Athena P. Souka

Evaluation of a two-step ultrasound examination protocol for the detection of major fetal structural defects

Objective: To evaluate a two-step screening protocol of ultrasound examinations (11–14 and 20–24 weeks) for the detection of major fetal structural defects. Methods: Retrospective study in a private maternity hospital. Women with viable singleton pregnancies having both first trimester scan and anomaly scan at our department and subsequently delivered at our hospital were included. Major fetal structural defects were defined as those requiring medical or surgical treatment or those causing mental handicap. Results: A total of 3,902 pregnancies included 61 fetuses with structural defects (1.56%). Twenty-six (42.6%) were diagnosed in the first trimester and 29 (47.5%) in the second. Six anomalies were detected in the third trimester or after birth. Overall detection rate of the two-step program was 90.2%. Conclusions: Detailed examination of fetal anatomy at 11–14 weeks resulted in the early diagnosis of about 40% of major structural defects

Prediction of Preterm Delivery by Late Cervical Length Measurement after 24 Weeks

Objective: To examine the value of the cervical length (CL) measurement at 24-30 gestational weeks in the prediction of spontaneous preterm delivery (SPD) between 30 and 34 weeks (SPD₃₄) and between 34 and 37 weeks (SPD₃₇). Methods: We performed a prospective cross-sectional study. CL was measured once by transvaginal ultrasound examination between 24 and 30 weeks. Results: The study sample consisted of 1,180 low-risk singleton pregnancies. 10 women (0.85%) had a SPD₃₄ and 60 (5.08%) had a SPD₃₇. CL was shorter (p < 0.001) in the women who had a SPD₃₄ (median 11 mm) compared to the women who delivered after 34 weeks (median 31 mm). CL was shorter (p < 0.001) in the women who had a SPD₃₇ (median 22 mm) compared to the women who delivered after 37 weeks (median 31 mm). CL predicted SPD₃₄ (OR = 0.837, R² = 0.2768, AUC = 0.9406, p < 0.001) and SPD₃₇ (OR = 0.907, R² = 0.1085, AUC = 0.7584, p < 0.001). The model achieved a sensitivity of 70.0 and 38.3% for 10% false-positive rate for SPD₃₄ and SPD₃₇, respectively. Conclusions: CL after 24 weeks is significantly shorter in women destined to have a SPD. In low-risk singleton pregnancies CL performs very well in predicting SPD₃₄ and adequately in predicting SPD₃₇.

Cervical length at 11–40 weeks: unconditional and conditional longitudinal reference ranges

Our aim was to establish unconditional and conditional longitudinal reference ranges for cervical length throughout pregnancy.

Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan

Abstract Aim: To investigate the value of the birth weight of the previous pregnancy (BW1) alone and combined with the third trimester ultrasonographically estimated fetal weight (EFW) and Doppler studies in the prediction of small (SGA) and large for gestational age (LGA) neonates in the index pregnancy (BW2). Method: Some 1298 parous women with uncomplicated singleton pregnancies who had a third trimester ultrasound scan were considered as samples in this retrospective cohort study. Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle cerebral artery pulsatility indices were investigated as predictors of SGA and LGA. Results: BW1, maternal weight, mode of conception, and smoking status were associated with BW2 (R2=0.39) with BW1 being the strongest predictor (R2=0.37). The addition of EFW conferred significant improvement (R2=0.63), whereas the addition of the Doppler indices did not. The sensitivity of BW1 alone in the prediction of SGA was 75% for 25% screen positive rate and increased to 92% with the addition of EFW. The equivalent figures for LGA were 68% and 93%, respectively. Conclusions: BW1 used as a continuous variable is predictive of growth deviations in the index pregnancy. Incorporating EFW enhanced the sensitivity for the detection of both conditions.

Fetal volume at 11-14 gestational weeks: reference ranges and association with first trimester biochemical and biophysical markers.

Abstract Aims: To establish reference ranges for fetal volume (FV) measured by three-dimensional ultrasound (3D-US) at 11–14 weeks of gestation and to examine the possible association of FV with maternal/pregnancy characteristics and biochemical parameters. Methods: Prospective observational study on 240 fetuses at 11–14 weeks. FV was measured by 3D-US using Virtual Organ Computer-Aided Analysis. Pearson correlation coefficient (cc) and regression analysis were used. Results: FV increased exponentially with crown rump length and was unrelated to maternal weight (cc=–0.137, P=0.071), age (cc=0.009, P=0.899), parity (0.76), smoking status (t-test, P=0.149) and mode of conception (t-test, P=0.8). Z-scores (z) of FV was not associated with z-mean uterine artery pulsatility index (cc=–0.026, P=0.733), log10 multiples of the median (MoM) free beta human chorionic gonadotrophin (cc=0.002, P=0.982), delta value (d) of nuchal translucency (cc=0.072, P=0.331) and d-fetal heart rate (cc=0.009, P=0.902), z-FV was significantly positively correlated with log10 MoM pregnancy associated plasma protein-A (PAPP-A; regression coefficient=1.420976, R2=0.0957, P<0.0001). Conclusions: FV is strongly related to PAPP-A even after adjustment for crown rump length with a mechanism unrelated to placental perfusion. FV is independent of the vast majority of first trimester parameters; hence, it is a promising marker of early fetal growth.

First trimester fetal ultrasound parameters associated with PAPP-A and fβ-hCG

Objective: To study the association of fβ-hCG and PAPP-A measured at 11–14 weeks of gestation with delta crown-rump-length (dCRL), delta fetal heart rate (dFHR) and delta nuchal translucency (dNT). To calculate adjusted MoM taking into consideration these associations. Methods: Retrospective cross-sectional study on 5,536 singleton euploid pregnancies participating in a first trimester screening program for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry. Adjusted MoM were calculated for fβ-hCG and PAPP-A and compared to the observed MoM (calculated by the Fetal Medicine Foundation screening algorithm). Results: fβ-hCG correlates positively with dCRL and negatively with dNT, whereas PAPP-A shows a positive correlation with dNT and a negative one with dCRL and dFHR. After adjustment for the ultrasound parameters, the median MoM values for fβ-hCG and PAPP-A changed from 1.02 and 0.92 observed MoM to 0.98 and 0.99 adjusted MoM respectively. The difference between the observed and adjusted MoM was statistically significant (p < 0.001). Delta CRL increases with gestation and this effect manifests mainly after CRL of 62 mm. Conclusions: Adjustment for dCRL, dFHR and dNT improves the calculation of MoM for fβ-hCG and PAPP-A. CRL measurement overestimates fetal size at the end of the screening period 11–14 weeks.

First-trimester NRBC Count in Maternal Circulation: Correlation with Doppler Ultrasound Studies

This study aimed to determine whether the number of nucleated red blood cells (NRBCs) in maternal circulation during the first trimester of pregnancy could identify pregnancies that will have an anomalous Doppler in the second trimester. A total of 85 blood samples were obtained at 11–14 weeks of gestation with mean uterine arterial perfusion index >1.6, as noted by Doppler ultrasonography. NRBCs were enriched by magnetic automated cell sorting using anti-CD71 and were stained with May/Grunwald/Giemsa. A total of 4.8 NRBCs (range 1–75) were identified in 68 cases. Follow-up scans at 22–24 weeks were available in 46 cases. In 39 women, blood flow in the uterine arteries normalized, whereas in seven, high resistance was noted. One woman in the high-resistance group developed preeclampsia (PET; four NRBCs) and another delivered an intrauterine growth restriction (IUGR) baby (75 NRBCs). The number of NRBCs in women whose Doppler indices later normalized and in those who continued to have increased impedance was similar. The study indicates that NRBC number in maternal circulation during the first trimester cannot be used to screen pregnancies at high risk for developing preeclampsia (PET)/IUGR. High-impedance blood flow in the uterine arteries in the first trimester may be due to an unfinished process of trophoblastic invasion, most likely to be completed successfully by 22–24 weeks.

Quality assessment of the detailed anomaly ultrasound scan

Abstract Objectives: The objective of this study is to assess the quality of the views in the detailed anomaly ultrasound scan and examine the parameters that influence it. Methods: Prospective study on singleton pregnancies examined at 20–24 weeks. Detailed views of all fetal organs were classified by the examiner as optimal/suboptimal. The duration of the examination was observed. Maternal characteristics, Fat Index (FI) (distance between the skin and the surface of the uterus), and fetal position were recorded. Results: The study population consisted of 940 singleton pregnancies. Optimal visualization of all fetal structures was achieved in 66% of cases. Significant predictors were BMI, FI, and fetal position. None of the women with BMI ≥ 44 and none of the women with FI ≥ 60 mm had optimal visualization of all fetal structures. Median duration of the examination was 23 min. In 75% of cases, it was completed in the first attempt. Maternal weight, FI, and fetal position were the significant independent predictors of total examination time. Conclusions: Optimal visualization of the fetal anatomy is restricted by maternal parameters and fetal position. The main limitation is accumulation of abdominal fat, usually but not always related to maternal obesity. The FI may be recorded as a measure of technical difficulty. The anomaly scan should be allocated at least 30 min scanning time.

Second-Trimester Sonographic Diagnosis of Polymicrogyria.

A monochorionic diamniotic twin pregnancy was diagnosed at a gestational age of 12 weeks 3 days in a healthy 25-year-old nulliparous woman with unremarkable medical and family histories. The fetuses were of similar size; the nuchal translucencies were normal; the nasal bones were visible; there was no regurgitation in the tricuspid valves; and the flows in the ducti venosi were normal in both twins (crown-rump length, 54.2 mm; nuchal translucency, 1.3 mm for twin 1; and crown-rump length, 53.1 mm; nuchal translucency, 1 mm for twin 2). There was no difference in the amniotic fluid volume between the sacs. On follow-up visits, there were no signs of twin-twin transfusion syndrome at 16 and 19 weeks. At 19 weeks, twin 2 had borderline measurements of the posterior horns of the cerebral ventricles bilaterally (8.6 mm). At 21 weeks, the ventricular measurements of this twin became normal, but a hyperechoic area lateral to the exterior wall of both the cerebral ventricles was observed (Figure 1A). No structural defects were seen in either fetus, and the fetal biometric measurements, Doppler indices (umbilical artery, middle cerebral artery, and ductus venosus), and amniotic fluid volumes were normal in both. Initial fetal magnetic resonance imaging (MRI) at 22 weeks’ gestation showed normal brain development in twin 1 and abnormal development of the cerebral cortex with a similar appearance in both brain hemispheres in twin 2 (Figure 1B). There was extensive thinning of the periventricular white matter in the parieto-occipital brain lobes as well as thickening of the ventricular wall in the same areas. In addition, the sulcation of the frontal lobes appeared unusual for this gestational age, and the shape of the frontal horns of the lateral ventricles was abnormal. Maternal infection screening results were negative. The parents were counseled on the reserved prognosis, and they decided to continue the pregnancy. They subsequently were lost to follow-up until the 33rd week, when another sonographic examination showed normal amniotic fluid and fetal Doppler findings in both twins and no signs of twin-twin transfusion syndrome. The head circumferences were at the 10th and 5th percentiles for twins 1 and 2, respectively, and the estimated fetal weights were at the 5th and 8th percentiles. Careful examination of the brain of twin 2 did not show conclusive signs of abnormalities, and the ventricular measurements were normal (Figure 1C). Follow-up fetal MRI at 32 weeks’ gestation confirmed the initial concern regarding the cortex of twin 2 (Figure 1D). The imaging revealed pathologic evolution of the cortical development of both parieto-occipital lobes, which remained thinner than the other lobes and developed abnormal sulcation in the form of polymicrogyria. The imaging of the frontal lobes revealed unusual symmetric sulcation with the presence of deep sulci at the anatomic position of the superior frontal gyrus, as well as foci of heterotopias and focal polymicrogyria related to the site of abnormal sulcation. The parents opted for selective termination. The procedure was performed at 36 weeks, followed by immediate delivery of a healthy female neonate weighing 2100 g and a stillborn female fetus weighing 2000 g. A postmortem examination was declined. Polymicrogyria is a rare disorder of the cortical development characterized by multiple small abnormal infoldings of the cortex, which do not correspond to normal sulci. Fetal MRI shows heterogeneous imaging patterns, with perisylvian (61%), generalized (13%), frontal (5%), or parasagittal parieto-occipital (3%) localization.1 Known causes include congenital infections (particularly parvovirus B19 and cytomegalovirus) and localized or diffuse ischemia in utero. Emerging data highlight the importance of the genetic component in the pathogenesis of the disease.2 Polymicrogyria may also present in association with several chromosomal deletion and duplication syndromes, including the common 22q11.2 deletion (Di George syndrome).3 In most cases identified prenatally, the diagnosis was made by fetal MRI, which was performed because of a congenital infection or complications of monochorionicity (twin-twin transfusion syndrome or intrauterine death of one twin).4,5 Prenatal diagnosis of polymicrogyria based on sonographic findings has been reported in 4 cases.6–9 Malinger et al7 and Dhombres et al8 detected polymicrogyria associated with cytomegalovirus infection. The sonographic features were periventricular echogenicity, parenchymal calcifications, enlarged ventricles, and abnormal sulcation patterns. Delle Urban et al9 observed a hyperechoic area in the frontoparietal lobe of the donor twin of a twin-twin transfusion syndrome–complicated pregnancy at 25 weeks’ gestation. Both the location and the appearance of the lesion were very similar to those of the case we report. Our hypothesis is that this echogenic area corresponds to an accumulation of abnormal neurons that failed in the migrating process. Fetal MRI is paramount in the diagnosis of cortical and sulcal abnormalities as well as in excluding other coexisting brain abnormalities, such as corpus callosum agenesis/hypogenesis, cerebellar hypoplasia, periventricular nodular heterotopia, and subcortical heterotopia.1 Frontal sulcation becomes evident after the 25th week of gestation, and the MRI diagnosis can be established with certainty in Clinical Letters