Beijing Military Region General Hospital, Beijing, China

Summary

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Premature rupture of membranes (PROM) is a common pregnancy complication and is associated with
significant risks of fetal and neonatal morbidity and mortality. However, there is a lack of data
concerning PROM in China. We investigated the incidence rate and analysed the influence of PROM
on fetal and neonatal health. This used data from five specialist hospitals and one general hospital in
mainland China. The total number of deliveries and the number of those complicated by PROM were
recorded between January 2003 and December 2007. The time from initiation of PROM until delivery
(latent period), the volume of amniotic fluid at delivery, fetal conditions and neonatal clinical conditions
were recorded. The results suggest that the incidence of PROM was 19.53% and it could influence
various aspects of the health of fetuses and neonates, including platelet parameters, erythrocyte
parameters, neonatal jaundice and myocardial injury.

Introduction respectively. Yang et al. [3] reported incidence rates


Premature rupture of membranes (PROM) is a of 30.1% and 17.8% for stillbirths and neonatal
common pregnancy complication and is associated deaths in presence of PROM, while 15.7% of
with significant risks of morbidity and mortality [1–4]. liveborn infants had pulmonary hypoplasia and
This complication is therefore of importance to 62.5% of which resulted in neonatal death. Gerards
perinatologists [5–8]. Getahun et al. [9] reported et al. [10] found that the incidence of pulmonary
that the incidences of PROM and acute and chronic hypoplasia was 33.3% in pregnancies complicated by
respiratory conditions were 5%, 2.1% and 9.5%, preterm PROM (PPROM), diagnosed on the basis of
clinical, radiological and/or pathological criteria.
Reports from the United States also linked health
risks to infants associated with PROM, with overall
rates of infant death of 11.6%, respiratory distress
Acknowledgements syndrome (RDS) 15.1%, assisted ventilation 25.9%
We thank the following doctors for providing some and neonatal seizures 0.2% in infants delivered
data: Dr Ya-Bin Yu from Beijing Obstetrics and following PROM [11]. Data from Nigeria (a devel-
Gynecology Hospital, Dr Xue-Feng Zhang from oping country) suggested that the incidence of
Beijing Haidian District Maternity and Infants’ PPROM was 29.7% and that the perinatal mortality
hospital, Dr Hong-Yan Lu from Zhanjiang in these infants was high (52%) at gestational ages of
Maternity and Infants’ hospital of Jiangsu Province, 28–30 weeks [12]. However, despite being the largest
Dr Shi-Wen Xia from Hubei Maternity and Infants’ developing country, China still lacks general data on
hospital, Dr Gui-Lian Qin from Qinhuangdao PROM. We therefore investigated the incidence and
Maternity and Infants’ hospital of Hebei Province. analysed the influences of PROM on fetal and
neonatal health, in order to develop a working
Funding protocol for improving fetal and neonatal health
Chinese Post-Doctoral Research Fund (20080431 after the occurrence of PROM.
405&200801041).
Materials and Methods
Correspondence: Pro. Zhi-Chun Feng, M.D., Department
of Neonatology & NICU, Bayi Children’s Hospital
Affiliated with Beijing Military Region General Hospital, Survey of the incidence of PROM in mainland China
5 Nanmen Cang, Dongcheng District, Beijing100700, Data were acquired from five specialist hospitals and
China. Tel: 86-10-66721786. E-mail: <Liujingbj@live.cn>. one general hospital, including Beijing Obstetrics and

ß The Author [2009]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org 36
doi:10.1093/tropej/fmp051 Advance Access Published on 19 June 2009
J. LIU ET AL.

Gynecology Hospital, Beijing Haidian District (1017 of 2596) of premature in-patients. The average
Maternity and Infants’ Hospital, Hubei Maternity birthweight of these infants was 1997.2  532.3 g
and Infants’ Hospital, Qinhuangdao Maternity and (range, 700–3900 g), and the average gestational age
Infants’ Hospital of Hebei Province, Zhanjiang was 32.4  2.01 weeks (range, 26–36 weeks).
Maternity and Infants’ Hospital of Jiangsu
Province and Beijing Military Region General Correlation between PROM and premature birth
Hospital. The total number of deliveries and the The incidence of premature birth was 11.2% (3265 of
number of those complicated by PROM were 29 143) in the PROM group and 5.96% (7150 of 120
recorded between January 2003 and December 057) in the non-PROM group (2 ¼ 1004.86,
2007. The time from initiation of PROM until P < 0.001).
delivery (latent period) and the volume of amniotic
fluid at delivery were also recorded simultaneously. The latent period
Among the 1422 infants with PROM, the latent

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period was <12 h in 142 cases (10.0%), 12 h in 469
The influence of PROM on fetal health cases (33.0%), 24 h in 178 cases (12.5%), 48 h in
Fetal conditions including birth weight, Apgar score 251 cases (17.7%), 72 h in 142 cases (10.0%), 96 h
after the first and fifth minutes and signs of fetal in 89 cases (6.3%), 1 week in 72 cases (5.0%), 2
distress were recorded. weeks in 58 cases (4.1%), 4 weeks in 20 cases
(1.41%) and the longest latent period was 12 weeks in
The influence of PROM on neonatal health one infant (0.07%).
Patients admitted to the Department of Neonatology
and NICU, Bayi Children’s Hospital Affiliated with Correlation between PROM and oligohydramnios
Beijing Military Region General Hospital between The overall incidence of oligohydramnios in patients
May 2007 and April 2008 were considered for with PROM was 12.8% (182 of 1422). The incidences
inclusion in this section of investigation. The of oligohydramnios were 25.9% (88/340) in the
presence or absence of PROM was recorded and group with a latent period 96 h and 11.3% (122 of
any diseases suffered by the infants, laboratory 1082) in the group with a latent period <96 h
parameters and results of blood bacteria cultures (2 ¼ 43.85; P < 0.001).
were recorded in patients with PROM.
Correlation between PROM and fetal distress
Statistical analysis The incidence rate of fetal distress was 15.1% (215 of
Data analysis was conducted using SPSS for 1422) in PROM infants, which was significantly
Windows (Release 12.0, SPSS, Chicago, IL). higher than that in non-PROM patients (8102/120
Analysis was performed using the 2 test, and 057, 6.7%) (2 ¼ 154.41, P < 0.001).
P < 0.05 was considered statistically significant.
Correlation between PROM and neonatal asphyxia
Birth asphyxia occurred in 214 infants in the PROM
Results group (214 of 1422, 15.0%) and in 355 patients in the
non-PROM group (355 of 5218, 6.8%) (2 ¼ 96.98,
Survey of the incidence of PROM P < 0.001).
A total of 29 143 pregnancies complicated by PROM
were identified among the 149 200 deliveries at the six Correlation between PROM and neonatal RDS
hospitals over the past 5 years (between January 2003 There were 139 cases of RDS among the 1422 PROM
and December 2007). The incidence of PROM in this patients (9.8%). Among the 139 RDS patients, there
population was therefore 19.53%. were 21 full-term infants and 118 premature infants.
The incidence of RDS was 5.2% (21 of 405) in full-
The proportion of in-patients accounted for by term infants and 11.6% (118 of 1017) in premature
PROM infants infants (2 ¼ 13.53, P < 0.001).
From May 2007 to April 2008, there were 6640
patients in our Department of Neonatology, of Correlation between PROM and neonatal
whom 1422 were patients with PROM (21.4%). infectious diseases
Among the 1422 patients with PROM, there were 405 Infectious diseases occurred in 445 of the 1422
full-term infants (218 males and 187 females) PROM infants (31.3%). Infections included infec-
accounting for 10.1% (405 of 4044) of full-term in- tious pneumonia (184 cases), septicemia (181 cases),
patients. The average birthweight of these infants was meningitis (33 cases), urinary tract infections (31
3204.2  586.9 g (range, 1335–5100 g), and the aver- cases) and others (16 cases). Blood cultures were
age gestational age was 38.8  1.24 weeks (range, performed in all the 1422 PROM infants, and
37–42 weeks). There were 1017 premature infants bacteria were detected in 179 patients, giving an
(622 males and 395 females) accounting for 39.2% overall positivity rate of 12.6%. The positivity rate

Journal of Tropical Pediatrics Vol. 56, No. 1 37


J. LIU ET AL.

TABLE 1
The changing in platelet parameter in full-term infants with and without PROM (x  s)

Groups n PLT (109/l) MPV (fl) PDW (%) PCT (%)

Without PROM 50 301.6  78.6 8.56  1.32 17.53  0.81 0.243  0.055
With PROM 100 264.7  87.0 9.69  1.09 11.54  2.28 0.255  0.088
t 2.44 4.81 22.92 0.71
P 0.017 0.000 0.000 0.48

TABLE 2
The changing in platelet parameter in premature infants with and without PROM (x  s)

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Groups n PLT (109/l) MPV (fl) PDW (%) PCT (%)

Without PROM 50 274.3  77.6 8.51  1.76 17.55  1.03 0.208  0.09
With PROM 100 233.2  70.0 9.84  1.03 11.35  1.71 0.241  0.06
t 3.16 5.06 27.41 2.25
P 0.002 0.000 0.000 0.028

TABLE 3
The changing in erythrocyte parameter in full-term infants with and without PROM (x  s)

Groups n RBC Hb Hct MCV MCH MCHC RDW

Without PROM 50 3.98  0.57 140.3  21.4 0.41  0.06 101.6  6.21 35.5  1.97 336.8  18.6 17.3  2.01
With PROM 100 4.25  0.85 154.6  33.1 0.46  0.09 107.8  6.36 37.4  2.04 347.6  11.6 17.2  1.91
t 2.29 3.19 4.20 5.78 5.55 3.76 0.30
P 0.023 0.002 0.000 0.000 0.000 0.0004 0.76

was 8.4% (34 of 405) in full-term infants and 14.3% (PCT,%) were recorded in 100 premature infants
(145 of 1017) in premature infants (2 ¼ 9.05, and 100 full-term infants with PROM, and these
P ¼ 0.003). The bacteria isolated included Gram- parameters were compared with those in 50 healthy
positive cocci in 82 cases (45.8%) and Gram-negative premature infants and 50 healthy full-term infants.
bacilli in 97 cases (54.2%) (no significant difference, The results are shown in Tables 1 and 2, respectively.
2 ¼ 0.820, P ¼ 0.365). Two epiphytes were also
found in this group of patients.
Changes in erythrocyte parameters in infants
with PROM
Changes in blood bilirubin levels in infants Erythrocyte parameters including red blood cell
with PROM count (RBC, 1012/l), hemoglobin (Hb, g/l), hema-
The average bilirubin blood levels in premature and tocrit (HCT, %), mean corpuscular volume (MCV,
full-term infants with PROM were 214.5  90.8 mmol/l fl), mean corpuscular Hb (MCH, pg), mean corpus-
(range, 45.4–697.0 mmol/l, 95% CI 205.9–223.1) and cular Hb concentration (MCHC, g/l) and red blood
209.7  120.6 mmol/l (range, 29.0–591.0 mmol/l, 95% cell volume distribution width (RDW, %) were
CI 190.3–229.1), respectively. Average blood bilir- recorded in 100 premature infants and 100 full-term
ubin levels were 220 mmol/l in 37.1% (377 of 1017) infants with PROM, and these parameters were
of premature infants and in 29.1% (118 of 405) of compared with those in 50 healthy premature infants
full-term infants. Hyperbilirubinemia was therefore and 50 healthy full-term infants. The results are
more common in premature infants with PROM. shown in Tables 3 and 4, respectively.

Changes in platelet parameters in infants with PROM Changes in cardiac muscle enzymes in infants
Platelet parameters including platelet count (PLT, with PROM
109/l), mean platelet volume (MPV, fl), platelet Cardiac muscle enzymes including lactate dehydro-
distribution width (PDW, %) and plateletcrit genase (LDH, U/l), aspartate aminotransferase

38 Journal of Tropical Pediatrics Vol. 56, No. 1


J. LIU ET AL.

TABLE 4
The changing in erythrocyte parameter in premature infants with and without PROM (x  s)

Groups n RBC Hb Hct MCV MCH MCHC RDW

Without PROM 50 3.95  0.42 149.8  17.3 0.49  0.09 110.3  6.07 37.3  1.69 336.8  18.6 16.9  1.91
With PROM 100 4.52  0.84 170.9  29.2 0.45  0.04 113.3  5.99 38.3  1.84 346.9  10.6 17.4  1.61
t 5.53 5.53 3.91 2.91 3.38 3.55 1.55
P 0.000 0.000 0.0001 0.0045 0.001 0.0007 0.12

TABLE 5
The changing in cardiac muscle enzyme in full-term infants with and without PROM (x  s)

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Groups n LDH AST CK CK-MB

Without PROM 50 536  217 52.6  35.1 428  238 59.9  45.8
With PROM 100 676  304 80.3  68.1 900  319 99.0  50.1
t 3.23 3.29 3.73 3.26
P 0.0016 0.0012 0.0003 0.0014

TABLE 6
The changing in cardiac muscle enzyme in premature infants with and without PROM (x  s)

Groups n LDH AST CK CK-MB

Without PROM 50 571  151 54.3  25.3 355  224 51.0  23.8
With PROM 100 660  303 68.3  41.7 605  316 89.8  47.7
t 2.40 2.55 4.12 4.58
P 0.018 0.012 0.0001 0.000

TABLE 7
The changing in blood levels of electrolyte in full-term infants with PROM (x  s)

Groups n Kþ Naþ Cl Ca2þ

Without PROM 50 4.54  0.57 138.3  3.90 101.9  4.59 1.96  0.33
With PROM 100 4.35  0.95 137.9  4.80 100.6  5.71 1.99  0.34
t 1.56 0.59 1.48 0.53
P 0.12 0.56 0.14 0.60

(AST, U/l), creatine kinase (CK, U/l), creatine in 100 premature infants and 100 full-term infants
phosphatase kinase-MB (CK-MB, U/l) were with PROM, and these parameters were compared
recorded in 100 premature infants and 100 full-term with those in 50 healthy premature infants and 50
infants with PROM, and these parameters were healthy full-term infants. The results are shown in
compared with those in 50 healthy premature infants Tables 7 and 8, respectively.
and 50 healthy full-term infants. The results are
shown in Tables 5 and 6, respectively.
Correlation between PROM and the incidence
of periventricular leukomalacia (PVL) in
Changes in blood electrolyte levels in infants premature infants
with PROM The incidence of PVL was 34.9% (355 of 1,017) in
Blood levels of electrolytes, including potassium (Kþ, premature infants with PROM and 24.9% (393 of
mmol/l), sodium (Naþ, mmol/l), chloride (CL, 1579) in non-PROM premature infants (2 ¼ 30.26,
mmol/l) and calcium (Ca2þ, mmol/l) were recorded P < 0.001).

Journal of Tropical Pediatrics Vol. 56, No. 1 39


J. LIU ET AL.

TABLE 8
The changing in blood levels of electrolyte in premature infants with PROM (x  s)

Groups n Kþ Naþ Cl Ca2þ

Without PROM 50 4.66  0.84 137.9  5.9 102.1  4.5 1.96  0.30
With PROM 100 4.93  0.84 136.7  4.7 103.5  6.1 1.94  0.33
t 1.81 1.88 1.67 0.42
P 0.073 0.062 0.098 0.68

Correlation between PROM and the incidence of Discussion


periventricular-intraventricular hemorrhage (PIVH)

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in premature infants The incidence of PROM in mainland China
The incidence of PIVH in premature infants was The results of the present investigation showed that
59.9% (610 of 1017) and 43.4% (693 of 1579) in the incidence of PROM in mainland China was
infants with and without PROM, respectively nearly 20%, which was similar to that found in
(2 ¼ 64.07, P < 0.001). Nigeria [12], but was much higher than that reported
in developed countries [4, 9]. There are almost
2 000 0000 pregnancies per year in China, thus
Influence of PROM on the duration of PROM complicates 4 000 000 annually. It has
hospitalization in neonates been suggested that PROM is more common in
The average durations of hospitalization in full-term mainland China and in other developing nations than
infants with and without PROM were 16.82  6.81 in more developed countries. It is therefore important
days and 14.02  4.73 days, respectively (t ¼ 3.85, to improve antenatal health care in order to reduce
P ¼ 0.0002), while the durations in premature infants the incidence of PROM, which can lead to fetal
with and without PROM were 24.4  14.8 days and death, stillbirth and other fetal and neonatal diseases.
19.5  7.50 days, respectively (t ¼ 4.41, P < 0.001).
The durations were prolonged by 20.0% in full-term Influence of PROM on fetal and neonatal health
infants with PROM and by 25.1% in premature PROM is associated with significant maternal, fetal
infants with PROM, compared with infants without and neonatal risks. A number of studies have
PROM. demonstrated that PROM may be strongly asso-
ciated with the subsequent development of adverse
neonatal outcomes such as neonatal death, PVL,
Influence of PROM on in-hospital costs PIVH, cerebral palsy and bronchopulmonary dys-
The average in-hospital costs for full-term infants plasia [1–15], especially among children of women
with and without PROM were 8913  5608 Yuan who develop chorioamnionitis after PROM [16].
RMB and 6832  3281 Yuan RMB, respectively Reports from Saudi Arabia showed that the inci-
(t ¼ 3.67, P ¼ 0.0003), while the costs for premature dence of neonatal mortality was 5.5%, respiratory
infants with and without PROM were 12 369  9339 distress was 15.9%, neonatal sepsis was 7.7% and
Yuan RMB and 7749  3467 Yuan RMB, respec- necrotizing enterocolitis was 3.1% in patients with
tively (t ¼ 8.18, P < 0.001). This represented an PROM [17], while results from France showed the
increase of 30.5% for full-term infants with incidences of neonatal mortality to be 11.7%,
PROM and of 60.0% for premature infants neonatal sepsis 15%, bronchopulmonary dysplasia
with PROM, compared with infants without 8.4% and cerebral injury 11.7% in cases with
PROM. PPROM between 24 and 34 weeks gestation [18].
Everest et al. [19] found that most liveborn infants
Influence of PROM on fetal death and stillbirth required neonatal intensive care, including mechan-
The incidences of fetal death and stillbirth were 2.7% ical ventilation (78%), if membrane rupture occurred
(786 of 29 143) in pregnancies with PROM and before 24 weeks’ gestation and had a latent period of
0.21% (252 of 120 057) in non-PROM pregnancies, 14 days’ duration. Airleak, occurred in 25% of
respectively (2 ¼ 2099.71, P < 0.001). survivors and in 67% of those who died. Among the
survivors, 43% required supplemental oxygen at 36
weeks’ postmenstrual age and 10 infants suffered
Influence of PROM on infant mortality from pulmonary hypoplasia. The results of this
Neonatal mortality was significantly higher in investigation show that PROM can result in several
PROM infants (220 of 1422, 15.47%) than in non- fetal and neonatal complications: (1) The incidences
PROM infants (38 of 5218, 7.28%) (2 ¼ 650.37, of fetal death, stillbirth and neonatal mortality were
P < 0.001). increased and were more common in twin

40 Journal of Tropical Pediatrics Vol. 56, No. 1


J. LIU ET AL.

pregnancies. This work found that the incidence of However, we found no effects of PROM on neonatal
fetal death and stillbirth was 2.7% and neonatal blood electrolytes.
mortality was 15.47%, which was lower than
previously reported. Kristensen et al. [20] reported Conclusion
that 6% of stillbirths, 15% of neonatal deaths and
Our study indicates that the incidence of PROM is
14% of infant deaths among twins in the United
higher in China than in developed countries. PROM
States were attributable to PROM. (2) The incidence
of premature birth was increased. The incidence of could affect numerous different aspects of the health
premature birth was 11.2% in our study. (3) There is of fetuses and neonates, including platelet para-
an increased risk of oligohydramnios, which can meters, erythrocyte parameters, neonatal jaundice
influence fetal development [21, 22]. The incidence of and myocardial injury. It therefore remains impor-
oligohydramnios was 12.8% in this group. (4) tant for Chinese doctors to improve the levels of
PROM can lead to fetal distress. The incidence rate antenatal, perinatal and postnatal health care in the

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of fetal distress was 15.1% in the present investiga- future.
tion. (5) The incidence of birth asphyxia was
increased. The incidence was 15.0% in this study.
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42 Journal of Tropical Pediatrics Vol. 56, No. 1

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