MATERIAL-METHOD
This prospective case control study was conducted in a tertiary
perinatal-neonatal center, between June 2020 and December 2020. The
study was approved by the Institutional Review Board of Ankara City
Hospital Ethics Committee. The research related to human use has been
complied with all the relevant national regulations, institutional
policies and in accordance the tenets of the Helsinki Declaration, and
has been approved by the authors’ institutional review board or
equivalent committee (E2-20-89). After verbal and written information
about the study, all eligible and voluntary participants gave informed
consent.
Eligibility criteria of participants included singleton pregnancies,
maternal age between 17 and 45 years, having no chronic systemic
diseases except IHCP. Exclusion criteria included multiple pregnancies,
preexisting maternal systemic disease (eg, diabetes mellitus, chronic
liver disease, hepatitis, chronic renal failure, rheumatological
disease), maternal hepatotoxic drug use. Additionally, fetal growth
restriction or macrosomia, known fetal structural malformation and/or
karyotype abnormality, and pregnancies complicated with preterm
delivery, premature preterm rupture of membranes, preeclampsia,
pregnancy-induced hypertension were excluded.
The gestational age was determined according to crown-lump length (CRL)
measurement between 11th and 14th gestational weeks. The medical records
of every eligible cases were reviewed the following variables were
recorded to dataset: maternal demographic characteristics (age, body
mass indices (kg/m2)), obstetric histories (gravidity, parity,
miscarriage, living child), pregnancy associated plasma protein A
(PAPP-A) MoM values that were obtained in the first trimester aneuploidy
screening, maternal liver function enzymes (aspartate aminotransferase
-AST (U/L), alanine aminotransferase - ALT (U/L)) and maternal serum
bile acid values that were reported at the time of diagnosis. The birth
characteristics (type of delivery, gestational age at birth, birth
weight, the APGAR scores 1. and 5. minutes), NICU admission and the
parameters of umbilical cord venous blood samples to determine acid-base
status of the newborns were recorded also. Neonatal acidemia at birth
was defined as either pH<7.2 or base deficit ≥12 mEq/L, in
agreement with the Neonatology Clinic.
All ultrasonographic measurements were performed using a Voluson E8
Expert ultrasound (GE Healthcare, USA), multifrequency convex transducer
at 3-9 mHz. After admission of participants for delivery, fetal
biometric measurements (biparietal diameter, head circumference,
abdominal circumference, femur lenght, thoracic circumference),
estimated fetal weight, fetal wellbeing, amniotic fluid index, Doppler
flow and velocity indices of umbilical artery, middle cerebral artery,
ductus venosus and fetal main pulmonary artery flow waveforms were
assessed by a single provider (BY).
A standardized measurement technique that was previously described by
Azpurua et al. 11, was used for fetal main pulmonary
artery flow waveforms. After obtaining four-chamber view of the fetal
heart, a slight probe rotation was performed to maintain the short axes
view that reveals the main pulmonary artery and its branches. The sample
volume gate was set between two and three millimeters and was placed
above the pulmonary valve. The angle of insonation was kept under 20
degrees. The time interval between the beginning of the ventriculary
systole and the first peak was defined as acceleration time (AT). The
time interval of ventricular systole was defined as ejection time (ET)
(Figure 1). These measurements were repeated three times and mean values
were recorded. The PATET ratio was obtained by dividing the acceleration
time to the ejection time (ET). By using the same flow-trace the main
pulmonary artery pulsatility and resistance indices were calculated.
Immediately after delivery, umbilical cord was clamped bilaterally and
umbilical venous blood samples from placental side were drawn into a
heparinized syringe. Umbilical venous blood pH, partial oxygen
(pO2) and carbon dioxide (pCO2)
saturation, bicarbonate, lactic acid, base excess (BE) were recorded.
Statistical analysis
The statistical analyses were conducted using the Statistical Package
for the Social Sciences (SPSS 22, IBM SPSS Statistics for Windows®,
Version 22.0 Armonk, NY:IBM Corp). The normality of distribution was
evaluated with histograms, probability plots and Kolmogrov Simirnov
test. The quantitative data were summarized as mean ± standard
deviation. Parametric comparisons were made by using theStudent T test. For all statistical analysis, p-value <0,05
with a 95%CI was considered significant. Correlation analysis was
conducted using Pearson analysis.