Fetal Prenatal Diagnosis and Therapy

Abstract & Commentary

Synopsis: This study suggests that amnio infusion seems to be a low fetal and maternal risk technique that modifies the natural history of pPROM, improving fetal intrauterine stay and survival.

Source: De Santis M, et al. Fetal Diagn Ther. 2003; 18(6):412-417.

I review for and subscribe to a journal, Fetal Diagnosis & Therapy, that services predominantly subspecialists in prenatal diagnosis. For example, recently there were 3 wonderful papers on in utero stem cell transplantation. However, on occasion, there is a report that has general appeal to any provider dealing with pregnant patients, such as a recent paper by De Santis and colleagues from Rome.

The group was interested in studying the efficacy of amnioinfusion in early rupture of the membranes (pPROM). Seventy-one women with rupture of membranes at less than 26 weeks of gestation were "by chance" admitted to either of 2 hospital units between 1990 and 1999. With one exception, the management was the same for both sets of patients (ie, they all received antibiotics, tocolytics if contracting, and betamethasone). The only difference between the 2 regimens was that one team used the technique of amnio infusion in 37 patients with amniotic fluid indices (AFI) below 3 cm. The technique involved infusing enough sterile saline through an amniocentesis needle into the uterus to create an AFI of > 10 cm. The procedure was repeated weekly until delivery if the AFI, again, fell below 3 cm.

The length of time between pPROM and delivery was longer and the fetuses were delivered at an older gestational age in the "treated" group compared with controls (26 weeks vs 22.4 weeks). There also was a trend towards larger birth weight in the treated group (922 g vs 602 g). Last, the intrauterine survival rate was higher in the treated group (64.8% vs 32.3%). Interestingly, the diagnosis of amnionitis was lower in the amnio infusion group (16.2% vs 32.3%). Ultimately, there were only 10 neonatal survivals in the amnio infusion group (27%) and 6 in the control group (17.6%). In the 16 live-borns, 8 developed severe pulmonary hypoplasia and ultimately died (5 in the treated group and 3 in the control group). The characteristics of these 5 infants in the treated group were striking, when compared with the 19 "treated" live-borns without pulmonary hypoplasia. The hypoplastic infants had premature rupture of the membranes earlier (16 weeks vs 21.5 weeks), had double the latency period (79 days vs 43.9 days), and all 5 had substantial fluid loss within 6 hours of the amnio infusion vs 6 of 19 (31.6%) in those without pulmonary hypoplasia.

Comment by John C. Hobbins, MD

A black cloud descends on every patient rupturing membranes in the second trimester, and pessimists could find much to be gloomy about in this study, the ultimate ammunition being that only 10 of 34 treated infants eventually survived after an average of 4 amnio infusions per patient and an average of 41 maternal days in the hospital (at perhaps by US standards $1500 dollars per day). To be fair, however, the average time of rupture of membranes in both groups was 20 weeks and with a "glass half full" interpretation, a 26% early intact survival is not bad under these circumstances.

There are also some heartening nuggets to work with. For example, amnio infusion seemed to prolong the pregnancy and to substantially improve survival at birth and,  despite repeated entry into the uterine cavity, the rate of amnionitis was actually halved.

The Major Problems Associated with Very Early pPROM are:

1. Preterm birth;

2. Pulmonary hypoplasia;

3. Infection (intrauterine and neonatal).

Many studies have shown in pPROM that the smaller the residual quantity of amniotic fluid, the earlier the patient will deliver and the greater the chance of intrauterine infection. It would seem simplistic to postulate that lack of fluid per say was the root of pPROM-related problems. However, filling up the tank seemed to work not only in postponing delivery but also in diminishing amnionitis (without increasing neonatal sepsis).

So—amnio infusions or no, very early rupture of membranes is very hazardous to the health of fetuses, and patients who one way or another maintain their amniotic fluid volume seem to fare better by having longer latency periods and less intrauterine infections and will deliver fewer infants with pulmonary hyperplasia. Attempts to maintain amniotic fluid volume may help to circumvent some of the problems associated with early rupture of membranes but are of less help when the fluid leaks out immediately.

The second trimester is the period when fetal bronchiolar branching takes place, and, without adequate fluid traveling in and out of the lungs, this process will be impaired appreciably. Unfortunately, no amount of alveoli being laid down later in pregnancy or in the neonatal period will make up for this early deficiency. Then, unfortunately, it becomes "pay me now or pay me later."

A few reports have sprung up where attempts to close the membrane hole have had inconsistent results. Amnio infusion may be the answer in many of these patients, and in the next decade a plugging procedure might be best used in those who fail to maintain an adequate amniotic fluid volume after amnio infusion. Nevertheless, as in any potential perinatal problem, the less manipulation to accomplish an end, the better.