METHODS
This prospective cohort study was conducted in the Department of
Obstetrics and Gynaecology in University College of Medical Sciences and
Guru Teg Bahadur Hospital, Dilshad Garden, New Delhi, India.
All women with a singleton pregnancy diagnosed with PPROM at gestational
age 28 + 0 to 33 + 6 weeks between November 2018 and April 2020 were
recruited. Gestational age was calculated using first day of last
menstrual and confirmed by ultrasonographic dating. Women who went in
spontaneous labor within 48 hours of PPROM or those with medical or
obstetric pregnancy complications, or with congenital malformation in
fetus were excluded from the study.
Diagnosis of PPROM was made by demonstrating vaginal pooling on sterile
speculum examination and/or the pH evaluation of fluid collected from
the posterior vaginal fornix. Following the diagnosis, expectant
management was instituted as per the institutional protocol. Tablet
erythromycin (250 mg) was given orally every 6 hour for 10 days.
Injection betamethasone was given 12mg, two dose, 24 hour apart for lung
maturity. Patient was kept on conservative management till completed 34
weeks or if she develop features of clinical chorioamnionitis or
abruptio placentae, or in case of non-reassuring fetal status. Patient
was observed for signs and symptoms of chorioamnionitis. Fetal
surveillance was done by daily fetal movement count, non stress test and
biophysical profile. Clinical chorioamnionitis was defined as presence
of fever ≥ 37.8° C along with two or more of following, i.e. maternal
leukocytosis (TLC > 15000 cells/mm3),
maternal tachycardia (heart rate > 100 beats/min), fetal
tachycardia (fetal heart rate > 160 beats/min), uterine
tenderness and foul smelling discharge.
All patients were subjected to ultrasonographic examination within 48
hours of admission. Various parameters such as presentation, placental
localization, amniotic fluid index, effective fetal weight were noted.
Fetal urine production rate was calculated by doing serial fetal bladder
volume measurements at an interval of 10 minutes. Bladder volume was
measured on E-cube 7, Alpinion Medical Systems, BPL using a 1.0-6.0 MHz
C1-6 convex array probe. Fetal bladder was first localized and focused
in two planes and measurements of anteroposterior diameter (i.e.
length), transverse diameter (i.e. width) and craniocaudal diameter
(i.e. height) were noted, and bladder volume was generated by formula
given by Campbell et al5 i.e.
Bladder volume =\(\frac{4}{3}\times\pi\times diameter\frac{a}{2}\times diameter\frac{b}{2}\times
diameter\frac{c}{2}\)Diameter a: anteroposterior diameter
Diameter b: transverse diameter
Diameter c: craniocaudal diameter
Bladder volume was measured 3 times ultrasonographically at an interval
of 10 minutes and fetal urine production rate (FUPR) was assessed by
change in fetal bladder volume over time. If the second value comes out
to be less than the first value as might occur with fetal voiding, then
the first value was discarded and the second value was taken as initial
measurement and two more values were estimated. Two values of FUPR were
calculated and the mean of the resulting two values was taken. The FUPR
was measured weekly till the patient delivered and the last measured
FUPR was used for analysis. The FUPR was compared with the gestational
age specific nomograms as given by Rabinowitz et al6.
FUPR was considered reduced if the value was less than the
5th percentile value of FUPR for that gestational age.
FUPR was considered normal if it falls between 5th and
95th percentile values for that age.
At the time of delivery, 2ml cord blood sample was taken in EDTA
container for measuring Interleukin-6 (IL-6) levels. The blood was
centrifuged and the separated plasma was stored at -80°C till estimation
of IL-6 levels (Diaclone IL-6 ELISA kit as per manufacturer’s
direction). The lower and upper detection limit for measurement of IL-6
levels were 1 and 200pg/ml. Some of our values of IL-6 levels were more
than 200 even after putting dilution. So, we had taken those values as
200 for the calculation of mean of IL-6 levels. Placental membrane and
cord tissue were collected and stored at room temperature in 10%
formalin and was sent for histopathological examination to look for
features suggestive of FIRS. Placental membrane was also sent for
bacteriological cultures. FIRS is defined by elevated IL-6 levels in
cord blood or presence of characteristic histologic features of placenta
which includes funisitis and chorionic vasculitis.
Neonates were assessed by pediatrician at birth and shifted to NICU as
per hospital protocol. Maternal outcomes were studied for delivery
outcome, postpartum complications. Neonates were followed up and
neonatal outcomes were noted as admission to NICU, duration of NICU stay
and neonatal morbidity. Severe neonatal morbidity was defined as
development of early onset neonatal sepsis (within 72hour), respiratory
distress syndrome, bronchopulmonary dysplasia, periventricular
leukomalacia, necrotizing enterocolitis or intraventricular hemorrhage.
All the procedures performed in this study on human participants were in
accordance with the ethical standards of the institutional research
committee (IEC-HR/2018/36/76R, dated 26/10/2018). Written Informed
consent was obtained from all the individual participants included in
the study. The study was funded solely by institutional funds –
Intramural grant from University College of Medical Sciences, New Delhi,
India.