Volume 44, Issue 2 - Highlight: Current Topics on Ultrasound in Perinatology

Today we are living in a globalized world in which information on what is happening in one part of the world is easily communicated to other parts of the world. This happens thanks to advancement in science and technology. One area where technology has made the greatest impact is heath care provision. Ultrasound technology is now playing a critical role in health care provision particularly in Obstetrics and Gynaecology. This has significantly assisted in provision of quality health care to pregnant women and their unborn infants and in reducing maternal and neonatal morbidity and mortality in the developed world. Africa the continent with greatest health care challenges and with the highest maternal and neonatal mortalities is yet to fully utilize this important technology. The need for this technology is great as the conditions requiring its application abound. The effective application of Ultrasound however faces serious challenges in Africa. To successfully entrench Ultrasound in quality Obstetrics and Gynaecology care various approaches must be adopted to overcome the challenges. The aim of this paper is to identify the benefits and the challenges inimical to the application Ultrasound in Obstetrics and Gynecology in Africa. It also examines what needs to be done to achieve better application of Ultrasound in Obstetrics and Gynecology.

Gray-scale image data are processed in 3D ultrasound by repeated scans of multiple planes within a few seconds to achieve one surface rendering image and three perpendicular plane images. The 4D image is achieved by repeating 3D images in short intervals, i.e. 3D and 4D ultrasound are based on simple B-mode images. During 3D/4D acquisition, a fetus in utero is exposed by ultrasound beam for only a few seconds, and it is as short as real-time B-mode scanning. Therefore, simple 3D imaging is as safe as a simple B-mode scan. The 4D ultrasound is also as safe as a simple B-mode scan, but the ultrasound exposure should be shorter than 30 min. The thermal index (TI) and mechanical index (MI) should both be lower than 1.0, and the ultrasound study is regulated by the Doppler ultrasound if it is combined with simple 3D or 4D ultrasound. Recently, some articles have reported the functional changes of animal fetal brain neuronal cells and liver cell apoptosis with Doppler ultrasound. We discuss cell apoptosis by ultrasound in this report. Diagnostic ultrasound safety is achieved by controlling the output pulse and continuous ultrasound waves using thermal and mechanical indices, which should be <1.0 in abdominal and transvaginal scan, pulsed Doppler, as well as 3D and 4D ultrasound. The lowest spatial peak temporal average (SPTA) intensity of the ultrasound to suppress cultured cell growth is 240 mW/cm 2 , below which no ultrasound effect has been reported. An ultrasound user must be trained to recognize the ultrasound bioeffects; thermal and mechanical indices, and how to reduce these when they are higher than 1.0 on the monitor display; and guide the proper use of the ultrasound under the ALARA principle, because the user is responsible for ensuring ultrasound safety.

Mid trimester fetal anatomy scan is a fundamental part of routine antenatal care. Some U/S soft markers or controversial U/S signs are seen during the scan and create some confusion regarding their relation to fetal chromosomal abnormalities. Example of these signs: echogenic focus in the heart, echogenic bowel, renal pyelectasis, ventriculomegaly, polydactely, club foot, choroid plexus cyst, single umbilical artery. We are presenting an evidence based approach from the literature for management of these controversial U/S signs.

Trisomy 18 (T18) remains the second most common aneuploidy. It is associated with multiple congenital anomalies and causes intrauterine fetal demise in the most severe cases. Objectives: To examine the screening performance of ultrasound-based protocols for detecting T18, we aimed to determine the most common signs and their prevalence in fetuses with T18 to develop logistic regression model. Methods: This was a prospective study based on singleton pregnancies examined at gestation 11+0 to 13+6. The referrals constituted 6210 patients. Scan protocol enclosed a systematic review of the entire early fetal anatomy, including fetal cardiac evaluation and sonographic signs of aneuploidy. Results: Our study population comprised 5650 pregnancies: 5613 cases with a normal karyotype and 37 cases with T18. The mean nuchal translucency (NT) thickness in the subgroup of euploidy was 1.7 and in the subgroup of T18 it was 5.4. No statistically significant differences were found in terms of maternal age. One case of T18 (2.7%) demonstrated no markers of aneuploidy as opposed to 5111 cases of euploidy (91.1%). Extracardiac malformations were identified in 13 cases of T18 (35.1%) and in 48 cases of euploidy (0.8%). Congenital heart defects were observed in 26 cases of T18 (70.3%) and in 27 cases of euploidy (0.5%). Conclusions: Our results showed good screening performance of ultrasound-based risk calculation models. When the first trimester pattern of T18 is considered, an increased NT, tricuspid regurgitation, single umbilical artery, omphalocele and right dominant heart should be specifically searched for.

Objective: This paper describes the 20-year experience with selective feticide (SF) of high-order multiple quadruplet and higher pregnancies in a single center. Methods: The paper describes protocols, procedures, management, outcomes, and ethical issues. Results: SF was performed in 49 pregnancies with 244 fetuses, with median gestational age of 12+2 weeks. The initial number was nine (one case), eight (one case), seven (three cases), six (11 cases), five (eight cases), and four (27 cases). Nuchal translucency was utilized prior to the procedure starting in 1996. The technique was transabdominal ultrasound-guided and intrathoracic injection of potassium chloride. One pregnancy (with seven fetuses) was reduced to three, 42 to two, and four (starting with four fetuses) to singletons. There were ten pregnancy losses (20.4%). A decreasing trend in losses was evident over the 20-year time period: 7/23 (30.4%) from 1994 to 2004 down to 3/26 (11.5%) for 2004–2014. No chromosomal abnormalities were present in any of the survivors. The ethical issues focus on the justification of SF in high-order multifetal pregnancies. Conclusion: In this series, pregnancy loss decreased with operator experience. Excellent outcomes can be achieved with the ethically justified use of feticide in high-order multiple pregnancies.

Aim: To determine the accuracy of cervical elastography in predicting labor induction success. Materials and methods: A systematic search, review, and meta-analysis of observational studies published in English language between January 2000 and October 2014 was performed. It included studies considering cervix sonoelastography as the index test and successful labor or vaginal delivery as the reference standard. As cervix length and Bishop score were considered comparator tests, the quality of the included studies was assessed using quality assessment tool for diagnostic accuracy studies (QUADAS) tool. Results: A total of four studies assessing 323 women before medical induction of labor were included. Cervical elastography, cervical length, and Bishop score showed a diagnostic odds ratio (DOR) with 95% confidence interval (CI) for successful labor prediction of 3.50 (1.93–6.35), 3.35 (1.94–5.77), and 1.45 (0.33–6.41), respectively. In addition, cervical elastography, cervical length, and Bishop score showed a DOR with 95% CI for successful vaginal delivery prediction of 5.24 (3.23–8.50), 4.94 (2.72–8.98), and 4.62 (0.69–30.94), respectively. Considering the summary of receiver operating characteristic curves we show that cervical elastography or length are similarly reliable, and both are more reliable to predict successful labor than the Bishop score. Two studies were excluded because it was not possible to retrieve data for the meta-analysis. Among the excluded studies, one found no significant contribution from elastography for prediction of successful labor induction. Conclusions: Even though there is a limited number of studies included and the heterogeneity of the methods used, cervical elastography seems to be a promising tool for predicting successful labor induction and vaginal delivery in women treated by medical induction of labor.

Besides remarkable improvements of neonatal medical therapy, neurological morbidity remains a major concern in preterm infants. In particular, intracranial hemorrhage is a severe complication strongly correlated to poor neurological outcome. For early clinical assessment of intracranial hemorrhage and its impact on the ventricular system, cranial sonography is an important bedside diagnostic tool. Reference values of ventricular sizes are available in relation to gestational age (GA). So far, it has not been demonstrated that ventricular size values are also reliable in relation to birth weight (BW). In this study, we performed cranial ultrasonography in 250 preterm and term newborn infants. Measurements of the intracranial ventricular system by cranial ultrasound examination were performed within 72 h after birth. We determined ventricular index, anterior horn width, width of the third ventricle, width and length of the fourth ventricle for statistical analysis in relation to BW and GA. GA ranged from 23 weeks, 3 days to 42 weeks, 1 day (mean: 33 weeks), BW ranged from 345 to 5620 g (mean: 2146 g). Ventricular index and fourth ventricle width revealed a significant correlation to birth weight with r=0.75, each. A significant correlation to birth weight was also obtained for width and length of the third ventricle (r=0.55 and 0.47, respectively). Correlations obtained for ventricular measures in relation to GA were similar to those referring to BW. In preterm and term infants, ventricular sizes in relation to BW seem reliable for assessment and monitoring of ventricular pathologies, i.e. after intracranial hemorrhage.

Objectives: To investigate the possible effect of abnormal placentation disorders such as preeclampsia (PE), pregnancy induced hypertension (PIH) and intrauterine growth restriction (IUGR) on erythropoietin (EPO) serum concentration in women in the first trimester of pregnancy. Material and methods: A prospective study was performed in a group of pregnant women between 11 and 13 +6 weeks’ gestation. Serum concentration of EPO, beta HCG, PAPP-A and PlGF was measured. Mean arterial pressure (MAP) and uterine artery pulsatility index was calculated. Results: A group of 198 analyzed patients was divided into three groups depending on pregnancy outcome: abnormal placentation group (n=30), macrosomia (n=13) and control group (n=155). EPO concentrations between the three groups of patients revealed that they differ significantly (F=15.172, P<0.001). EPO concentration is significantly higher in abnormal placentation patients compared to the control group (P<0.001) and macrosomia group (P=0.004). The most significant increase in EPO concentration was detected within patients with PIH. Also the uterine artery pulsatility index was positively correlated with EPO concentration (P<0.01). Conclusions: First-trimester maternal EPO concentration might be considered as a possible marker of abnormal placentation disorders and should be given more attention in future prospective studies.

Aim: To determine the ultrasonographic findings that predict death in fetal ascites. Methods: This was a retrospective cohort study involving pregnancies with ultrasonographic findings related to fetal ascites. The inclusion criteria were as follows: single pregnancy with a live fetus; ultrasound findings of ascites; ascites unrelated to maternal fetal alloimmunization; and pregnancy follow-up at our institution. The χ 2 -test was used to evaluate the association of ultrasound findings and death. Multiple logistic regression analysis was performed to determine the ultrasound findings that are predictive of death prior to hospital discharge. Results: A total of 154 pregnancies were included in the study. In 8 (5.19%) cases, ascites was an isolated finding, and in 146 cases, other alterations were observed during the ultrasound evaluation. Death before hospital discharge occurred in 117 cases (76.00%). The following ultrasonographic findings were significantly associated with death: gestational age at diagnosis <24 weeks (P<0.0001); stable/progressive ascites evolution (P=0.004); the presence of hydrops (P<0.0001); and the presence of cystic hygroma (P<0.0001). The presence of hydrops, the presence of respiratory tract malformations, and stable/progressive ascites evolution were significantly associated with the prediction of death. Conclusions: Based on ultrasound examination, the presence of hydrops, malformation of the respiratory tract, and stable/progressive evolution of ascites increase the chances of death in cases of fetal ascites.

Background: Altered flow in ductus venosus (DV) may be caused by the changes in preload or afterload. Its association with aneuploidy and congenital heart defects (CHDs) was widely described. Objectives: The aim of this study was to examine the incidence of a reversed a-wave in DV flow (revDV) and the absence of DV (noDV), their coincidences with other markers of aneuploidy or fetal abnormalities in a mixed-risk population. Methods: The study group covered women who underwent an ultrasound scan between 11+0 and 13+6 weeks’ gestation. Applied inclusion criteria: Singleton pregnancies with known pregnancy outcome and a crown-rump length of 45–84 mm. Results: A total of 5811 cases, including 137 aneuploidies, met the inclusion criteria: 35 subjects of noDV, 189 of revDV and 5587 of normal DV flow. The incidence of noDV in euploidy was 0.47%, and in aneuploidy 5.8%. The incidence of revDV in euploidy was 2.46%, and in aneuploidy 35.7%. Among aneuploidy, the highest prevalence of noDV was found in monosomy 45X. revDV showed the highest prevalence in trisomy 18. Isolated noDV was only found in euploidy. Isolated revDV subjects were only observed in euploidy and trisomy 21. Any combination of revDV with additional markers showed high incidence in major trisomies. Extracardiac anatomy and abnormal cardiac findings showed a higher prevalence in noDV and revDV cases. Conclusions: The presence of noDV might be useful in suspicion of monosomy X among cases with increased nuchal translucency, as well as in differentiating them from other aneuploidies. The combinations of aneuploidy markers with revDV are strong indicators of aneuploidy. revDV alone is a poor screening tool for aneuploidy and euploidy with CHD.

Aim: To identify reference charts for femoral and humeral lengths enabling appropriate identification of fetuses <5 th percentile in one population. Methods: Two samples of fetuses aged 14–40 weeks were selected from our institution’s ultrasonographic database. Regression analysis was used to construct reference charts of femoral and humeral lengths based on the local population (n=901). Femur and humerus length measurements from a second sample (n=1240) were transformed into Z -scores using local and previously published equations. Z- score distributions were used to assess the appropriateness of reference curves for our population. Fetuses aged 18–24 weeks with measurements <5 th percentile were identified using each reference equation. Results: For femoral length, one equation other than the local equation yielded Z -score values within the standard normal distribution (P=0.10), but the histogram was skewed to the right. All Z -score distributions for humeral length fell within the normal distribution (P>0.05), but one was skewed to the right. The numbers of fetuses with femoral and humeral lengths <5 th percentile in second-trimester ultrasound examinations varied widely among reference equations used. Conclusion: Most reference charts assessed underestimated the number of fetuses with long bone lengths <5 th percentile in second-trimester ultrasound examinations and were thus unfit for interpretations of biometric data from the study population.

Aim: This study aimed to evaluate the ethnic difference in fetal behavior between Asian and Caucasian populations. Methods: Fetal behavior was assesed by Kurjak’s antenatal neurodevelopmental test (KANET) using four-dimensional (4D) ultrasound between 28 and 38 weeks of gestation. Eighty-nine Japanese (representative of Asians) and seventy-eight Croatian (representative of Caucasians) pregnant women were studied. The total value of KANET score and values of each parameter (eight parameters) were compared. Results: The total KANET score was normal in both populations, but there was a significant difference in total KANET scores between Japanese (median, 14; range, 10–16) and Croatian fetuses (median, 12; range, 10–15) (P<0.0001). When individual KANET parameters were compared, we found significant differences in four fetal movements (isolated head anteflexion, isolated eye blinking, facial alteration or mouth opening, and isolated leg movement). No significant differences were noted in the four other parameters (cranial suture and head circumference, isolated hand movement or hand to face movements, fingers movements, and gestalt of general movements). Conclusion: Our results suggest that ethnicity should be considered when evaluating fetal behavior, especially during assessment of fetal facial expressions. Although there was a difference in the total KANET score between Japanese and Croatian populations, all the scores in both groups were within normal range. Our results indicate that ethnical differences in fetal behaviour do not affect the total KANET score, but close follow-up should be continued in some borderline cases.

Aims: Sonographic estimation of fetal weight is a fundamental part of the routine obstetrical practice and may affect management decisions particularly in multiple gestations. The data available on the accuracy of sonographic estimation of fetal weight in triplets are very limited. In the present study we investigated the accuracy of sonographic fetal weight estimation and discordancy in triplet gestations. Methods: We analyzed the sonographic data of 33 sets of triplets born at one medical center between January 2001 and March 2013. Estimated fetal weight was calculated from biometric measurements and compared with actual neonatal weights following delivery. The Pearson correlation coefficient, linear regression analyses, and Bland-Altman method were used for statistical comparisons. Results: The differences between predicted and actual birth weights (ABW) were <10% in 69 newborns (70%), 10%–20% in 19 newborns (19%), and more than 20% in 11 newborns (11%). There was a good correlation between predicted and ABW (correlation coefficient=0.928, r 2 =0.86, P<0.0001). Conclusions: Weight assessment in triplets does not fall behind that of singletons or twins, and decisions based upon these examinations are reliable in the majority of cases.

Objective: To compare normal ranges of ultrasonographically measured fetal nasal bone length in the second trimester between different ethnic groups. Method: A prospective, non-interventional study in order to establish normal ranges of fetal nasal bone length in the second trimester in a Greek population was conducted in 1220 singleton fetuses between 18 completed weeks and 23 weeks and 6 days of gestation. A literature search followed in order to identify similar studies in different population groups. Fetal nasal bone length mean values and percentiles from different population groups were compared. Results: Analysis of measurements in the Greek population showed a linear association, i.e., increasing nasal bone length with increasing gestational age from 5.73 mm at 18 weeks to 7.63 mm at 23 weeks. Eleven studies establishing normal ranges of fetal nasal bone length in the second trimester were identified. Comparison of fetal nasal bone length mean values between the 12 population groups showed statistically significant differences (P<0.0001). Conclusion: Normal ranges of fetal nasal bone length in the second trimester vary significantly between different ethnic groups. Hence, distinct ethnic nomograms of fetal nasal bone length in the second trimester should be used in a given population rather than an international model.

Objective: To assess the prevalence of associated findings, diagnosed either prior to or after birth, among fetuses with increased nuchal translucency (NT) and normal karyotype and to investigate the prevalence of children under therapy at school age, among cases confirmed to be isolated both prior to and after birth. Methods: Retrospective cohort study of all singleton pregnancies were referred for the 1 st trimester screening for Down syndrome between January 2004 and December 2006. Cases with NT >95 th percentiles who undertook fetal karyotype were analyzed. We evaluated the prevalence of the following: (i) abnormal fetal karyotype, (ii) associated structural abnormalities, (iii) genetic syndromes, and (iv) children needing treatment (i.e. medications or psychopedagogical intervention) at school age. Results: There were 19 106 women screened for Down syndrome. Among them, 846 (4.4%) had a NT >95 th centile, of whom 541 (64.0%) undertook fetal karyotyping, 422 (78.0%) had normal karyotype, two (0.5%) opted for termination of pregnancy, and four (1.0%) ended in miscarriages. Among the 384 cases thought to be “normal” prior to birth, 14 (3.6%) were lost at follow-up and 10 (2.7%) had an associated abnormality diagnosed postnatally. Among the cases confirmed to be isolated, 10/270 (3.7%) were under treatment at the time of telephonic interview with parents. Conclusions: Parents should be informed that fetuses with increased NT and normal karyotype need detailed ultrasound scans during pregnancy and detailed pediatric evaluation at birth; if these are normal, the risk from adverse outcome at school age is the same as for general population.

Objectives: To examine the effect of antenatal betamethasone administration on Doppler parameters of fetal and uteroplacental circulation. Methods: Seventy-six singleton pregnancies that received betamethasone therapy were prospectively evaluated. Doppler measurements of pulsatility indices (PI) in fetal umbilical artery (UA), middle cerebral artery (MCA), ductus venosus and maternal uterine arteries were performed before (0 h) and 24, 48, 72 and 96 h after the first dose of betamethasone. Women with positive end-diastolic flow (EDF) in UA and those with absent or reversed EDF in UA were evaluated separately. Results: Fifty-two women with EDF in UA and 24 women with absent or reversed flow in UA were examined. Administration of maternal betamethasone was followed by a significant decrease in the PI of the MCA at 24 h (P<0.05). Additionally, return of absent to positive, reversed to absent or from reversed to positive diastolic flow in UA was detected within 24 h in 19 (79.2%) fetuses with absent or reversed UA-EDF. All alterations were transient and maintained up to 72 h. Conclusions: Antenatal administration of betamethasone is associated with significant but transient changes in the fetal blood flow. Hence, intensive surveillance of fetuses with Doppler ultrasonography is warranted following betamethasone therapy.

Objective: The objective of this meta-analysis is to assess the value of fetal cerebro-placental Doppler ratio (CPR) in predicting adverse perinatal outcome in pregnancies with fetal growth restriction (FGR). Methods: Three databases were used: MEDLINE, EMBASE (with online Ovid interface) and SCOPUS and studies from inception to April 2015 were included. Studies that reported perinatal outcomes of fetuses at risk of FGR or sonographically diagnosed FGR that were evaluated with CPR were considered eligible. Perinatal outcomes include cesarean section (CS) for fetal distress, APGAR scores at 5 min, neonatal complications and admission to neonatal intensive care unit (NICU). Pooled data were expressed as odds ratio (OR) and confidence intervals (CI), and the summary receiver operating characteristic (SROC) curve was used to illustrate the diagnostic accuracy of CPR. Results: Seven studies were eligible (1428 fetuses). Fetuses with abnormal CPR were at higher risk of CS for fetal distress (OR=4.49, 95% CI [1.63, 12.42]), lower APGAR scores (OR=4.01, 95% CI [2.65, 6.08]), admission to NICU (OR=9.65, 95% CI [3.02, 30.85]), and neonatal complications (OR=11.00, 95% [3.64, 15.37]) than fetuses who had normal CPR. These risks were higher among studies that included fetuses diagnosed with FGR than fetuses at risk of FGR. Abnormal CPR had higher diagnostic accuracy for adverse perinatal outcomes among “sonographically diagnosed FGR” studies than “at risk of FGR” studies. Conclusion: Abnormal CPR is associated with substantial risk of adverse perinatal outcomes. The test seems to be particularly useful for follow up of fetuses with sonographically diagnosed FGR.