DOI 10.1515/jpm-2013-0128      J. Perinat. Med. 2014; 42(3): 321–328

Arsenio Spinillo*, Barbara Gardella, Silvia Bariselli, Alessandro Alfei, Enrico Maria Silini and Barbara Dal Bello

Cerebroplacental Doppler ratio and placental histopathological features in pregnancies complicated by fetal growth restriction Abstract Objective: To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to the severity of the ratio of the pulsatility Doppler index (PI) of the fetal middle cerebral artery to that of the umbilical artery (cerebroplacental ratio, CPR). Study design: A cohort-study of 176 singleton pregnancies complicated by fetal growth restriction (FGR). Results: The mean values of gestational age, birth weight and CPR of the entire cohort were 33.9 ± 3.6 weeks, 1552 ± 561 g, and 1.33 ± 0.68, respectively. In ordered logistic regression analysis, after adjustment for potential confounders, muscularised arteries (Odds Ratio [OR] = 3.14; 95% confidence intervals [CI] = 1.58–6.28, P = 0.001), mural hypertrophy (OR = 2.35; 95% CI = 1.26–4.4, P = 0.008), immature intermediate trophoblast (OR = 2.0; 95% CI = 1.07–3.71, P = 0.03) and maternal vascular underperfusion (OR = 2.32; 95% CI = 1.25–4.23, P = 0.007) were the only parameters associated with severity of CPR. Conclusions: The correlation between placental histological findings indicating maternal underperfusion and placental occlusion suggest that forced centralization of fetal circulation in FGR could be at least partially attributable to the hemodynamic consequences of increased placental vascular resistance. Keywords: Cerebroplacental Doppler ratio; fetal brain sparing; fetal growth restriction; placenta histology preeclampsia. *Corresponding author: Arsenio Spinillo, Department of Obstetrics and Gynecology, University of Pavia, IRCCS Policlinico San Matteo, Viale Golgi, 19, Pavia, Italy, Tel.: +39 382 526215, Fax: +39 382 423233, E-mail: [email protected] Barbara Gardella, Silvia Bariselli and Alessandro Alfei: Departments of Obstetrics and Gynecology, University of Pavia. Fondazione IRCCS Policlinico San Matteo, Pavia, Italy Enrico Maria Silini: Unit of Surgical Pathology, Azienda OspedalieroUniversitaria di Parma, Parma, Italy Barbara Dal Bello: Department of Pathology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

Introduction Doppler velocimetry of fetal circulation is an effective tool in the clinical evaluation and management of pregnancies complicated by fetal growth restriction (FGR) [22]. Deterioration of Doppler velocimetry in the umbilical artery (UA) reflects progressive obliteration of placental tertiary villi with compromise of placental oxygen and nutritive exchanges [20, 26]. Increased placental resistance to blood flow causes significant modifications in fetal cardiac output [4]. In particular, increased resistance in the UA causes an increase in right fetal ventricular afterload and a shift of cardiac output towards the left ventricle to the fetal brain [2, 5]. In addition, the fetus adapts to placental insufficiency by vasodilation of cerebral arteries which can be detected as a decreased pulsatility index in the middle cerebral artery (MCA) [8]. The result of this blood flow redistribution is the so-called brain-sparing effect, a well-known adaptive change to preserve fetal brain oxygenation [8, 27]. The cerebroplacental ratio (CPR), a marker of the severity of the brainsparing effect, is a ratio of the pulsatility index of the MCA to the pulsatility of the UA, and measures the redistribution of fetal cardiac output taking into account both fetoplacental and cerebral vessels [5, 12]. Several studies suggest that CPR is a better predictor of adverse outcomes in FGR when compared to either UA or MCA pulsatility indices alone [13, 24]. Defective placentation is the leading cause of FGR, and in recent years a considerable effort has been made to standardize and quantify the individual placental histological findings associated with FGR [17–19]. Several studies have correlated pathological placental changes to worsening of the UA Doppler pulsatility index [20, 21, 23] in FGR and preeclamptic pregnancies. The purpose of this study was to evaluate the association of placental pathological lesions as defined by the Society for Pediatric Pathology [17, 18] to CPR in a cohort of pregnancies complicated by FGR.

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322      Spinillo et al., CPR and fetal growth restriction

Subjects and methods

2.

The series in the present study was composed of all pregnancies complicated by FGR diagnosed and followed-up at the high-risk pregnancy clinic of our department in 2008–2011. FGR was diagnosed when abdominal fetal circumference on ultrasonographic examination fell below the 10th percentile of our reference curve [25], confirmed on at least two consecutive measurements, two weeks apart, after the standard sonogram at 18–22 weeks. Subjects were enrolled after the diagnosis of FGR was made and eligibility criteria included, a) singleton pregnancy, b) a non-malformed and chromosomally normal fetus, c) enrolment for prenatal care at our Department during the first trimester of pregnancy, and d) scheduled antenatal surveillance and birth at our Department. The study was approved by the institutional review board of our hospital and patients gave their informed consent to participate in the study. Demographic data were collected at enrolment, whereas clinical data were collected during subsequent antenatal visits and at discharge from hospital. After first trimester enrolment, antenatal visits were scheduled at 18, 24, 30, 34, 38 and 40 weeks of pregnancy. After the initial sonogram obtained at 11–14 weeks of pregnancy, further ultrasonographic evaluations were scheduled at 18–22 and 28–32 weeks of pregnancy. When indicated, a conservative management plan of FGR was undertaken according to a defined protocol including antenatal visits, ultrasound surveillance, cardiotocographic monitoring, and administration of corticosteroids when a preterm birth earlier than 37 weeks was anticipated. The frequency of fetal surveillance was assessed at each visit according to maternal and fetal conditions. Ultrasound evaluation included weekly assessment of amniotic fluid volume and fortnightly fetal biometry. Doppler studies of fetal well-being included weekly or biweekly measurement of UA, MCA and ductus venosus blood flow velocity waveforms, depending on the initial severity of blood flow abnormalities. Weekly or biweekly computerized cardiotocographic fetal monitoring was scheduled according to the results of amniotic fluid volume measurement, Doppler studies and gestational age. The CPR was computed as a simple ratio of the MCA PI divided by the UA PI. To categorize the CPR values obtained, we used the percentiles derived by Ebbing et  al. [9]. The population under study was classified into three groups according to the following percentiles: CPR   10th percentile. Patients were admitted for close surveillance in the case of worsening of maternal or fetal conditions according to the judgment of the obstetric team of the high-risk pregnancy clinic (e.g., absent or reversed umbilical artery blood flow, severe preeclampsia). Preeclampsia was defined according to standard criteria [1]. Betamethasone (12 mg, two doses, 24  h apart) was administered to the mother if preterm birth at   10% of parenchyma and massive fibrin deposition or intervillous fibrin deposition involving more than 20% of the intervillous space; d) superficial implantation including acute atherosis and/or artery muscularization and/or placental site giant cells and immature intermediate trophoblast. Statistical analysis included χ2 analysis and Mann-Whitney U-test for categorical and continuous variables, respectively. Chi-square for trend and Spearman rank correlation coefficient were used to test for trends over proportions and continuous variables, respectively. Multivariable associations between categories (  10th percentile) of CPR severity (outcome variable) and histological variables were assessed by ordered logistic regression equations including gestational age, smoking (yes, no, former), and preeclampsia (yes, no) as confounders.

Results During the period of the study, out of 1934 women enrolled for antenatal care at our institution, 182 (9.4%) subjects had a diagnosis of FGR. Six women (3.3%) were excluded

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Spinillo et al., CPR and fetal growth restriction      323

from the study due to the unavailability of placental histological examination, leaving 176 cases for the final analysis. The main characteristics of the population under study are reported in Table 1. The prevalence of preeclampsia was 39.2% (69/176). The mean values of gestational age,

birth weight and CPR of the entire cohort were 33.9 ± 3.6 weeks, 1552 ± 561 g, and 1.33 ± 0.68, respectively. Test for trends showed that the rate of maternal smoking was inversely correlated with increasing severity of CPR, whereas rates of preeclampsia and cesarean section were

Table 1 Clinical variables and cerebroplacental Doppler ratio. Variables

   

Education (years)  5–8    9–12     > 12   Smoking  No    Yes    Quit in pregnancy   Parity  0    1      ≥  2   UA PI  Normal (EDV   90th pct)    Reversed or Absent    MCA PI   10th percentile    10–2.5 percentile      10 pct, (n = 56) N(%)



CPR   2.5 pct, (n = 33) N(%)



CPR  

Cerebroplacental Doppler ratio and placental histopathological features in pregnancies complicated by fetal growth restriction.

To correlate placental pathologic lesions, as defined by the Society for Pediatric Pathology, to the severity of the ratio of the pulsatility Doppler ...
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