Ceruloplasmin and Preterm Premature Rupture of the Membranes

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   Ceruloplasmin and Preterm Premature Rupture of the Membranes
Premature rupture of the membranes (PROM), defined as            ported in this issue are further confirmation of the hy-
rupture of the chorioamniotic membranes before the onset         pothesis that inflammation plays a role in PROM.
of labor, is a very common clinical problem in human                The association of active ceruloplasmin with term
pregnancy. In clinical obstetric terminology, PROM is            PROM is exciting and worthy of rapid confirmation by
defined as rupture of the membranes at term (within 3            other investigators. However, the real potential value for
weeks of the Estimated Date of Confinement, or due               these findings involves patients with preterm PROM. In
date). The reported incidence of PROM in term pregnancy          the developed world, the dominant contributor to perina-
is 8 –10%. Approximately one-fourth of PROM cases occur          tal morbidity and mortality in structurally normal babies
remote from term (i.e., at less than 37 completed gesta-         is premature birth. Despite aggressive tocolysis, the fre-
tional weeks) and are termed preterm PROM (often called          quency of preterm birth has not diminished over the past
PPROM).                                                          40 years (10 ). There is increasing evidence linking infec-
   Term pregnancies complicated by PROM are at in-               tion, both obvious and occult, with preterm birth (11 ). The
creased risk for several complications for mother and            biggest identifiable etiology of spontaneous premature
fetus. The likelihood of ascending maternal infection, or        birth is preterm premature rupture of the membranes,
chorioamnionitis, is directly related to the duration of         associated with 28 – 64% of all preterm births (12 ). There
membrane rupture, increasing from an overall rate of             currently is no method available that will accurately
0.5% to 3–15% with progressive duration of PROM (1 ).            predict subsequent preterm PROM.
The risk of neonatal sepsis (0.2% for all term newborns)            High fetal morbidity and mortality rates occur with
also increases both with the presence of PROM (1%) and           preterm PROM because of infection, premature labor,
with the duration of PROM (3–5% with PROM 24 h).                 fetal compromise from umbilical cord compression,
The dominant etiology for neonatal sepsis in contempo-           and/or fetal deformation (pulmonary hypoplasia and/or
rary American obstetric practice is the group B -hemo-           arthrogryposis) (13 ). Maternal complications are also
lytic streptococcus, and contemporary practice algorithms        more common with preterm PROM, with chorioamnioni-
amply document the association of PROM, particularly             tis rates as high as 25–35%. We now know that antibiotic
PROM of 18 h duration, as a risk factor for neonatal             treatment of women who experience this complication
sepsis requiring additional medical treatments for mother        will increase the interval to delivery and reduce maternal
and newborn (2 ).                                                and neonatal infection rates (14 ).
   Women of reproductive age now represent the most                 Late 20th Century American obstetric practice is
rapidly expanding population of AIDS patients, and it is         heavily invested in the notion of population screening.
now clear that untreated HIV-positive pregnant women             Readers of this journal are likely all familiar with algo-
have a 25–35% risk of transmitting the HIV virus to their        rithms for double, triple, and quadruple midtrimester
infant at the time of delivery (3 ). Vertical transmission can   serum screening, hepatitis B screening, glucose-tolerance
be minimized by appropriate antiretroviral prophylaxis,          screening, and Group B -hemolytic streptococcal screen-
scheduled cesarean section at 38 weeks (4 ), and by              ing among others. There is interest in some circles to
avoidance of certain recognized obstetric risk factors.          consider screening of the obstetric population with tests
These include invasive procedures, prematurity, chorio-          that may identify women at increased, or decreased, risk
amnionitis, and prolonged duration of ruptured mem-              of spontaneous preterm labor. These screening tests cur-
                                                                 rently include transvaginal ultrasound (15 ), fetal fibronec-
branes (particularly 4 h) (5 ). The ability to precisely
                                                                 tin measurements in cervicovaginal secretions (16 ), and
predict term PROM could be of value in these women
                                                                 salivary estriol (17 ). Unfortunately, all of these techniques
vis-a-vis timing of abdominal delivery.
                                                                 suffer from variably low sensitivity and specificity in
   The etiology of term PROM remains unclear and likely
                                                                 asymptomatic low-risk pregnant women and are not
involves a final common pathway for several related
                                                                 currently in widespread clinical use. The results reported
intrinsic and/or extrinsic processes. However, studies
                                                                 by Ogino et al. (9 ), IF equally applicable to preterm
comparing the tensile strength of membranes from pa-
                                                                 PROM, could improve our ability to identify that small
tients with term PROM to membranes from control pa-
                                                                 subset of the general obstetric population at risk for a
tients show no differences in tensile strengths except in
                                                                 devastating and costly complication of pregnancy. This
the membranes near the cervix, suggesting an ascending
                                                                 would then open the possibility of prophylactic strategies
etiology (6 ). Growing evidence also suggests that ascend-
                                                                 and/or randomized prevention trials.
ing, usually subclinical, infection and/or inflammation
plays an integral part in this process (7 ).
   Elsewhere in this issue, Ogino et al. (8 ) report an          References
association of active ceruloplasmin in cervicovaginal se-        1. Johnson JWC, Daikoku NH, Niebyl JR, Johnson TRB, Khouzami VA, Witter FR.
cretions of third-trimester pregnant women who subse-               Premature rupture of the membranes and prolonged latency. Obstet Gynecol
quently develop PROM. Ceruloplasmin is a known                   2. Prevention of perinatal group B streptococcal disease: a public health
plasma antioxidant that increases in concentration during           perspective. Morbid Mortal Wkly Rep 1996;45(RR-7):1–24.
inflammation (9 ), and it is likely that the findings re-        3. Conner EM, Sperling RS, Gelber R, Kiselev P, Scott G, O’Sullivan MJ, et al.

                                                                      Clinical Chemistry 45, No. 11, 1999                               1887
1888                                                                      Varner: Editorial

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