Savitree Pranpanus

Reliability of fetal nasal bone length measurement at 11–14 weeks of gestation

BackgroundNasal bone assessment has been incorporated into Down syndrome screening in first trimester. Several studies have established the normal reference values for fetal nasal bone length in the first trimester, which were found to be varied by population. However, the study on reliability of nasal bone length measurement was limited with contradictory results. This study aimed to investigate the reliability of fetal nasal bone length measurement at 11–14 weeks of gestation in the Thai population.MethodsA total of 111 pregnant women at 11–14 weeks of gestation attending for the routine first-trimester ultrasound examination were recruited. Each case was measured separately by two examiners. Examiner 1 performed the first measurement in all cases; any of the other 5 examiners consecutively performed the second measurement. Three independent measurements were performed by each examiner and they were blinded to the results of the others. Intraobserver and interobserver variabilities were evaluated with the intraclass correlation coefficient (ICC).ResultsNasal bone measurement was successfully performed in 106/111 cases (95.5%) by at least one examiner; 89 cases were performed by two examiners. The intraobserver variability was excellent for all examiners (ICC, 0.840-0.939). The interobserver variability between different pairs of examiners varied from moderate to excellent (ICC, 0.467-0.962). The interobserver variability between examiner 1 and any other examiner was good (ICC, 0.749). The Bland-Altman plot of the interobserver differences of nasal bone length measurements between examiner 1 and any other examiner showed good agreement.ConclusionsThe reliability of the fetal nasal bone length measurement at 11–14 weeks of gestation was good. The nasal bone length measurement was reproducible. Ethnicity has an effect on fetal nasal bone length, but reliability of nasal bone length measurement is critical to accuracy of screening and should be audited on an ongoing basis.

Effectiveness of the model for prenatal control of severe thalassemia

The aim of the research was to determine effectiveness of the model for prenatal control in reducing new cases of severe thalassemia.

A growing animal model for neonatal repair of large diaphragmatic defects to evaluate patch function and outcome

Objectives We aimed to develop a more representative model for neonatal congenital diaphragmatic hernia repair in a large animal model, by creating a large defect in a fast-growing pup, using functional pulmonary and diaphragmatic read outs. Background Grafts are increasingly used to repair congenital diaphragmatic hernia with the risk of local complications. Growing animal models have been used to test novel materials. Methods 6-week-old rabbits underwent fiberoptic intubation, left subcostal laparotomy and hemi-diaphragmatic excision (either nearly complete (n = 13) or 3*3cm (n = 9)) and primary closure (Gore-Tex patch). Survival was further increased by moving to laryngeal mask airway ventilation (n = 15). Sham operated animals were used as controls (n = 6). Survivors (90 days) underwent chest X-Ray (scoliosis), measurements of maximum transdiaphragmatic pressure and breathing pattern (tidal volume, Pdi). Rates of herniation, lung histology and right hemi-diaphragmatic fiber cross-sectional area was measured. Results Rabbits surviving 90 days doubled their weight. Only one (8%) with a complete defect survived to 90 days. In the 3*3cm defect group all survived to 48 hours, however seven (78%) died later (16–49 days) from respiratory failure secondary to tracheal stricture formation. Use of a laryngeal mask airway doubled 90-day survival, one pup displaying herniation (17%). Cobb angel measurements, breathing pattern, and lung histology were comparable to sham. Under exertion, sham animals increased their maximum transdiaphragmatic pressure 134% compared to a 71% increase in patched animals (p<0.05). Patched animals had a compensatory increase in their right hemi-diaphragmatic fiber cross-sectional area (p<0.0001). Conclusions A primarily patched 3*3cm defect in growing rabbits, under laryngeal mask airway ventilation, enables adequate survival with normal lung function and reduced maximum transdiaphragmatic pressure compared to controls.

A reference for ductus venosus blood flow at 11-13+6 weeks of gestation.

Objective: To establish reference ranges for ductus venosus (DV) blood flow assessment obtained transabdominally at 11-13+6 weeks of gestation. Methods: A cross-sectional study was conducted on singleton pregnancies with a crown-rump length (CRL) ranging from 45 to 84 mm, normal fetus, and subsequent newborn birth weight appropriate for gestational age. Measurements of DV Doppler variables were performed by experienced sonographers: peak velocity during ventricular systole (S-wave) and diastole (D-wave), nadir during atrial contraction (A-wave), time-averaged maximum velocity (TAmax), pulsatility index for veins (PIV), and peak velocity index for veins (PVIV). Results: A total of 304 fetuses were included. The mean CRL was 60.7 ± 7.2 mm (range: 45.9-75.5). The mean nuchal translucency measurement was 1.4 ± 0.4 mm. The S-wave, D-wave, A-wave, and TAmax values varied significantly with gestational age (p < 0.05) and regression models were constructed for each variable. The remaining variables, systolic/atrial wave ratio, preload index, PVIV, and PIV, did not vary significantly with gestational age within this CRL range. Conclusion: Reference ranges for DV Doppler assessment were established in normal fetuses. These ranges may be a useful tool for evaluation of anueploidy and fetal cardiac function.

Prenatal diagnosis of complete trisomy 9 with a novel sonographic finding of heart calcification.

Complete trisomy 9 is a rare chromosomal disorder. The prenatal sonographic features of fetuses with complete trisomy 9 are nonspecific. There are also some reports showing rare features such as abnormal calcification in the liver and hypochondral region.1–4 Complete trisomy 9 was first described in 1973 from cultured lymphocytes in an infant with congenital heart defects, skeletal abnormalities, and severe dysmorphism.5 Most cases of complete trisomy 9 result in spontaneous first-trimester abortion. Fetuses who survive to term generally have a mosaic state.6,7 Since the prognosis of fetuses with complete trisomy 9 is poor, and the survival rate is very low, prenatal diagnosis of this condition is beneficial to provide useful information for genetic counseling and prenatal care. Sonography is a noninvasive and helpful tool in detecting this condition, especially when fetal karyotyping is unavailable. Although there are overlapping prenatal sonographic findings between trisomy 9 and trisomy 18, the main characteristic findings of complete trisomy 9 are cardiovascular defects, intrauterine growth restriction, genitourinary abnormalities, and limb anomalies. Craniofacial dysmorphism and a single umbilical artery can also be detected in some cases.8,9 Most reported cases were confirmed by fetal karyotyping, either from amniotic fluid or lymphocyte cultures. Here we report a new sonographic finding in a complete trisomy 9 case, which was confirmed postnatally by autopsy along with fetal karyotyping. This finding provides useful information, which will help in prenatal diagnosis of this lethal condition. A 37-year-old woman, gravida 4, para 2012, was referred to our institution at a gestational age of 16 weeks 5 days for amniocentesis due to advanced maternal age and a history of a child with trisomy 21. The first fetal sonographic examination showed a singleton fetus with a strawberry head shape, a moderately hyperechoic bowel, overlapping fingers, and a single umbilical artery. A fetal echocardiogram revealed situs solitus and abnormal left-axis deviation. Interestingly, abnormal cardiac calcification was also detected in both ventricular walls and the interventricular septum (Figure 1). The estimated fetal weight was appropriate for gestational age. Amniocentesis was subsequently performed, and fetal karyotyping showed 47,XX,+9 by the standard G-banding technique. The second sonographic examination was performed at 19 weeks’ gestation. Intrauterine growth restriction was not observed, and no additional physical anomalies were detected. Genetic counseling was provided to the family. Cordocentesis was performed, which confirmed the complete trisomy 9 female karyotype. Termination of pregnancy was performed at 21 weeks 5 days, after which an autopsy report indicated a female abortus weighing 270 g with multiple dysmorphic features, including a broad-based nose, hypertelorism, micrognathia, low-set ears, clenched hands, a 2-vessel cord, and an imperforate anus. The heart with calcification in both ventricular walls and interventic-

Comparison of transabdominal and transvaginal sonography in the diagnosis of placenta previa

To compare the accuracies of transabdominal sonography (TAS) and transvaginal sonography (TVS) in the diagnosis of placenta previa.

Normative weight-adjusted models for the median levels of first trimester serum biomarkers for trisomy 21 screening in a specific ethnicity

Objective To establish normative weight-adjusted models for the median levels of first trimester serum biomarkers for trisomy 21 screening in southern Thai women, and to compare these reference levels with Caucasian-specific and northern Thai models. Methods A cross-sectional study was conducted in 1,150 normal singleton pregnancy women to determine serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG) concentrations in women from southern Thailand. The predicted median values were compared with published equations for Caucasians and northern Thai women. Results The best-fitting regression equations for the expected median serum levels of PAPP-A (mIU/L) and free β- hCG (ng/mL) according to maternal weight (Wt in kg) and gestational age (GA in days) were: median PAPP−A=e[8.4454 − 0.01950 (Wt-55)+ 0.05747 (GA-87)], and median free β−hCG=e[3.6409 − 0.01703 (Wt-55)– 0.03345 (GA-87)]. Both equations were selected with a statistically significant contribution (p< 0.05). Compared with the Caucasian model, the median values of PAPP-A were higher and the median values of free β-hCG were lower in the southern Thai women. And compared with the northern Thai models, the median values of both biomarkers were lower in southern Thai women. Conclusion The study has successfully developed maternal-weight- and gestational-age-adjusted median normative models to convert the PAPP-A and free β-hCG levels into their Multiple of Median equivalents in southern Thai women. These models confirmed ethnic differences.

Modulation of the Early Host Response to Electrospun Polylactic Acid Matrices by Mesenchymal Stem Cells from the Amniotic Fluid

Purpose The reconstruction of congenital diaphragmatic hernia or other congenital soft tissue defects often requires implants. These can be either degradable or permanent, each having their advantages. Whatever type is being used, the host response induced by implants plays a crucial role to determine the outcome. Macrophages are pivotal during implant remodeling; they are plastic and acquire in response to environmental stimuli either an inflammatory status and mediate subsequent fibrosis or a regulatory status and facilitate functional remodeling. Matrices engineered with mesenchymal stem cells (MSCs) have the capacity to modulate the host immune reaction. MSCs are believed to promote constructive remodeling of the implant through a regulatory macrophage response among others. Herein, we evaluate this potential of MSC derived from the amniotic fluid (AF‐MSC), an interesting MSC type for neonatal reconstruction, on electrospun polylactic acid (PLA) scaffolds. Methods We seeded AF‐MSC at a density of 1.105/cm2 on electrospun PLA matrices and determined cell viability. In vivo, we used cell‐seeded or cell‐free PLA matrices for subcutaneous implantation in immune competent rats. The host immune response was evaluated by histomorphometry at 14 days postoperatively. Results The PLA matrix supported adherence and proliferation of AF‐MSC. Fourteen days after implantation, PLA matrices were well penetrated by inflammatory cells, new blood vessels, and collagen fibers. AF‐MSC‐seeded scaffolds were associated with a similar response yet with a decreased number of eosinophils, increased matrix degradation and collagen fiber deposition compared with controls. The amount of total macrophages and of M2‐subtype was similar for all animals. Conclusion Electrospun PLA matrices are a suitable substrate for short‐term culture of AF‐MSC. In rats, addition of AF‐MSC to PLA matrices modulates the host response after subcutaneous implantation, yet without a difference in macrophage profile compared with control.

Frontomaxillary facial angle in chromosomally normal Thai foetuses at 11 to 13 weeks 6 days’ gestation

Frontomaxillary facial (FMF) angle is the angle between upper part of the anterior end of the maxillary bone and the line along the frontal bone in the midfacial profile view. Based on several previous studies, FMF angle can be useful in screening Down syndrome foetuses, in which FMF angle is significantly larger than that in euploid foetuses. However, racial factors can influence the FMF angle as seen in the different normal ranges among ethnicities. Therefore, before the clinical application of the FMF angle, a reference range for its own population should firstly be developed. In this study, a Thai reference range of FMF angle has been established. The mean FMF angle in euploid foetuses with a 60-mm crown–rump length (CRL) was 81.07°, with 0.23° increase for each mm increase in CRL, consistent with those observed in Caucasian and Chinese populations. The measurement of FMF angle has good reproducibility.

Thrombin Generation by Fetoscopic Trauma to the Fetal Membranes: An in vivo and in vitro Study

Objective: We first aimed to investigate in vivo thrombin generation induced by fetoscopy, and second we used term membrane explants for measurement of thrombin generation, thrombin receptor location and induction of selected matrix metalloproteinases (MMPs) in tissue culture. Materials and Methods: In vivo study (37 cases): samples of amniotic fluid were taken at the beginning and end of fetoscopy (mean gestational age 26.7 weeks) and analyzed by ELISA for thrombin-antithrombin complexes. In vitro study: fetal membranes were put in culture and punctured for measurement of thrombin generation by calibrated automated thrombography and ELISA. Induction of MMP-9 and MMP-2 was analyzed by zymography. PAR-1 was localized by immunohistochemistry. Results: No significant increase in thrombin-antithrombin was measured in amniotic fluid obtained during fetoscopy. In vitro, thrombin generation induced by needle trauma of membrane cultures is correlated to the amount of plasma. Activity of MMP-9 but not MMP-2 was elevated in cultured membranes but could not be inhibited by a thrombin inhibitor. On histology, the thrombin receptor PAR-1 was located in the chorion and decidua, but not in the amnion. Discussion: Despite the influence of thrombin on punctured fetal membranes in vitro, the role of thrombin in iatrogenic preterm premature rupture of membranes is questionable.