N-acetylcysteine in Intra-amniotic Infection/Inflammation

Despite extensive research, the etiology of most preterm births remains unknown. There are
significant fetal consequences associated with preterm birth, which include necrotizing
enterocolitis, fetal respiratory distress and intra-ventricular hemorrhage. Perinatal
mortality is about 44%, 11% and 5% when deliveries occur between 25-28 weeks, 29-32 weeks and
33-34 weeks, respectively. While for many years, it was assumed that the cause of the high
morbidity associated with prematurity was the birth of a neonate with a restricted adaptive
capacity, it has also been suggested that part of the high perinatal morbidity was the
consequence of adverse processes affecting the fetus in utero, rather than of prematurity per
se. Intra-amniotic inflammation present in utero early in gestation may trigger the cascade
of events leading to preterm birth (i.e. rupture of membranes, cervical ripening, uterine
contractions) and provide an intrauterine milieu which is unfavorable or even harmful to the
fetus.

Most living organisms have developed well-integrated, antioxidant defenses to scavenge free
radicals and control their intracellular concentration. A loss of balance between free
radicals and antioxidants (the redox balance) is one mechanism of cell injury in diseases
associated with inflammation. N-acetylcysteine is an approved anti-oxidant medication drug
used during pregnancy for treatment of mothers with acetaminophen (Tylenol) toxicity.
N-acetylcysteine has been safely administered during pregnancy in over 100 women who
overdosed with Tylenol and to preterm and healthy term newborns for other purposes. It is a
goal of our trial to prevent free radical formation by administering N-acetylcysteine and to
further study whether the outcome of preterm deliveries will improve compared to a control
group which will not receive placebo infusion

Inclusion Criteria:

- Women admitted onto the Labor and Birth Ward or Maternal Special Care Units of the
Yale New Haven Hospital who have a clinically indicated amniocentesis which
demonstrates presence of intra-amniotic infection and/or inflammation.

Exclusion Criteria:

- Patients that require immediate intervention or close medical supervision (cardiac and
renal disease, congestive heart failure, history of asthma), maternal infection (HIV,
hepatitis B or C), cord prolapse, known fetal malformation, allergic reactions to
N-acetylcysteine, preeclampsia