Prenatally Diagnosed Rare Trisomy 16 Mosaicism in Human Amniotic Fluid Cells in the Second Trimester: A Case Report
Dev Reprod. 2018 Jun;22(2):199-203. doi: 10.12717/DR.2018.22.2.199. Epub 2018 Jun 30.
Kim SR1, Choi EJ1, Kim YJ1, Kim TY2, Lee YJ1.
Abstract Although trisomy 16 is commonly detected in spontaneous abortions and accounts for over 30% of cases of autosomal trisomy detected after spontaneous abortion, trisomy 16 mosaicism is rarely detected by amniocentesis in the second trimester. Here, we report a case of level III trisomy 16 mosaicism (47,XX,+16/46,XX) diagnosed by cytogenetic analysis of independently cultured amniotic fluid cells. The female baby was delivered at full term with low birth weight and intrauterine growth retardation, and interestingly, her karyotype was normal (46,XX). Given the difficulty in predicting the outcomes of fetuses with this mosaicism, it is recommended to inform the possibility of mosaicisms including this trisomy 16 mosaicism during prenatal genetic diagnosis and genetic counseling for parents. KEYWORDS: Amniocentesis; Mosaicism; Prenatal cytogenetic diagnosis; Trisomy 16 PMID: 30023470 PMCID: PMC6048302 DOI: 10.12717/DR.2018.22.2.199
Change in rates of prenatal tests for chromosomal abnormality over a 12-year period in women of advanced maternal age
Obstet Gynecol Sci. 2018 Jul;61(4):453-460. doi: 10.5468/ogs.2018.61.4.453. Epub 2018 Jun 19.
Kim SM1, Kim HH1, Han YJ1, Choi JS1, Ryu HM1, Yang S2, Kim MH1. Author information
OBJECTIVE: In 2007, the American College of Obstetricians and Gynecologists (ACOG) recommended that all pregnant women be offered screening or diagnostic tests for chromosomal abnormalities regardless of their age. Noninvasive prenatal testing (NIPT) for common chromosomal aneuploidies was introduced as a screening test in case of high-risk pregnancies. We assessed the rates of prenatal tests in women aged 35 years and older. METHODS: A retrospective study was conducted to compare the rates of amniocentesis, chorionic villus sampling (CVS), serum screening, and NIPT from January 2005 through March 2017 in women aged 35 years and older. We divided the initial 12 months after NIPT introduction into 4-month intervals, beginning in April 2016 through March 2017. RESULTS: The rates of amniocentesis were 56% before the ACOG statement, 38% between the ACOG statement and NIPT introduction, and 10% after NIPT introduction (P=0.001). The rates of CVS during the same periods were 0.5%, 2.1%, and 4.3% (P=0.016), respectively. The rates of serum screening were 44.2%, 61.3%, and 55.1% (P=0.049), respectively. During the 3 quarters after NIPT introduction, the rates of amniocentesis were 16.2%, 12.3%, and 7.3% (P=0.002), respectively; the rates of serum screening were 62%, 54%, and 46% (P=0.03), respectively; and the rates of NIPT were 19.9%, 30.3%, and 39.5% (P=0.007), respectively. The rates of CVS over the same periods were not significantly different. CONCLUSION: The ACOG statement and NIPT introduction significantly decreased the rate of amniocentesis in women of advanced maternal age. NIPT also reduced the rate of serum screening. KEYWORDS: Maternal age; Noninvasive prenatal testing; Prenatal diagnosis PMID: 30018899 PMCID: PMC6046356 DOI: 10.5468/ogs.2018.61.4.453
DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures
Ultraschall Med. 2018 Jul 12. doi: 10.1055/a-0631-8898. [Epub ahead of print]
[Article in English, German; Abstract available in German from the publisher]
Kozlowski P1, Burkhardt T2, Gembruch U3, Gonser M4, Kähler C5, Kagan KO6, von Kaisenberg C7, Klaritsch P8, Merz E9, Steiner H10, Tercanli S11, Vetter K12, Schramm T12. Author information Abstractin English, German First-trimester screening between 11 + 0 and 13 + 6 weeks with qualified prenatal counseling, detailed ultrasound, biochemical markers and maternal factors has become the basis for decisions about further examinations. It detects numerous structural and genetic anomalies. The inclusion of uterine artery Doppler and PlGF screens for preeclampsia and fetal growth restriction. Low-dose aspirin significantly reduces the prevalence of severe preterm eclampsia. Cut-off values define groups of high, intermediate and low probability. Prenatal counseling uses detection and false-positive rates to work out the individual need profile and the corresponding decision: no further diagnosis/screening - cell-free DNA screening - diagnostic procedure and genetic analysis. In pre-test counseling it must be recognized that the prevalence of trisomy 21, 18 or 13 is low in younger women, as in submicroscopic anomalies in every maternal age. Even with high specificities, the positive predictive values of screening tests for rare anomalies are low. In the general population trisomies and sex chromosome aneuploidies account for approximately 70 % of anomalies recognizable by conventional genetic analysis. Screen positive results of cfDNA tests have to be proven by diagnostic procedure and genetic diagnosis. In cases of inconclusive results a higher rate of genetic anomalies is detected. Procedure-related fetal loss rates after chorionic biopsy and amniocentesis performed by experts are lower than 1 to 2 in 1000. Counseling should include the possible detection of submicroscopic anomalies by comparative genomic hybridization (array-CGH). At present, existing studies about screening for microdeletions and duplications do not provide reliable data to calculate sensitivities, false-positive rates and positive predictive values.
PMID 30001568 DOI: 10.1055/a-0631-8898
The yield and complications of amniocentesis performed after 24 weeks of gestation
Arch Gynecol Obstet. 2017 May 24. doi: 10.1007/s00404-017-4408-7. [Epub ahead of print]
Geffen KT1,2, Ben-Zvi O3,4, Weitzner O3,4, Peleg A5, Biron-Shental T3,4, Sukenik-Halevy R3,4,6.
PURPOSE: This study assessed the use and complications of late amniocentesis (AC) and analyzed factors that affect complication rate. METHODS: A retrospective analysis of 167 genetic AC performed after 24 weeks during a 10-year period in two medical centers was conducted. Data regarding the indications for AC, genetic work-up, and pregnancy outcomes were retrieved from patient medical records and telephone-based questionnaires. RESULTS: Mean gestational age (GA) at the time of AC was 31.7 ± 2.7 weeks; 104 procedures were performed at ≤32 weeks, including 24 at ≤30 weeks. The overall pregnancy complication rate occurring at any time after the procedure was 6.6% (11). Of these, 4.8% (8) occurred within a month after AC, including 2.4% (4) that occurred within a week. An additional three occurred after 30 days. There were no differences in the total complication rate and in the rate of specific complications of procedures performed at ≤32 weeks or at ≤30 weeks. Maternal age did not affect outcomes. Genetic testing was abnormal in five cases (3%). Amniocyte culture failed in 3 cases (2.3%), with no technical failures in 52 chromosomal microarray tests. CONCLUSION: The complication rate of AC performed after 24 weeks was 4.8%, which is significantly higher than that of second trimester AC. GA and maternal age did not affect the complication rate. KEYWORDS: Chromosomal microarray; Complications; Genetic testing; Late amniocentesis; Third trimester amniocentesis PMID 28540575 DOI: 10.1007/s00404-017-4408-7
Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy
PLoS One. 2016 Apr 12;11(4):e0152740. doi: 10.1371/journal.pone.0152740. eCollection 2016.
Orczyk-Pawilowicz M1, Jawien E2, Deja S3, Hirnle L4, Zabek A2, Mlynarz P2.
Metabolic profiles of amniotic fluid and maternal blood are sources of valuable information about fetus development and can be potentially useful in diagnosis of pregnancy disorders. In this study, we applied 1H NMR-based metabolic profiling to track metabolic changes occurring in amniotic fluid (AF) and plasma (PL) of healthy mothers over the course of pregnancy. AF and PL samples were collected in the 2nd (T2) and 3rd (T3) trimester, prolonged pregnancy (PP) until time of delivery (TD). A multivariate data analysis of both biofluids reviled a metabolic switch-like transition between 2nd and 3rd trimester, which was followed by metabolic stabilization throughout the rest of pregnancy probably reflecting the stabilization of fetal maturation and development. The differences were further tested using univariate statistics at α = 0.001. In plasma the progression from T2 to T3 was related to increasing levels of glycerol, choline and ketone bodies (3-hydroxybutyrate and acetoacetate) while pyruvate concentration was significantly decreased. In amniotic fluid, T2 to T3 transition was associated with decreasing levels of glucose, carnitine, amino acids (valine, leucine, isoleucine, alanine, methionine, tyrosine, and phenylalanine) and increasing levels of creatinine, succinate, pyruvate, choline, N,N-dimethylglycine and urocanate. Lactate to pyruvate ratio was decreased in AF and conversely increased in PL. The results of our study, show that metabolomics profiling can be used to better understand physiological changes of the complex interdependencies of the mother, the placenta and the fetus during pregnancy. In the future, these results might be a useful reference point for analysis of complicated pregnancies. PMID 27070784
Proteomic Biomarkers in Second Trimester Amniotic Fluid That Identify Women Who Are Destined to Develop Preeclampsia
Reprod Sci. 2012 Apr 24. [Epub ahead of print]
Oh KJ, Park JS, Norwitz ER, Kim SM, Kim BJ, Park CW, Jun JK, Syn HC.
Objectives: This study investigated whether proteomic analysis of amniotic fluid (AF) in the early second trimester can be used to predict the development of preeclampsia. Methods: Amniotic fluid samples were collected at the time of genetic amniocentesis (15-19 weeks of gestation) from women who subsequently developed preeclampsia and from gestational age-matched normotensive controls (n = 10 for each). Amniotic fluid samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, sodium dodecyl sulfate polyacrylamide gel coupled with in-gel tryptic digestion, electrospray ionization tandem mass spectrometry (MS/MS), immunodepletion assays, and enzyme-linke immunosorbent assay. Results: Five proteomic biomarkers were identified, which were differentially expressed in women who subsequently developed preeclampsia compared with those women who did not; four of these peaks were significantly upregulated (mass-to-charge ratio of 9080 [P = .006], 14 045 [P = .010], 14 345 [P = .049], and 28 087 [P = .006]) and one was significantly downregulated (mass-to-charge ratio of 4679 [P = .014]) in women who subsequently developed preeclampsia. Using electrospray ionization MS/MS and immunodepletion assays, two protein peaks were identified as albumin fragment and apolipoprotein A-I. Conclusions: Using proteomic technology, this study identified protein biomarkers that are differentially expressed in the early second trimester AF from women who subsequently develop preeclampsia compared with women who remained normotensive. Early identification of women at risk of developing preeclampsia will allow clinicians to better optimize maternal and perinatal outcomes.
Mid-trimester amniotic fluid concentrations of the proinflammatory cytokines IL-6, IL-8, TNF-α, and lipopolysaccharide binding protein in normal pregnancies: a prospective evaluation according to parity, gestational age, and fetal gender
J Perinat Med. 2011 Jul;39(4):403-9. Epub 2011 Jun 24.
Bamberg C, Fotopoulou C, Linder M, Roehr CC, Dudenhausen JW, Henrich W, Kalache K. Source Department of Obstetrics, Charité-University Hospital, Berlin, Germany.
Abstract Objective: To assess mid-trimester amniotic fluid concentrations of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and lipopolysaccharide binding protein (LBP) in pregnancies with normal outcome and correlate them with gestational week (GW), parity, and fetal gender. Methods: Cytokine concentrations were measured within a week of amniocentesis during GW 15+0 to 20+6 and correlated with GW at birth, parity, and fetal gender. Results: After exclusion of women with an adverse pregnancy outcome or those lost to follow-up, 273 consecutive patients were evaluated (median parity: 1; range: 0-5). Ranges for IL-6, IL-8, TNF-α, and LBP were 4.9-2620 pg/mL, 36.2-5843 pg/mL, 8.0-28.2 pg/mL, and 0.06-1.9 μg/mL, respectively. IL-6, IL-8, and LBP values did not respectively differ among time points, but TNF-α values did between the 15(th) and 16(th) and the 15(th) and 18(th) weeks of gestation (P<0.05). No significant correlations between cytokine levels and parity or fetal gender were identified. Conclusions: Cytokine concentrations in amniotic fluid during the mid-trimester did not differ with parity or fetal gender. IL-6, IL-8, and LBP levels appeared stable with GW, whereas GW significantly influenced TNF-α concentrations. Further analyses are warranted to establish the role of cytokines in predicting adverse pregnancy outcomes.
Increased fetal plasma and amniotic fluid erythropoietin concentrations: markers of intrauterine hypoxia
Neonatology. 2009;95(2):105-16. doi: 10.1159/000153094. Epub 2008 Sep 6.
Teramo KA, Widness JA. Source Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland. firstname.lastname@example.org
Tissue hypoxia is the major stimulus of erythropoietin (EPO) synthesis in fetuses and adults. Since EPO does not cross the placenta and is not stored, fetal plasma and amniotic fluid levels indicate EPO synthesis and elimination. Acutely, the rate and magnitude of the increase in plasma EPO levels correlate with the intensity of hypoxia. Amniotic fluid EPO levels correlate with cord plasma levels in normal and abnormal pregnancies, with fetal plasma EPO levels in humans averaging 2.6 times higher than the corresponding amniotic fluid EPO levels. Recent experimental and clinical studies demonstrate that EPO has neuroprotective effects related to its anti-apoptotic and vascular growth-promoting properties. Although under basal conditions the fetal kidneys are the main site of EPO production, during hypoxia recent experimental data indicate an important role of the placenta. Amniotic fluid EPO levels have been shown to increase exponentially during fetal hypoxia in preeclamptic, diabetic and Rh-immunized pregnancies, to correlate inversely with cord blood pH, pO(2) and base excess and to predict neonatal morbidities and NICU admission. As an indicator of chronic intrauterine hypoxia, fetal EPO measurements have increased our knowledge about the pathogenesis and importance of intrauterine growth restriction, macrosomia, diabetic pregnancy, prolonged pregnancy, meconium staining, fetal hemorrhage, fetal anemia, maternal smoking and alcohol consumption, abnormal fetal heart rate and abnormal Doppler flow patterns. While the clinical utility of fetal amniotic fluid and plasma EPO measurements in the management of high-risk pregnancies and their offspring is promising, adequately powered clinical trials are urgently needed.