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.