8th Postgraduate Course for Training in Reproductive Medicine and Reproductive Biology

Preterm Premature Rupture of the Membranes

M. Gjoni
Albania

Tutor
J. Villar
HRP - UNDP/UNFPA/WHO/World Bank Special Programme

Introduction

Preterm premature rupture of the membranes (pPROM) is the classic case when a normal pregnancy becomes suddenly a high-risk one for mother and fetus/neonate. This complication has been and is still considered as one of the most serious events.

There are many studies dealing with this complication and yet there is no final general agreement on the assessment of fetal well-being, management and follow-up of the pregnancy up to the decision when to interrupt it.

During the last five years there seems to be enormous progress concerning the outcome of pregnancies complicated by pPROM.

Looking at the literature concerning pPROM there are different opinions revealed by several studies. Especially the smaller the gestational age of a pregnancy is, the bigger is the diversity of opinions of managing the problem.

Several authors advice obstetric services to build up their own protocol, based on the population’s specifications and socio-economic status as well as on the level of the health care offered by the hospital.

Definitions and abbreviations

Epidemiology

• demographic characteristics of the population studied;
• methods used for diagnosis;
• age of pregnancy at the moment of pPROM;
• type of study (retrospective or prospective);

In table 1, data from several studies between 1940 - late '80 are shown, including a large number of cases.

Table 1. Frequency of PROM

(from Anthony R. 12)

Table 2. Frequency of pPROM*

* In both studies more than 6.000 cases were surveyed.

Etiology

• the special anatomy of the membranes
• risk factors for their rupture
• protecting factors against pPROM

Few words on anatomy

The amnion is a mono-cellular epithelial layer, 0.02 - 0.05 mm thick and not vascularised. The connective tissue underneath contains dense filaments of collagen (25,47,62). Chorion is a 2 - 10 mm layer of cuboid cells, adherent to the decidua and perfused by dense vascularisation. This special structure makes the membranes more resistant to damage. If they are locally damaged by any factor which disappears later on, the membranes will probably restore their integrity.

Risk factors

• infection (cervico-vaginitis);
• cervical incompetence;
• smoking;
• invasive procedures in the cervix;
• low placental insertion;
• Ehlers Danlos syndrome;

In more than 50% of the cases, pPROM occurs during physical rest of the women. This fact indicates once the membranes are damaged, they loose their resistance and rupture spontaneousely. Infection is the major cause of membrane damage (5;26). The micro-organisms produce proteolytic enzymes and are often isolated in pregnancies complicated by pPROM. The use of antibiotics to prevent pre-term delivery has been successful in reducing the incidence of pPROM too.

The most frequent germs isolated in cases complicated by pPROM are: Chlamydia, Mycoplasma, group B Streptococcus (30; 31; 32). The same micro-organisms are often found to cause pre-term birth with intact membranes. In both cases, the level of immuno-globulins in the AL is high.

During normal pregnancy, collagen content of the membranes decreases gradually with increasing gestational age. It has been proven that in pregnancies complicated by pPROM, collagen content decreases earlier than in normal ones. This is one of the reasons that the membranes loose their mechanical resistance and rupture easily, even at rest.

The membranes are not damaged uniformly. The common place of rupture is the lower pocket because this is the locus where ascending infections attack.

Increased intrauterine pressure, especially acute, may be an adjuvant cause of pPROM (polihydramnion, multifetal pregnancy, etc.). On the other hand, this pressure reduces the utero-decidual perfusion of the membranes. Physical effort doesn’t seem to have any impact on preterm rupture (6, 27).

Protecting factors

A healthy vagina and a competent cervix are defined as good barriers to ascending infections. Cervical mucus plays also an important anti-bacterial role as well as the pH of a healthy vagina itself.

Diagnosis

There are no real prodroms of pPROM but amniorrhoea is in some cases preceded by lower pelvic pain (35%) and increased vaginal discharge (30%).

The leakage of amniotic fluid is the most common symptom of pPROM. In 1929, Phillip and Williams used to look through the microscope at samples from the posterior fornix, in order to distinguish lanugo. In 1942, Bourgeois coloured foetal fat cells, confirming the diagnosis of pPROM. In 1933, Temesvary found that the vaginal pH changes from 5 to 7 due to amniorrhoea. It was in 1944 when arborisation was used for the first time to diagnose pPROM with a low failure rate, a sensibility of 96-99% and specificity of 98-99%. The results may be misleading in the presence of blood, urine or meconium in the fornix (65).

A normal vaginal pH (3,5-4) is altered by the leakage of LA (pH = 7).

A very important tool for the diagnosis is ultrasound examination (66). Measuring the deepest pocket or calculating ALI, amniorrhoea can be diagnosed and the quantity of amniotic liquid can be followed throughout the pregnancy, thus confirming if oligo-amnios is still present or recovered. The presence of an anterior pocket is a valuable parameter of the pregnancy outcome. a -feto protein is also an important diagnostic marker f found in the posterior vagina.

Management

• pre-term delivery, surviving rates and long-term complications for the baby;
• infection risk for mother and fetus

Treatment

Several studies achieve better results by using antibiotic prophylaxis. Infection rates are closely related to the duration of latent period, vaginal examination or manipulation and to pre-existing cervico-vaginal infections. Microbiological examination of the vagina must be performed with the help of a speculum, measuring the pH and performing the arborisation test at the same time. The antibiogram will reveal the most efficient antibiotic which may be continued up to the end of pregnancy.

It is not suitable to use bacteriolytic antibiotics because of the toxins' induction of pre-term contractions. Fetal outcome is far better if prophylactic antibiotics are used (52).

On the other hand, some authors suggest to use antibiotics only when clinical signs appear and laboratory data confirm infection. They are concerned that antibiotic use would lead to microbial resistance in the neonate.

In 1972, Liggins used for the first time steroids to prevent the neonatal RDS, which is nowadays part of routine care for women in preterm labour. It is confirmed that the best results are achieved after the first treatment, beginning after 24 hours up to one week after. The second cycle of treatment gives a lower rate of RDS prevention. Intra-muscular rather than oral administration is suggested. Steroids appear to be successful to prevent RDS when administered in pregnancies between 27-30 weeks with prevention rates up to 50%. One has to keep in mind that steroids might increase the risk of infection (59).

It has been proven that steroid treatment is associated with a lower rate of long-term complications of pre-term born babies, matched for GA. Among babies receiving steroids in utero neurological impairment is less frequent compared to new-borns with higher birth weight.(2;33). Patricia C. refers to a follow up for a two to six year period (17).

The conclusions of the majority of studies reveal that in pregnancies complicated by pPROM the pulmonary maturation is accelerated compared to uncomplicated pre-term births of the same gestational age (41; 42; 56).

Table 3. Steroid effect on preventing RDS in pPROM pregnancies

• to give the possibility of using intra-muscular steroid treatment for 24 hours;
• to transfer the patient to a tertiary intensive care unit.

Assessment of fetal well-being

Up to ten years ago, amniocentesis was routinely performed as a routine for the detection of IAI. Recent studies have shown that amniocentesis at the time of recovery gives low diagnostic results (11; 15). Also, it is invasive and may be the cause of infection. Romero et al. in the early '90, have suggested that BPP has the same diagnostic accuracy as amniocentesis to detect IAI. In general, a score of 8 BPP is a good predictor for fetal well-being.

For example, normal foetal respiratory movements exclude IAI. For accurate assessment of fetal well-being, BPP should be performed once every 24 hours (43).

The assessment of AL quantity is also very important. If the greatest pocket is more than 2 cm, the risk of harm for the fetus is low. But for better accuracy, AFI should be calculated. If exposed for a long time to oligoamnios (9; 23), the fetus is at risk of developing non-renal agenesia (Potter syndrome). The duration of exposure may be as little as six days. (10; 29).

As the pregnancy progresses to term, NST is always more sensitive to assess fetal well-being. A reactive NST is associated with 93% fetal survival within one week.

• fetal lung maturation diagnosis;
• amnio-infusion;
• micro-biological investigation;
• local use of antibiotics;
• diagnostic confirmation by a dye;

Infection risk for the mother

There is a general agreement for the follow up of maternal infection. The classic screening implies: body temperature, which is regarded positive if more than 38° C for a duration of 24 hours or more, a heart rate of 100 or more / min, elevated WBC count, odorous vaginal secretion and uterine tenderness (48).

Table 4. Frequency of symptoms associated with IAI

If two or more of the above mentioned tests are positive, chorioaminionitis is considered to be present and interruption of pregnancy is advised. Several data confirm strong relationships regarding the time of first vaginal examination till delivery and maternal infection. Therefore, speculum use instead of a gloved hand is strongly advised when a vaginal approach is needed.

Evidence that IAI is caused by ascending germs was first shown by Knix and Hoerner in 1950. They proved that infection will attack membranes and make them susceptible to rupture. The first treatment goes back to 1966, when vagina was irrigated by non-specific antiseptics. The histopathology of the placenta, AL and membranes revealing the presence of germs were associated with pre-term birth at a rate of 23% (45; 48).

Decision for interruption of pregnancy

• Interruption of pregnancy is considered when the risk of infection overcomes the risk of prematurity. There are three major indications, which obviously suggest the interruption of pregnancy:
• fetal lung maturation;
• fetal distress;
• maternal and/or fetal infection;

The decision to interrupt the pregnancy varies from different countries and hospitals (18). It mostly depends on neonatal survival rates matched for gestational age as it appears in the following table:

Table 5. Neonatal survival rate of pregnancies complicated by pPROM

p.s. Surfactant has been used postnatally (Jonathan M, 14)

One also has to consider the specific situation for every pregnancy, e.g. age of the pregnant woman, obstetric history, other current risk factors, IUGR, diabetes, PIH, etc.

• 20-24 weeks of pregnancy: the survival rate is very low (less than 20-25%), with a very accurate expectant management of the pregnancy. Infection risk is very high and the long-term complications are very common and need an expensive follow-up. Therefore, termination of pregnancy is more often offered to the parents (60).
• 24-26 weeks of pregnancy: most of the studies suggest active management, checking for infection or fetal distress. In case of clinically apparent symptoms and positive laboratory results for chorio-amnionitis, it is advisable to interrupt the pregnancy by induction of labour (64). Caesarean section should be avoided if possible, being associated with a high rate of puerperal infection (39).
• 26-30 weeks of pregnancy: observation and follow-up are advisable. Antibiotic prophylaxis and steroids are considered to be of benefit. The risk of prematurity is higher than the risk of fetal/neonatal infection. This age-group has the highest benefits from the steroids treatment. Tocolysis is indicated if transfer to another health care unit is needed (58).
• 30-36 weeks of pregnancy: survival rate is high in this age-group (95%) (6). Lung maturation is achieved in more than 50% of cases, thus one has to check if steroids are needed. Antibiotics are advisable if the latent period is rather long. Interruption of pregnancy, once the diagnosis of IAI is confirmed, has no better outcome than using a antibiotics before induction is commenced. In this age-group induction failure rate is low and the need of C/S and its puerperal complications are rare (53; 55).

One has to keep in mind that if there is a lower pocket present, the risk of infection is low and expectant policy less risky. In about 10% of case amniotic leakage stops spontaneously and AL quantity is restored. It is suggested to admit the woman to the hospital and asses fetal well-being with daily US for a few days. If there are no abnormalities she may be discharged and re-examined after one week. Otherwise, discharging the patients from the hospital is not advisable.

Amnioinfusion is reserved for the cases where other indications for amniocentesis are also present. It is not advisable as a routine procedure and is useless if leakage continues.

Perinatal and neonatal outcomes are similar in twin and singleton pregnancies (54).

Repeated pPROM

Pre-term birth or pPROM in a previous pregnancy is associated with subsequent pPROM. If a positive history exists, the woman has to be assessed for the possible presence of risk factors (22), e.g. cervix incompetence, smoking. The two most frequent risk factors are: multifetal pregnancy and hydramnion. Infection and its inadequate treatment are the most common causes for repeated pPROM (22). A vaginal pH up to 4.5 or more, is associated with high risk for pPROM. Low genital tract cultures provide poor prediction of IAI and pPROM (50; 57).

References

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Edited by Aldo Campana,