A 4-year review of amniocentesis at a tertiary hospital in Ethiopia: an experience from a LMIC

1 1 2 3 4 A 4-year review of amniocentesis at a tertiary hospital in Ethiopia: an experience 5 from a LMIC 6 7 8 Haile G. Mekuria1*, Hilkiah K. Suga2†, Gadise Bekele3 9 10 1Department of Obstetrics and Gynecology, Myungsung Medical College/MCM 11 Comprehensive Specialized Hospital, Addis Ababa, Ethiopia 12 2Department of Research, Blue Health Medical Consultancy, Addis Ababa, Ethiopia 13 3Department of Biostatistics, Addis Continental Institute of Public Health, Addis Ababa, 14 Ethiopia 15 16 *First author 17 †Corresponding author: [email protected] . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. 2 18 Abstract 19 Background: Amniocentesis is a technique for withdrawing amniotic fluid from the 20 uterine cavity using a needle via a trans-abdominal approach. It has multiple diagnostic 21 and therapeutic uses such as prenatal genetic studies and amnioreduction for 22 polyhydramnios. The commonest indications are advanced maternal age and increased 23 risk on maternal serum screening. The objective of this study is to review the common 24 indications, outcomes and complications of amniocentesis at a tertiary hospital in 25 Ethiopia. 26 Methods: A retrospective cross-sectional study was conducted at a tertiary hospital in 27 Ethiopia. Data was collected from the Fetomaternal division’s log records and follow-up 28 charts during the time period of 2019 to 2022. All records of patients who had 29 amniocentesis done were included in the study. Socio-demographic information and 30 obstetric history and variables related to the procedures were retrieved. Descriptive 31 statistics was done using the software IBM Statistical Package for Social Sciences 32 (SPSS) version 25. 33 Results: A total of 35 patients’ records were reviewed. The mean maternal age was 32 34 years (range, 19 – 43 years). The mean gestational age was 20.9 weeks (SD ± 2.2). 35 The commonest indications for amniocentesis were previous history of Down syndrome 36 (11%), advanced maternal age (9%) and QUAD 1:200 for Down syndrome (6%). 37 Karyotype test was done in 29 of the 35 amniocentesis cases which was normal in 72% 38 of the cases, 17% had Trisomy-21 and 11% had Trisomy-18. Fifty-two percent of the 39 pregnancy had a live full term delivery and 25% of the cases terminated the pregnancy. 40 Conclusion: The most common indications for amniocentesis in Ethiopia were abnormal 41 ultrasound finding, advanced maternal age and abnormal QUAD test results. Around a 42 quarter of the genetic tests which were done after the procedure had chromosomal 43 abnormalities, from which, the majority were terminated. There was no complication 44 related to the procedure. 45 Keywords: amniocentesis, advanced maternal age, prenatal genetic study, 46 chromosomal abnormality, fetomaternal complication . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 3 47 Introduction 48 Amniocentesis is a technique for withdrawing amniotic fluid from the uterine cavity using 49 a needle via a trans-abdominal approach. Amniocentesis has been widely used since it 50 was first performed in 1956. Originally reported as a method of determining fetal sex in 51 utero, Fuchs and Riis then hypothesized that it could be possible to diagnose 52 chromosomal abnormalities in utero via this technique. By 1963, it had been confirmed 53 that the karyotype of fetal and amniotic cells are identical (1 – 3). 54 The most common diagnostic indications for obtaining amniotic fluid are prenatal 55 genetic studies and assessment of fetal lung maturity. Other indications include, but are 56 not limited to, evaluation of the fetus for infection, degree of hemolytic anemia, blood or 57 platelet type, hemoglobinopathy, and neural tube defects. Risks include spontaneous 58 abortion, infection, needle injuries, and preterm labor (4, 5). 59 Amniocentesis is also performed as a therapeutic procedure to remove excess amniotic 60 fluid, such as in symptomatic polyhydramnios or twin-twin transfusion syndrome, or to 61 reduce volume and pressure of amniotic fluid in cases of prolapsed fetal membranes in 62 the second trimester to facilitate placement of an emergency cerclage.(6, 7) 63 Since the late 1960s, amniocentesis has become a widely accepted method of 64 obtaining fetal genetic information (8). Amniocentesis for prenatal genetic studies is 65 technically possible at any gestational age after approximately 11 weeks of gestation, 66 but is optimally performed after 15 to 17 weeks of gestation. Procedures performed 67 before 15 weeks (ie, early amniocentesis) are associated with higher fetal loss and 68 complication rates, including culture failure, and should be avoided. Later procedures . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 4 69 can be problematic if termination of pregnancy is planned based upon abnormal results. 70 Although some pain is associated with amniocentesis, it is generally well tolerated 71 without the need for anesthesia (8, 9). 72 Maternal age over 35 is the most common indication for amniocentesis (10). It is 73 conventionally performed between 16 – 24 weeks. The chances of late-onset 74 abnormalities after 1st and 2nd-trimester ultrasound examinations are estimated at 75 5.5%-17% (11). 76 Counseling about the risk and benefit of the procedure is very important as some 77 women may decline the procedure if they don’t want to terminate the pregnancy 78 whatever the result is. Others, even if they don’t want to terminate the pregnancy, they 79 accept the procedure to prepare themselves for the care of the baby after delivery (12). 80 Prenatal chromosomal microarray analysis is recommended for a patient with a fetus 81 with one or more major structural abnormalities identified on ultrasonographic 82 examination and who is undergoing invasive prenatal diagnosis (13). 83 Even though the procedure is more than 6 decades old, as far as the authors search 84 goes, this report is the first of its kind from an experience located in the Eastern Africa. 85 This study aims to review the common indications and outcomes of prenatal diagnostic 86 amniocentesis and its complications at a tertiary center in Ethiopia. 87 Methods 88 A retrospective cross-sectional study was conducted at the Fetomaternal division, 89 Department of Obstetrics and Gynecology, MCM Comprehensive Specialized Hospital, . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 5 90 Addis Ababa, Ethiopia. The department is one of the few in the country that gives 91 prenatal amniocentesis service. Data was collected from the division’s log records and 92 follow-up charts which was abstracted from 2019 to 2022. Study period was from June 93 1st to 30 th, 2023. Records of all patients who had prenatal amniocentesis done during 94 the timeframe were included in the study. The following variables were collected: 95 indication, maternal age, gestational age, needle size, BMI, pregnancy outcome, result 96 of the genetic test, presence of vaginal bleeding post-procedure, presence of 97 amnionitis. The procedures were carried out by the same fetomaternal specialist using 98 the same ultrasound guided techniques. IBM Statistical Package for Social Sciences 99 (SPSS) version 25 was used to compute descriptive statistics. 100 Ethical approval was obtained prior to the data collection and the investigators did not 101 collect personal identification information of the patients. 102 Results 103 A total of 35 women had amniocentesis between 2019 and 2022 with the mean 104 maternal age was 32 years (range, 19 – 43 years). The mean gestational age was 20.9 105 weeks (SD ± 2.2, range 17 – 25) and mean maternal BMI was 21 kg/m2 (SD ± 2.4). In 106 23 patients, 20 Gauge needle was used and 22 Gauge was used in the others. The 107 needle insertion to the probe angle was perpendicular in 30 of the procedures (85%) 108 and parallel in 5 of the procedures (15%). 109 The commonest indications were previous history of down syndrome (11%), advanced 110 maternal age (9%), cleft lip (6%), history of Recurrent pregnancy loss or RPL (6%), . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 6 111 hydrocephalus (6%), non-immune hydrops (6%), omphalocele (6%), QUAD 1:200 for 112 down syndrome (6%). 113 Karyotype test was done in 29 of the 35 amniocentesis cases. Karyotype results were 114 normal in 72% of cases (21/29), Trisomy-21 in 17% (5/29) and Trisomy-18 in 11% 115 (3/29). Almost half (52%) of the cases had a live birth, 46% (16/35) had a term delivery 116 and 6% (2/35) had a preterm delivery. Stillbirth or miscarriage occurred in 17% (6/35), 117 25% (9/35) of the cases terminated the pregnancy and the outcome was not known in 118 6% (2/35) of the cases. Pathological ultrasonography has the highest positive detection 119 rate (30%) 120 Discussion 121 Amniocentesis is generally done after the 15th gestational week with a miscarriage risk 122 of less than 1% (14, 15). The risk of spontaneous fetal losses following amniocentesis 123 preformed before this gestational age increases (16). Likewise, the patients in our study 124 were between the gestational age of 17 and 25 weeks, which were under the accepted 125 gestational age range. 126 Currently twenty and twenty-two gauge needles are commonly used and in this study, 127 two-third of the procedure was done using a 20G needle. The larger needle size i.e. 128 20G is associated with significantly shorter duration of amniocentesis. However, there is 129 no significant difference in the intrauterine bleeding at the insertion site and fetal loss 130 (17, 18). Likewise, none of the patients in this study had documented intrauterine 131 bleeding in both groups (20G vs 22G). . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 7 132 A study done in South East China that did a retrospective analysis on more than 4700 133 patients who had an amniocentesis showed the commonest indications for 134 amniocentesis were increased risk on maternal serum screenings and advanced 135 maternal age. They are indications for 86% of the procedures (5). Another 5 year 136 reviews from Malaysia and China hospitals showed similar findings i.e. both indications 137 accounted for more than half of the total procedures (19, 20). Other common indications 138 include poor obstetric history, pathological ultrasonography findings and positive results 139 from non-invasive prenatal testing. However, in our study, the majority of indication for 140 amniocentesis was done due to the pathological ultrasonography findings (57% vs 12% 141 or 4%) followed by previous Down syndrome baby and increased risk on maternal 142 serum screenings, each accounted for 11% of the procedures. Advanced maternal age 143 was an indication in only 9% of cases. 144 Positive detection rate of pathological ultrasonography for chromosomal abnormalities is 145 less than 15% (19, 20). Noninvasive prenatal DNA testing has the highest positive 146 detection rate with greater than 40% (42% and 53%). In our study, pathological 147 ultrasonography has the highest positive detection rate (30%). 148 Conclusion 149 A review of the first 5 years of amniocentesis at our center showed that the most 150 common indication to the procedure was abnormal ultrasound finding. Advanced 151 maternal age and abnormal QUAD test results were also among the common 152 indications. Around a quarter of the genetic tests which were done after the procedure 153 had chromosomal abnormalities, from which, the majority were terminated. There was . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 8 154 no complication related to the procedure. Further study is required to understand more 155 fetomatenal complications of amniocentesis in Ethiopia. . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 9 156 Reference 157 (1) FUCHS F, RIIS P. Antenatal sex determination. Nature. 1956 Feb 18;177 158 (4503):330. doi: 10.1038/177330a0. PMID: 13297032. 159 (2) Connolly KA, Eddleman KA. Amniocentesis: A contemporary review. World J Obstet 160 Gynecol 2016; 5(1): 58-65 [DOI: 10.5317/wjog.v5.i1.58] 161 (3) Steele MW, Breg WR Jr. Chromosome analysis of human amniotic-fluid cells. 162 Lancet. 1966 Feb 19;1(7434):383-5. doi: 10.1016/s0140-6736(66)91387-0. 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CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 12 230 Table 1: A five year summary of genetic test results and indications for amniocentesis at 231 MCM Comprehensive Specialized Hospital, 2019 – 2022 Genetic test result Number of cases Percenta ge (denomina tor being the subtotal, %) Percentag e (denominat or being the grand total, %) Advanced maternal age 2 9.52 5.71 Pathological ultrasonography findings 12 57.14 34.28 History of recurrent pregnancy loss 1 4.76 2.86 Previous history of MR baby 1 4.76 2.86 Previous hx of Down Syndrome 4 19.05 11.43 Indication for amniocentesis QUAD 1:200 for Down Syndrome 1 4.76 2.86 Normal Karyotype Total 21 100 60 Indication for amniocentesis Pathological ultrasonography findings 5 100 14.29Trisomy 21 Total 5 100 14.29 Pathological ultrasonography findings 1 33.33 2.86 History of still birth 1 33.33 2.86 Indication for amniocentesis QUAD 1:10 for trisomy 18 1 33.33 2.86 Trisomy 18 Total 3 100 8.57 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 13 Advanced maternal age 1 16.67 2.86 Pathological ultrasonography findings 2 33.33 5.71 History of RPL 1 16.67 2.86 QUAD 1:150 for Down Syndrome 1 16.67 2.86 Indication for amniocentesis QUAD 1:200 for Down Syndrome 1 16.67 2.86 Not determine d Total 6 100 17.14 Grand total 35 100 232 233 234 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint 14 235 Table 2: Pregnancy outcomes and genetic test results of women who had 236 amniocentesis at MCM Comprehensive Specialized Hospital, 2019 – 2022 Genetic test result Normal Trisomy 18 or 21 Not determined Total Term delivery 12 0 4 16 Preterm delivery 2 0 0 2 Terminated 1 7 1 9 Still birth 5 1 0 6 Pregnancy outcome Unknown 1 0 1 2 Total 21 8 6 35 237 . CC-BY 4.0 International licenseIt is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint The copyright holder for thisthis version posted November 11, 2023. ; https://doi.org/10.1101/2023.11.10.23298380doi: medRxiv preprint