Utility of fetal facial markers on a second trimester genetic sonogram in screening for Down syndrome in a high-risk Thai population

Background To establish the reference ranges and evaluate the efficacy of the fetal facial sonomarkers prenasal thickness (PT), nasal bone length (NBL), PT/NBL ratio and NBL/PT ratio for Down syndrome screening in the second trimester of high-risk pregnancies using two-dimensional (2D) ultrasound. Methods A prospective study was done in Thai pregnant women at high risk for structural and chromosomal abnormalities between May 2018 and May 2019. The main exclusion criteria were any fetal anatomical anomaly detected on ultrasonography or postpartum examination, abnormal chromosome or syndrome other than Down syndrome. Ultrasounds were performed in 375 pregnant women at 14 to 22 weeks’ gestation and the fetal facial parameters were analyzed. Down syndrome results were confirmed by karyotyping. The reference ranges of these facial ultrasound markers were constructed based on the data of our population. The Down syndrome screening performance using these facial ultrasound markers was evaluated. Results In total, 340 euploid fetuses and 11 fetuses with Down syndrome met the inclusion criteria. The PT, NBL, and PT/NBL ratios in the euploid fetuses gradually increased with gestation progression while the NBL/PT ratio gradually decreased between 14–22 weeks’ gestation. The NBL, PT/NBL ratio, and NBL/PT ratio all had 100% sensitivity and PT had 91% sensitivity. These facial markers had 100% negative predictive value for Down syndrome screening in the second trimester. The Bland–Altman analysis showed the intra- and inter-observer variations of PT and NBL had high intraclass correlation coefficients (ICC) in both operators, with ICCs of 0.98 and 0.99 and inter-observer ICCs of 0.99 for both operators. Conclusion The facial ultrasound markers are very useful for second trimester Down syndrome screening in our population. These facial ultrasound markers were easily identifiable and highly consistent either intra- or inter-operator by using widely-available 2D ultrasound. However, the reference ranges for these markers need to be constructed based on individual populations. Trial registration Registration number: REC 61–029-12–3. Date of registration: 18 May 2018.

The femur too short? 1373 fetuses with short femur during second-trimester screening

Purpose A short fetal femur in prenatal diagnosis might be an indicator for intrauterine growth retardation (IUGR), a genetically determined small child (SGA) with or without associated fetal malformations and/or an adverse fetal outcome. Methods 1373 singleton pregnancies with a femoral length < 5th percentile detected between 1999 and 2015 during second-trimester screening in a tertiary prenatal diagnostic center were subjected to a descriptive retrospective analysis with regard to fetal characteristics as well as pregnancy outcome. Results 685 (49.9%) fetuses presented an isolated short femur, while 688 (50.1%) showed additional abnormalities. 293 (42.6%) of those were SGA babies without any malformation, while 395 (57.4%) had one or more severe anomaly of the following organ systems: 157 (11.5%) cardiovascular, 101 (7.4%) musculoskeletal, 82 (6.0%) urogenital, 72 (5.2%) cerebrocephalic, 50 (3.6%) gastrointestinal, and 5 (0.4%) thoracic. 75 (5.5%) of the fetuses showed chromosomal aberrations of which Trisomy 13, 18 and 21 were found in 2, 13 and 27 of the cases, respectively. Fetuses with associated malformations had a significantly lower live birth rate than those without (64.2% vs. 98.1%, p < 0.001); in addition, a higher rate of preterm births 36.6% vs. 11.3%, p < 0.001) and SGA babies (51.4% vs. 30.4%, p < 0.001) were observed in the first collective. Conclusion Diagnosis of a short fetal femur should lead to an extended organ screening; in the case of associated abnormalities, additional genetic testing has to be offered, as well as intensified pregnancy monitoring in pregnancies at risk for IUGR and/or preterm birth.

Second Trimester Fetal Loss Due to Citrobacter koseri Infection: A Rare Cause of Preterm Premature Rupture of Membranes (PPROM)

Citrobacter koseri is a facultative anaerobic, motile, non-spore-forming Gram-negative bacillus, which belongs to the family of Enterobacteriaceae. Severe infections due to Citrobacter spp. have been reported in the urinary tract, respiratory airways, intra-abdominal organs, skin and soft tissue, eye, bone, bloodstream, and central nervous system. In newborns, C. koseri is a well-known cause of meningitis, cerebral abscesses, brain adhesions, encephalitis, and pneumocephalus. Infection can be acquired through vertical maternal transmission or horizontal hospital settings; however, in many cases, the source is unknown. Preterm premature rupture of membranes (PPROM), caused by C. koseri, has rarely been described. Herein, we describe a case of PPROM at 16 weeks and 3 days of gestation, leading to anhydramnios. The parents opted for legal termination of the pregnancy, as the prognosis was very poor. C. koseri was isolated postmortem from a placental subamniotic swab and parenchymal sample, as well as fetal blood and lung. To the best of our knowledge, this is the first case of early second-trimester PPROM in which C. koseri infection was demonstrated.

The impact of prenatal screening tests on prenatal diagnosis in Taiwan from 2006 to 2019: a regional cohort study

Background The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan’s 14 years from 2006 to 2019. Methods The prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website. Results This regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively. Conclusion During the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased.

Postprandial Levels of Branched-chain and Aromatic Amino Acids Associate With Gestational Diabetes Mellitus

AimsSerum branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with obesity, insulin resistance and type 2 diabetes mellitus (T2DM). We want to investigate the levels of these amino acids in women with GDM and subsequently examine their changes in response to an oral glucose tolerance test (OGTT). Methods43 GDMs and 67 non-GDMs during their second trimester were recruited in this study. A 75-g OGTT was administered, and fasting, 1-h, and 2-h blood samples were obtained. Serum BCAA and AAA levels were measured by liquid chromatography-tandem mass spectrometry.ResultsThe differences of BCAAs and AAAs between women with GDM and controls during their second trimester were not evident during fasting, while became significant after a 75-g glucose load. Glucose ingestion decreased the levels of BCAAs and AAAs in both groups. Notably, GDMs showed a delayed and blunted decrease of these amino acids compared to non-GDMs. The risks of 2-h change of BCAAs and AAAs for GDM were significant.ConclusionsWe identified that the differences of BCAAs and AAAs between women with GDM and controls during their second trimester, which were not evident during fasting, could be provoked by performing OGTT.

β-hCG levels in second trimester as a predictor of gestational hypertension and preeclampsia

Background: Hypertensive disorders of pregnancy complicate up to 10% of pregnancies worldwide, and remain amongst the most significant and intriguing unsolved problems in obstetrics. The goal of this study is to test the hypothesis that women with high serum β-hCG levels in early pregnancy are at higher risk of developing gestational hypertension and preeclampsia.Methods: This is a prospective study done in 200 women between 13 and 20 weeks of gestation, selected randomly for this study. Serum β-hCG estimation was done by Sandwich chemiluminescence immunoassay method and calculated in multiple of median (MOM). They were followed till delivery for development of gestational hypertension and preeclampsia. Results were analysed statistically.Results: Out of 200 cases, 43 (21.5%) cases developed PIH. β-hCG levels were considered raised if the levels were >2 MOM. Out of 39 cases with beta HCG levels >2 MOM, 32 (82.1%) developed PIH whereas 7 (17.9%) remain normotensives against. Also, higher levels of beta HCG are associated with increased severity of PIH (p<0.000). The sensitivity was 82%, specificity was 93.2% and positive predictive value was 74.3%.Conclusions: The study conclude that elevated serum β-hCG levels in women with second trimester pregnancy indicates increased risk of gestational hypertension and preeclampsia and raised β-hCG levels are associated with severity of disease

Diagnostic accuracy of first and early second trimester multiple biomarkers for prediction of gestational diabetes mellitus: a multivariate longitudinal approach

Background Gestational Diabetes Mellitus (GDM) is an underlying cause of maternal and newborn morbidity and mortality all around the world. Timely diagnosis of GDM plays an important role in reducing its adverse consequences and burden. This study aimed to determine diagnostic accuracy of multiple indicators in complete blood count (CBC) test for early prediction of GDM. Methods In this prospective cohort study, the data from 600 pregnant women was analyzed. In the study sample, the two-step approach was utilized for the diagnosis of GDM at 24–28 weeks of gestation. We also used the repeated measures of hemoglobin (Hb), hematocrit (Hct), fasting blood sugar (FBS) and red blood cell count (RBC) in the first and early second trimesters of pregnancy as the longitudinal multiple indicators for early diagnosis of GDM. The classification of pregnant women to GDM and non-GDM groups was performed using a statistical technique based on the random-effects modeling framework. Results Among the sample, 49 women (8.2%) were diagnosed with GDM. In the first and early second trimester of pregnancy, the mean HcT, Hb and FBS of women with GDM was significantly higher than non-GDMs (P < 0.001). The concurrent use of multiple longitudinal data from HcT, Hb, RBC and FBS in the first and early second trimester of pregnancy resulted in a sensitivity, specificity and area under the curve (AUC) of 87%, 70% and 83%, respectively, for early prediction of GDM. Conclusions In general, our findings showed that the concurrent use of repeated measures data on Hct, Hb, FBS and RBC in the first and early second trimester of pregnancy might be utilized as an acceptable tool to predict GDM earlier in pregnancy.