{"paper_id":"6ff293a0-3465-42e6-9d8d-e030575167b5","body_text":"1\n1\n2\n3\n4 A 4-year review of amniocentesis at a tertiary hospital in Ethiopia: an experience \n5 from a LMIC\n6\n7\n8 Haile G. Mekuria1*, Hilkiah K. Suga2†, Gadise Bekele3\n9\n10 1Department of Obstetrics and Gynecology, Myungsung Medical College/MCM \n11 Comprehensive Specialized Hospital, Addis Ababa, Ethiopia \n12 2Department of Research, Blue Health Medical Consultancy, Addis Ababa, Ethiopia\n13 3Department of Biostatistics, Addis Continental Institute of Public Health, Addis Ababa, \n14 Ethiopia\n15\n16 *First author\n17 †Corresponding author: hilkms@gmail.com   \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \nNOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.\n\n2\n18 Abstract \n19 Background: Amniocentesis is a technique for withdrawing amniotic fluid from the \n20 uterine cavity using a needle via a trans-abdominal approach. It has multiple diagnostic \n21 and therapeutic uses such as prenatal genetic studies and amnioreduction for \n22 polyhydramnios. The commonest indications are advanced maternal age and increased \n23 risk on maternal serum screening. The objective of this study is to review the common \n24 indications, outcomes and complications of amniocentesis at a tertiary hospital in \n25 Ethiopia. \n26 Methods: A retrospective cross-sectional study was conducted at a tertiary hospital in \n27 Ethiopia. Data was collected from the Fetomaternal division’s log records and follow-up \n28 charts during the time period of 2019 to 2022. All records of patients who had \n29 amniocentesis done were included in the study. Socio-demographic information and \n30 obstetric history and variables related to the procedures were retrieved. Descriptive \n31 statistics was done using the software IBM Statistical Package for Social Sciences \n32 (SPSS) version 25. \n33 Results: A total of 35 patients’ records were reviewed. The mean maternal age was 32 \n34 years (range, 19 – 43 years). The mean gestational age was 20.9 weeks (SD ± 2.2). \n35 The commonest indications for amniocentesis were previous history of Down syndrome \n36 (11%), advanced maternal age (9%) and QUAD 1:200 for Down syndrome (6%). \n37 Karyotype test was done in 29 of the 35 amniocentesis cases which was normal in 72% \n38 of the cases, 17% had Trisomy-21 and 11% had Trisomy-18. Fifty-two percent of the \n39 pregnancy had a live full term delivery and 25% of the cases terminated the pregnancy. \n40 Conclusion: The most common indications for amniocentesis in Ethiopia were abnormal \n41 ultrasound finding, advanced maternal age and abnormal QUAD test results. Around a \n42 quarter of the genetic tests which were done after the procedure had chromosomal \n43 abnormalities, from which, the majority were terminated. There was no complication \n44 related to the procedure.\n45 Keywords: amniocentesis, advanced maternal age, prenatal genetic study, \n46 chromosomal abnormality, fetomaternal complication\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n3\n47 Introduction \n48 Amniocentesis is a technique for withdrawing amniotic fluid from the uterine cavity using \n49 a needle via a trans-abdominal approach. Amniocentesis has been widely used since it \n50 was first performed in 1956. Originally reported as a method of determining fetal sex in \n51 utero, Fuchs and Riis then hypothesized that it could be possible to diagnose \n52 chromosomal abnormalities in utero via this technique. By 1963, it had been confirmed \n53 that the karyotype of fetal and amniotic cells are identical (1 – 3).\n54 The most common diagnostic indications for obtaining amniotic fluid are prenatal \n55 genetic studies and assessment of fetal lung maturity. Other indications include, but are \n56 not limited to, evaluation of the fetus for infection, degree of hemolytic anemia, blood or \n57 platelet type, hemoglobinopathy, and neural tube defects. Risks include spontaneous \n58 abortion, infection, needle injuries, and preterm labor (4, 5). \n59 Amniocentesis is also performed as a therapeutic procedure to remove excess amniotic \n60 fluid, such as in symptomatic polyhydramnios or twin-twin transfusion syndrome, or to \n61 reduce volume and pressure of amniotic fluid in cases of prolapsed fetal membranes in \n62 the second trimester to facilitate placement of an emergency cerclage.(6, 7)\n63 Since the late 1960s, amniocentesis has become a widely accepted method of \n64 obtaining fetal genetic information (8). Amniocentesis for prenatal genetic studies is \n65 technically possible at any gestational age after approximately 11 weeks of gestation, \n66 but is optimally performed after 15 to 17 weeks of gestation. Procedures performed \n67 before 15 weeks (ie, early amniocentesis) are associated with higher fetal loss and \n68 complication rates, including culture failure, and should be avoided. Later procedures \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n4\n69 can be problematic if termination of pregnancy is planned based upon abnormal results. \n70 Although some pain is associated with amniocentesis, it is generally well tolerated \n71 without the need for anesthesia (8, 9).\n72 Maternal age over 35 is the most common indication for amniocentesis (10). It is \n73 conventionally performed between 16 – 24 weeks. The chances of late-onset \n74 abnormalities after 1st and 2nd-trimester ultrasound examinations are estimated at \n75 5.5%-17% (11). \n76 Counseling about the risk and benefit of the procedure is very important as some \n77 women may decline the procedure if they don’t want to terminate the pregnancy \n78 whatever the result is. Others, even if they don’t want to terminate the pregnancy, they \n79 accept the procedure to prepare themselves for the care of the baby after delivery (12).\n80 Prenatal chromosomal microarray analysis is recommended for a patient with a fetus \n81 with one or more major structural abnormalities identified on ultrasonographic \n82 examination and who is undergoing invasive prenatal diagnosis (13).\n83 Even though the procedure is more than 6 decades old, as far as the authors search \n84 goes, this report is the first of its kind from an experience located in the Eastern Africa. \n85 This study aims to review the common indications and outcomes of prenatal diagnostic \n86 amniocentesis and its complications at a tertiary center in Ethiopia. \n87 Methods\n88 A retrospective cross-sectional study was conducted at the Fetomaternal division, \n89 Department of Obstetrics and Gynecology, MCM Comprehensive Specialized Hospital, \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n5\n90 Addis Ababa, Ethiopia. The department is one of the few in the country that gives \n91 prenatal amniocentesis service. Data was collected from the division’s log records and \n92 follow-up charts which was abstracted from 2019 to 2022. Study period was from June \n93 1st to 30 th, 2023. Records of all patients who had prenatal amniocentesis done during \n94 the timeframe were included in the study. The following variables were collected: \n95 indication, maternal age, gestational age, needle size, BMI, pregnancy outcome, result \n96 of the genetic test, presence of vaginal bleeding post-procedure, presence of \n97 amnionitis. The procedures were carried out by the same fetomaternal specialist using \n98 the same ultrasound guided techniques. IBM Statistical Package for Social Sciences \n99 (SPSS) version 25 was used to compute descriptive statistics.\n100 Ethical approval was obtained prior to the data collection and the investigators did not \n101 collect personal identification information of the patients. \n102 Results \n103 A total of 35 women had amniocentesis between 2019 and 2022 with the mean \n104 maternal age was 32 years (range, 19 – 43 years). The mean gestational age was 20.9 \n105 weeks (SD ± 2.2, range 17 – 25) and mean maternal BMI was 21 kg/m2 (SD ± 2.4). In \n106 23 patients, 20 Gauge needle was used and 22 Gauge was used in the others. The \n107 needle insertion to the probe angle was perpendicular in 30 of the procedures (85%) \n108 and parallel in 5 of the procedures (15%). \n109 The commonest indications were previous history of down syndrome (11%), advanced \n110 maternal age (9%), cleft lip (6%), history of Recurrent pregnancy loss or RPL (6%), \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n6\n111 hydrocephalus (6%), non-immune hydrops (6%), omphalocele (6%), QUAD 1:200 for \n112 down syndrome (6%). \n113 Karyotype test was done in 29 of the 35 amniocentesis cases. Karyotype results were \n114 normal in 72% of cases (21/29), Trisomy-21 in 17% (5/29) and Trisomy-18 in 11% \n115 (3/29). Almost half (52%) of the cases had a live birth, 46% (16/35) had a term delivery \n116 and 6% (2/35) had a preterm delivery. Stillbirth or miscarriage occurred in 17% (6/35), \n117 25% (9/35) of the cases terminated the pregnancy and the outcome was not known in \n118 6% (2/35) of the cases. Pathological ultrasonography has the highest positive detection \n119 rate (30%)\n120 Discussion \n121 Amniocentesis is generally done after the 15th gestational week with a miscarriage risk \n122 of less than 1% (14, 15). The risk of spontaneous fetal losses following amniocentesis \n123 preformed before this gestational age increases (16). Likewise, the patients in our study \n124 were between the gestational age of 17 and 25 weeks, which were under the accepted \n125 gestational age range. \n126 Currently twenty and twenty-two gauge needles are commonly used and in this study, \n127 two-third of the procedure was done using a 20G needle. The larger needle size i.e. \n128 20G is associated with significantly shorter duration of amniocentesis. However, there is \n129 no significant difference in the intrauterine bleeding at the insertion site and fetal loss \n130 (17, 18). Likewise, none of the patients in this study had documented intrauterine \n131 bleeding in both groups (20G vs 22G).  \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n7\n132 A study done in South East China that did a retrospective analysis on more than 4700 \n133 patients who had an amniocentesis showed the commonest indications for \n134 amniocentesis were increased risk on maternal serum screenings and advanced \n135 maternal age. They are indications for 86% of the procedures (5). Another 5 year \n136 reviews from Malaysia and China hospitals showed similar findings i.e. both indications \n137 accounted for more than half of the total procedures (19, 20). Other common indications \n138 include poor obstetric history, pathological ultrasonography findings and positive results \n139 from non-invasive prenatal testing. However, in our study, the majority of indication for \n140 amniocentesis was done due to the pathological ultrasonography findings (57% vs 12% \n141 or 4%) followed by previous Down syndrome baby and increased risk on maternal \n142 serum screenings, each accounted for 11% of the procedures. Advanced maternal age \n143 was an indication in only 9% of cases.   \n144 Positive detection rate of pathological ultrasonography for chromosomal abnormalities is \n145 less than 15% (19, 20). Noninvasive prenatal DNA testing has the highest positive \n146 detection rate with greater than 40% (42% and 53%). In our study, pathological \n147 ultrasonography has the highest positive detection rate (30%). \n148 Conclusion \n149 A review of the first 5 years of amniocentesis at our center showed that the most \n150 common indication to the procedure was abnormal ultrasound finding. Advanced \n151 maternal age and abnormal QUAD test results were also among the common \n152 indications.  Around a quarter of the genetic tests which were done after the procedure \n153 had chromosomal abnormalities, from which, the majority were terminated. There was \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n8\n154 no complication related to the procedure. Further study is required to understand more \n155 fetomatenal complications of amniocentesis in Ethiopia.\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n9\n156 Reference\n157 (1) FUCHS F, RIIS P. Antenatal sex determination. Nature. 1956 Feb 18;177 \n158 (4503):330. doi: 10.1038/177330a0. PMID: 13297032.\n159 (2) Connolly KA, Eddleman KA. Amniocentesis: A contemporary review. World J Obstet \n160 Gynecol 2016; 5(1): 58-65 [DOI: 10.5317/wjog.v5.i1.58]\n161 (3) Steele MW, Breg WR Jr. Chromosome analysis of human amniotic-fluid cells. \n162 Lancet. 1966 Feb 19;1(7434):383-5. doi: 10.1016/s0140-6736(66)91387-0. PMID: \n163 4159775.\n164 (4) Bornstein E, Lenchner E, Donnenfeld A, Barnhard Y, Seubert D, Divon MY. \n165 Advanced maternal age as a sole indication for genetic amniocentesis; risk-benefit \n166 analysis based on a large database reflecting the current common practice. J Perinat \n167 Med. 2009;37(2):99-102. doi: 10.1515/JPM.2009.032. PMID: 18999912. \n168 (5) Tao H, Xiao J, Yang C, Wang J, Tang Y, Guo C, Wang J. Retrospective analysis of \n169 4761 cases who underwent amniocentesis in southeast China. J Obstet Gynaecol. 2018 \n170 Jan;38(1):38-41. doi: 10.1080/01443615.2017.1326887. Epub 2017 Aug 1. PMID: \n171 28764586.\n172 (6) Erfani H, Diaz-Rodriguez GE, Aalipour S, Nassr A, Rezaei A, Gandhi M, Mendez-\n173 Figueroa H, Aagaard KM, Shamshirsaz AA. Amnioreduction in cases of \n174 polyhydramnios: Indications and outcomes in singleton pregnancies without fetal \n175 interventions. Eur J Obstet Gynecol Reprod Biol. 2019 Oct;241:126-128. doi: \n176 10.1016/j.ejogrb.2019.05.019. 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PMID: 18310360.\n205 (15) Salomon LJ, Sotiriadis A, Wulff CB, Odibo A, Akolekar R. Risk of miscarriage \n206 following amniocentesis or chorionic villus sampling: systematic review of literature and \n207 updated meta-analysis. Ultrasound Obstet Gynecol. 2019 Oct;54(4):442-451. doi: \n208 10.1002/uog.20353. Epub 2019 Sep 6. PMID: 31124209.\n209 (16) Saltvedt S, Almström H. Fetal loss rate after second trimester amniocentesis at \n210 different gestational age. Acta Obstet Gynecol Scand. 1999 Jan;78(1):10-4. PMID: \n211 9926885.\n212 (17) Athanasiadis A, Petrakis P, Mikos T. Comparison of perinatal outcome after 2nd \n213 trimester amniocentesis using 22G and 20G needle. Hippokratia. 2017 Jan-\n214 Mar;21(1):60. PMID: 29904263; PMCID: PMC5997025.\n215 (18) Athanasiadis AP, Pantazis K, Goulis DG, Chatzigeorgiou K, Vaitsi V, \n216 Assimakopoulos E, Tzevelekis F, Tsalikis T, Bontis JN. Comparison between 20G and \n217 22G needle for second trimester amniocentesis in terms of technical aspects and short-\n218 term complications. Prenat Diagn 2009; 29: 761-765 [PMID: 19412914 DOI: \n219 10.1002/pd.2283]\n220 (19) Jummaat F, Ahmad S, Mohamed Ismail NA. 5-Year review on amniocentesis and \n221 its maternal fetal complications. Horm Mol Biol Clin Investig. 2019 Sep \n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n11\n222 20;40(2):/j/hmbci.2019.40.issue-2/hmbci-2019-0006/hmbci-2019-0006.xml. doi: \n223 10.1515/hmbci-2019-0006. PMID: 31539354.\n224 (20) Liu Y, Sun XC, Lv GJ, Liu JH, Sun C, Mu K. Amniotic fluid karyotype analysis and \n225 prenatal diagnosis strategy of 3117 pregnant women with amniocentesis indication. J \n226 Comp Eff Res. 2023 May 31;12(6):e220168. doi: 10.57264/cer-2022-0168. Epub ahead \n227 of print. PMID: 37256256; PMCID: PMC10402904.\n228\n229\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n12\n230 Table 1: A five year summary of genetic test results and indications for amniocentesis at \n231 MCM Comprehensive Specialized Hospital, 2019 – 2022 \nGenetic test result Number \nof cases\nPercenta\nge \n(denomina\ntor being \nthe \nsubtotal, \n%)\nPercentag\ne \n(denominat\nor being the \ngrand total, \n%)\nAdvanced maternal \nage\n2 9.52 5.71\nPathological \nultrasonography \nfindings\n12 57.14 34.28\nHistory of recurrent \npregnancy loss\n1 4.76 2.86\nPrevious history of \nMR baby\n1 4.76 2.86\nPrevious hx of Down \nSyndrome\n4 19.05 11.43\nIndication for \namniocentesis\nQUAD 1:200 for Down \nSyndrome\n1 4.76 2.86\nNormal \nKaryotype\nTotal 21 100 60\nIndication for \namniocentesis\nPathological \nultrasonography \nfindings\n5 100 14.29Trisomy \n21\nTotal 5 100 14.29\nPathological \nultrasonography \nfindings\n1 33.33 2.86\nHistory of still birth 1 33.33 2.86\nIndication for \namniocentesis\nQUAD 1:10 for \ntrisomy 18\n1 33.33 2.86\nTrisomy \n18\nTotal 3 100 8.57\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n13\nAdvanced maternal \nage\n1 16.67 2.86\nPathological \nultrasonography \nfindings\n2 33.33 5.71\nHistory of RPL 1 16.67 2.86\nQUAD 1:150 for Down \nSyndrome\n1 16.67 2.86\nIndication for \namniocentesis\nQUAD 1:200 for Down \nSyndrome\n1 16.67 2.86\nNot \ndetermine\nd\nTotal 6 100 17.14\nGrand total 35 100\n232\n233\n234\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint \n\n14\n235 Table 2: Pregnancy outcomes and genetic test results of women who had \n236 amniocentesis at MCM Comprehensive Specialized Hospital, 2019 – 2022\nGenetic test result\nNormal Trisomy \n18 or 21\nNot \ndetermined \nTotal\nTerm delivery 12 0 4 16\nPreterm delivery 2 0 0 2\nTerminated 1 7 1 9\nStill birth 5 1 0 6\nPregnancy \noutcome\nUnknown 1 0 1 2\nTotal 21 8 6 35\n237\n . CC-BY 4.0 International licenseIt is made available under a \n is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint \nThe copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint","source_license":"CC-BY-4.0","license_restricted":false}