Prenatal diagnosis of Down syndrome: A 13-year retrospective study.

OBJECTIVE: The aim of this study is to summarize the experience on prenatal diagnosis of Down syndrome. MATERIALS AND METHODS: The study includes a retrospective data analysis of 157 prenatally detected cases of Down syndrome, routinely diagnosed among 6448 prenatal investigations performed during a 13-year period (2002-2014) in a single tertiary center. RESULTS: The prevalence of diagnosed Down syndrome cases was 2.4%. Maternal age alone was indication for prenatal diagnosis in 47 cases (45.2%), increased first-/second-trimester biochemical screening test in 34 cases (21.7%), abnormal ultrasound examination in 69 cases (43.9%), positive familial history for chromosomal abnormalities in four cases, and high risk for trisomy 21 revealed by cell-free DNA testing in three cases. Ultrasound anomalies were present in total of 94 fetuses (59.8%). The most common abnormality was cystic hygroma found in 46 cases (29.3%). A regular form of Down syndrome (trisomy 21) was found in 147 cases (93.6%), Robertsonian translocation in six cases (3.8%), and mosaic form in four cases (2.6%). CONCLUSION: In prenatal diagnosis of Down syndrome noninvasive screening methods are important for estimation of individual risks, in both, young population of woman and older mothers, while conventional and molecular cytogenetic methods are essential for definite diagnosis and proper genetic counseling.

Prenatal diagnosis of complex phenotype in a 13-week-old fetus with an interstitial multigene deletion 20q13.13.-q13.2 by chromosomal microarray.

We report the first trimester three-dimensional ultrasonographic findings in a 13-week-old fetus with complex phenotype and a de novo 4.7 Mb multigene deletion encompassing chromosome region 20q13.13-q13.2 detected by chromosomal microarray. Fetal sonography detected radial-ray anomalies in the form of bilateral absence of thumbs and the left club hand deformity. The presence of single atrioventricular canal instead of the atrial septal defect typical for Holt-Oram syndrome pointed us to rather suspect the SALL4 related diseases. Central nervous system anomaly in the form of enlarged lateral brain ventricles with choroid plexus shifted backwards was not previously reported as a part of SALL4 related disorders. The pregnancy was terminated at 14 + 3 weeks of pregnancy and the autopsy confirmed ultrasonographic findings. Deleted region included 38 genes, where only SALL4, ADNP and KCNB1 heterozygote pathogenic variants were described to be cause of syndromic forms. Radial ray anomalies are common part of clinical picture of SALL4 related disorders. Despite the lack of prenatally described cases, we hypothesized that maldevelopment of lateral brain ventriculomegaly could be very early sonographic sign of disturbed ADNP expression causing Helsmoortel-Van der Aa syndrome, but in some extent also of KCNB1 related early-onset epileptic encephalopathy. Furthermore, the possible dosage-dependent influence of recessive genes located in this region cannot be also excluded. The use of genome-wide technologies enables the detection of subtle chromosomal imbalances and more precise familial genetic counseling regarding actual and future pregnancies.

Prenatal diagnosis of 18p deletion and isochromosome 18q mosaicism in a fetus with a cystic hygroma.

Although, deletion of short arm of chromosome 18 is one of the most frequent autosomal terminal deletions, mosaic form of 18p deletion is infrequently observed. Furthermore, prenatally detected cases of 18p deletion and isochromosome 18q mosaicism are extremely rare. Herein, we present a case of del(18p)/i(18q) mosaicism, prenatally detected after chori- onic villus sampling. A 37-year-old woman was referred for prenatal diagnosis because of fetal septated cystic hygroma measuring 4.3 mm. Cytogenetic analysis showed a mosaic 46,XX,del(18)(p11.2)/46,XX,i(18)(q10) karyotype in both, short- and long-term culture. Parents elected to terminate the pregnancy. Fetal mosaic karyotype was confirmed by chromosomal analysis of cultured skin fibroblasts. Molecular characterization of chromosome 18 structural aberrations was performed by fluorescence in situ hybridization (FISH). Considering variable ultrasound findings among cases with del(18p)/i(18q) mosaicism, we emphasized that first and second trimester ultrasound screening examinations for fetal malformations, followed by cytogenetic and molecular evaluations, are very important in the management of prenatally detected cases.

Allergic reaction to suxamethonium during emergency caesarean section and pseudocholinesterase deficiency in the same patient.

An allergic reaction during the caesarean section can be harmful for mother and foetus. Our patient has undergone an urgent caesarean section due to the imminent threat of foetal hypoxia. After operation, we applied prolonged mechanical ventilation. The anaesthesia was induced with thiopental and suxamethonium. Suxamethonium is associated with the highest incidence of allergic reactions but it is a neuromuscular blocking agent of choice for an emergency operation. During the operation, about 10 min. after induction, the systolic blood pressure dropped suddenly to 67 mmHg, the heart rate increased to 145 beats per minute and the oxygen saturation dropped to 60 %. A small degree of bronchospasm developed but there wasn't any kind of skin reaction. We thought of an allergic reaction, the obstetrical pulmonary embolism and an acute cardiac failure. The baby was delivered promptly in good condition. Within 10 min. all vital signs normalized. The operation continued without problems. Unexpectedly, during waking up from anaesthesia the patient became dyspnoeic, laryngospasm appeared, the oxygen saturation dropped again, strong facial and tongue oedema appeared and an urgent reintubation had to be performed. The laboratory results pointed out elevated mast cell tryptase level and significant pseudocholinesterase deficiency. About 2 months later, immunologist excluded thiopental and latex, and suggested that suxamethonium was the "trigger" factor. In our case the respiratory insufficiency was caused by two different and unrelated pathological mechanisms: biphasic allergic reaction and prolonged neuromuscular block caused by pseudocholinesterase deficiency.

Prenatal diagnosis of sex chromosome aneuploidies and disorders of sex development--a retrospective analysis of 11-year data.

OBJECTIVE: Analysis of prenatally diagnosed sex chromosome aneuploidies and disorders of sex development (DSDs). METHODS: This study includes a retrospective data analysis of 46 prenatally detected sex chromosome aneuploidies and one case of 46,XY DSD diagnosed during an 11-year period (2002-2012) at our department. RESULTS: Of the 46 sex chromosome aneuploidies, 29 cases (63.0%) were in the group of a selected population of women according to abnormal first-/second-trimester ultrasound and 17 (37.0%) cases in an unselected population of women who underwent fetal karyotyping because of advanced maternal age. The most common aneuploidy was Turner syndrome in full and mosaic form (50%). Complete androgen insensitivity syndrome was diagnosed in the case of 46,XY DSD. CONCLUSIONS: Sex chromosome aneuploidies must be taken into consideration if, in the first or second trimester, abnormalities are revealed on ultrasound, mainly Turner syndrome in full or mosaic form and 47,XYY.

Modification of conservative treatment of heterotopic cervical pregnancy by Foley catheter balloon fixation with cerclage sutures at the level of the external cervical os: a case report.

INTRODUCTION: Conservative treatment of a heterotopic cervical pregnancy was performed with a modification of the fixation of a Foley catheter at the level of the external cervical os, followed by the ligature of the descending cervical branches of the uterine arteries and systemic methotrexate application. CASE PRESENTATION: A 34-year-old Caucasian woman was diagnosed with double gestation after 6 weeks of in vitro fertilization treatment. A gynecological examination and color Doppler ultrasound scan revealed intra-uterine and cervical gestational sacs both containing live fetuses. A Foley catheter balloon was inserted into the cervical canal, inflated and fixed by a cerclage suture at the level of the external cervical os, followed by ligation of the descending cervical branches of the uterine arteries. Systemic methotrexate was applied. Three days after removal of the Foley catheter, an evacuation of the intra-uterine gestational sac was performed. Hemorrhage from the implantation site was controlled immediately and a pregnancy termination was successfully performed. The procedure was uneventful and our patient was discharged with a preserved uterus. CONCLUSIONS: Conservative treatment of cervical pregnancy using a Foley catheter balloon is more efficacious if the Foley catheter balloon is attached in the correct position with a cerclage suture at the level of the external os, followed by ligation of the descending cervical branches of the uterine arteries, thereby exerting maximal pressure on the bleeding vessels.

Normal standards for fetal neurobehavioral developments--longitudinal quantification by four-dimensional sonography.

AIM: To construct normal standards for fetal neurobehavioral development using longitudinal observations through all trimesters by four-dimensional sonography. SUBJECT AND METHODS: A group of 100 healthy normal singleton pregnancies were recruited for longitudinal 4D US examinations to evaluate fetal neurodevelopmental parameters between 7 to 40 weeks' gestation. Variables of maternal and fetal characteristics including gestational age, eight fetal movements patterns in the first trimester and 14 parameters of fetal movement and fetal facial expression patterns recorded thereafter for the construction of fetal neurological charts. RESULTS: Measurement of 7 parameters in the first trimester and 11 parameters in the second and third trimesters correlated with gestational age (P<0.05). Those parameters have been followed longitudinally through all trimesters and showed increasing frequency of fetal movements during the first trimester. A tendency towards decreased frequency of facial expressions and movement patterns with increasing gestational age from second to third trimesters has been noticed. CONCLUSION: With 4D sonography, it is possible to quantitatively assess normal neurobehavioral development. There is urgent need for further multicentric studies until a sufficient degree of normative data is available and the predictive validity of the specific relationship between fetal neurobehavior and child developmental outcome is better established.

Knowledge and use of folic acid in Croatian pregnant women--a need for health care education initiative.

Adequate periconceptional folic acid (FA) intake reduces the risk of neural tube defects. There are still no official FA supplementation guidelines, FA fortification policies or larger studies of awareness regarding FA or number of planned pregnancies in Croatia. This study assesses the knowledge and practice regarding FA supplementation and reports the trends in pregnancy planning in Croatia. A total of 569 pregnant women completed an anonymous questionnaire and about 72% of them were aware of the benefits of FA. Despite 75.53% of planned pregnancies, only 14.41% of all women took FA appropriately. Croatian women get information about FA from the media, health professionals and friends, but 63.77% got this information too late. The present study showed low percentage of appropriate FA intake despite high number of planned pregnancies in Croatia. It emphasizes the need for immediate and continuous public health education initiative about FA intake targeted to the women of childbearing age before their pregnancies have occurred.

The Misgav Ladach method--a step forward in operative technique in obstetrics.

AIM: To investigate the advantage of performing cesarean section using the Misgav-Ladach method and to justify its use in everyday practice. METHODS: In a prospective study we analyzed over a two year period (2000-01) cesarean sections carried out using the Misgav-Ladach method at our clinic. We compared both 550 cases of Misgav-Ladach (ML) and 100 cases of Pfannenstiel (PH) cesarean section. In the group that had undergone the Misgav-Ladach method we sutured the uterus in one layer and left the peritoneum non-sutured, and in the group who had undergone Pfennenstiel we sutured the uterus in two layers and also sutured the visceral and parietal peritoneum. In every case we analyzed: maternal age, gestational age, duration of operation, consumption of suture material, duration of hospitalization, and surgical complications. RESULTS: Incidence of postoperative febrile morbidity was 5.45%, in the Misgav-Ladach group compared with 13.2% in the Pfannenstiel group (p < 0.05). Local infection of the wound in the Misgav-Ladach group was found in 4.54% and in the Pfannenstiel group in 9% (p < 0.05). Mean time of extraction of the newborn in the Misgav-Ladach group was 1.25 minutes, and in the Pfannenstiel group 4.10 minutes (P < 0.05). Mean duration of operation in the Misgav-Ladach group was 10.98 min, and in the Pfannenstiel group 25 min (p < 0.05). Mean duration of hospitalization in the Misgav-Ladach group was 4.75 days, and in the Pfannenstiel group 6.32 days (p > 0.05). Mean consumption of suture material in the group Misgav-Ladach was 3.10 sutures per operation, and in the Pfannenstiel group was 9.5 sutures. CONCLUSION: Our study shows that the Misgav-Ladach method of cesarean section enables fast recovery and shorter hospitalization, and reduces the length of the operation, the incidence of surgical complication and the consumption of surgical materials.

Three-dimensional power Doppler in study of embryonic vasculogenesis.

Three-dimensional power Doppler sonography plays an important role in obstetrics, predominantly for assessing the relationship between fetal vascular system and surrounding organs. Presenting volume data in a standard anatomic orientation is valuable for assisting both ultrasonographers and pregnant patients to recognize anatomy more readily. This investigation was designed as an observational cross-sectional study. A group of 25 patients in gestational age of five to eleven weeks were recruited for the study. Architecture of the embryonic vessels was depicted by 3D power flow mapping and analyzed visually. Vascular 3D measurements were done through 3D color/power histogram and expressed by Vascularization Index (VI) and Vascularization Flow Index (VFI). Volume of the embryo increased exponentially throughout the observation period. The VI and VFI showed no change despite an exponential growth of embryonic volume. The findings of our study suggest that in cases of physiologic embryonic vasculogenesis there is a homeostatic steady state between tissue demands and blood supply given through the vascular network.

Assessment of early chorionic circulation by three-dimensional power Doppler.

Three-dimensional power Doppler sonography is a unique instrument that enables assessment of vascular signals within the whole investigated area. Hemodynamical changes included in the process of early placentation are one of the most exciting topics in investigation of early human development. This investigation was designed as an observational cross-sectional study. A group of 25 patients in gestational age five to eleven weeks were recruited for the study. After acquirement of the volume containing three-dimensional power Doppler data of the pregnant uterus, the signals belonging to the chorion were isolated. Vascular 3D measurements were undertaken through 3D color/power histogram and expressed by Vascularization Index (VI) and Vascularization Flow Index (VFI). Volume of the chorion increased exponentially throughout the observation period. The VI and VFI positively correlated with the crown-rump length and chorion volume, and showed gradual increment through the investigation period. This investigation produced results confirming gradual augmentation of the loci and intensity of the intervillous flow in pregnancies between five and eleven gestational weeks.

Limb deformities and three-dimensional ultrasound.

AIM: To assess the ability of three-dimensional (3D) ultrasonography for improvement of antenatal detection of limb deformities. METHODS: 347 patients were selected from a routine outpatient clinic or sent for supervision from other units because of suspected anomalies of fetal extremities. 3D ultrasound devices used in the study were Combison 530D and Voluson 530D MT (Kretztechnik, Zipf, Austria) with a 3-5 MHz annular array transducer for three-dimensional volume scanning. RESULTS: In 41 of 347 patients the initial diagnosis was suspected by two-dimensional sonography (gestational age 18-32 weeks). In 28 of 41 suspected cases the diagnosis of abnormalities was determined after examination by 3D sonography: 17/28 clubfoot, 3/28 hand-polydactily, 2/28 upper limb contractures, 1/28 lower limb contractures, 4/28 micromelia within the syndrome of skeletal dysplasia. In 13 of 41 suspected cases, normal anatomy was confirmed using 3D sonography. CONCLUSION: Three-dimensional sonography is the "method of choice" for the detection of an isolated defect of a single limb, developmental or positional deformations and minor defects of hands and feet. Surface-mode reconstruction of the complete limb and transparent-view reconstruction of the entire skeletal structure are effective technical advantages enabling a completely new visual perception of the unborn baby.

Prenatal diagnosis: what does four-dimensional ultrasound add?

INTRODUCTION: The key benefit of 4D ultrasound lies in providing real-time 3D images of embryonic or fetal movements, previously limited by technological advancement. AIM: To classify types of first trimester embryonic and fetal movements in normal pregnancies as seen by 4D sonography. RESULTS: Three types of movements can be visualized in the first trimester: gross body between seven and eight weeks, limb movements after ten weeks and complex limb movements after 11 weeks of gestation. DISCUSSION: An alteration from the given pattern of motoric development should be considered as an indication for further investigation. CONCLUSION: 4D ultrasound enables visualization of more details of the dynamics of small anatomical structures. Therefore, body and limb movements can be visualized a week earlier than with 2D.

Three-dimensional sonoembryology.

Three-dimensional (3D) ultrasound plays an important role in obstetrics, predominantly for assessing fetal anatomy. Presenting volume data in a standard anatomic orientation valuably assists both ultrasonographers and pregnant patients to recognize the anatomy more readily. Three-dimensional ultrasound is advantageous in studying normal embryonic and/or fetal development, as well as providing information for families at risk for specific congenital anomalies by confirming normality. This method offers advantages in assessing the embryo in the first trimester due to its ability to obtain multiplanar images through endovaginal volume acquisition. Rotation allows the systematic review of anatomic structures and early detection of fetal anomalies. Three-dimensional ultrasound imaging in vivo compliments pathologic and histologic evaluation of the developing embryo, giving rise to a new term: 3D sonoembryology. Rapid technological development will allow real-time 3D ultrasound to provide improved and expanded patient care on the one side, and increased knowledge of developmental anatomy on the other.

Three-dimensional (3D) ultrasound--a useful imaging technique in the assessment of neonatal brain.

Clinical application of ultrasound began about fifty years ago. From one-dimensional A-mode, through two-dimensional real time and Doppler examinations, a new era in clinical ultrasonography then began in the late eighties. Development of computer technology enabled introduction of 3D ultrasonography into clinical practice. In obstetrics ultrasound revolutionized fetal follow-up, but it was as important for the detection of intracranial pathology during the neonatal period and infancy. Two-dimensional real time ultrasonography was [table: see text] an exciting method that changed our understanding of the prevalence and pathophysiology of brain pathology in premature and term infants. Will application of 3D ultrasonography bring any substantial improvement to neuroimaging diagnostics in the newborn period? This article attempts to find the answer to this question, despite the limitations set by the short period of application of 3D neurosonography in neonates. The advantages of 3D brain ultrasonography application in neonates are: quicker and observer independent data acquisition, the possibility of off-line data analysis, projection of 3D data on a 2D plane with volumetric, color and power Doppler studies. Unavailability of equipment is the main reason why 3D ultrasonography was performed in only half of the newborns in whom it was indicated. Cost of equipment prevents introduction of 3D as a standard diagnostic procedure in neonates, although its diagnostic value is indisputable.

Events from ovulation to implantation studied by three-dimensional ultrasound.

During the last decade transvaginal color Doppler has played an important role in increasing understanding of early human development. Although our knowledge of early pregnancy development has recently improved, little is known about the most critical period of human development: between conception and implantation. Recent advances in 3D ultrasound have made studies of follicular development, ovulation and uterine receptivity more accurate. The same method can be used for evaluation of the Fallopian tube patency and assessment of the ovarian and uterine causes of infertility which hamper processes of early human development. Storage capacities, reconstruction of the volume images and simultaneous viewing of all three orthogonal planes are the main advantages of this method. Introducing 3D ultrasound into assessment of early pregnancy has enabled visualization and volume estimation of the gestational sac, yolk sac and embryo. Switching on power Doppler superimposed to 3D gray scale can detect early vasculogenesis within the intervillous space and embryo/fetus. Here we review the potential application of this novel technique in monitoring the morphological and functional processes from ovulation towards implantation and early pregnancy.