
INVASIVE GENETIC STUDIES IN A MULTIPLE PREGNANCY Antsaklis A* *Corresponding Author: Professor Aris Antsaklis, 1st Department of Obstetrics & Genecology, Division of Maternal Fetal Medicine, University of Athens, “Alexandra” Maternity Hospital, Lampsakou 11, Athens 115 28, Greece; Tel.: +30-210-77-08-749/+30-210-82-666; Fax: +30-210-77-19-271; E-mail: arisants@otenet.gr page: 41
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THE GREEK EXPERIENCE
In the last 15 years, 372 patients with multiple pregnancies underwent genetic amniocentesis, of which 365 were twin pregnancies. One was lost to follow-up, 15 are ongoing pregnancies, and we present the data on 347 pregnancies. All patients has an ultrasound examination before the procedure in order to localize the placental site, the fetal position and to determine chorionicity.
The procedure was performed between the 11th and 23rd weeks’ gestation (mean gestational age 17.2 weeks). In seven cases, amniocentesis was performed before 14 completed weeks (first trimester amniocentesis) and in the remaining 340, between the 16th and 23rd week (second trimester amniocentesis) under ultrasound guidance. Patients were 19-52 years old (mean maternal age 36.18 years).
All procedures were performed with the double entry technique, using a 22 gauge needle, and 20 mL of amniotic fluid was successfully withdrawn from each sac. In 96 cases, both placentas were posterior, in 110 cases, both placentas were anterior, and in the remaining 141 there was one anterior and one posterior placenta. The rates of miscarriage were 2.08% (2/96).
In the group of 340 second trimester amniocentesis, two pregnancies were terminated [one because of homozygous b-thalassemia (thal) and one because of severe TTTS]. Six women underwent selective feticide (two because of trisomy 21, one because of 47XXX, two because of homozygous b-thal and one because of neural tube defect). One patient delivered a healthy live birth at 30 weeks and there was one neonatal death of a term baby due to a congenital heart defect. In this group 62.5% of pregnancies resulted in one live birth.
In the 332 remaining second trimester amniocentesis patients there were 14 miscarriages (4.21%), half of which occurred in the first 3 weeks after the procedure. The rate of pre-term delivery, before 32 weeks and before 35 weeks, was 11.94 and 32.07%, respectively. The perinatal loss rate, before and after 28 weeks, was 5.87 and 3.20%, respectively. The neonatal mortality rate, before and after 28 weeks, was 1.26 and 1.78%, respectively. Of the 332 pregnancies 94.58% resulted in at least one live birth.
During the same period, 74 CVS procedures were performed in multiple pregnancies. Six cases were lost to follow-up and we present the data of the remaining 38 cases. The procedure was performed transabdominally in all cases between the 9th and 15th week of gestation (mean maternal age 30.7 years, and the rate of repeat procedure was 11.76% (8/68). Five procedures were performed in pregnancies with more than two fetuses (four triplets and one quadruplet pregnancies) and the indications were b-thal [4] and advanced maternal age [1]. There were six fetuses affected by homozygous b-thal and two fetuses affected by trisomy 21; in all cases selective feticide was carried out at less than 14 weeks’ gestation. In this group, there were two spontaneous abortions at 20 and 21 weeks’ gestation (40%), and one patient delivered prematurely at 34 weeks (33.33%).
Chorionic villus sampling was were performed in 63 twin pregnancies. The indications were increased risk of chromosomal abnormality in 10 cases (includes advanced maternal age, anxiety, increased nuchal translucency and family history of trisomy 21), and increased risk of genetic syndromes of structural anomalies in 53 women (Duchenne syndrome, plenylketonuria, b-thal, structural anomalies).
In seven cases, the parents decided to terminate the pregnancy: six pregnancies because both fetuses had homozygous b-thal, and in one case of phenylketonuria the pregnancy was terminated before results became available. In twelve cases with one fetus affected by homozygous b-thal, selective feticide was carried out between 11 and 16 weeks’ gestation. One pregnancy (1/12; 8.33%) miscarried at 16 weeks, and two patients delivered healthy neonates (2/11, 18.18%) before 32 weeks. There were no other cases of fetal loss.
In the remaining 44 twin pregnancies, there were two miscarriages at 10 and 22 weeks’ gestation, respectively (2/44, 2.27%). The rate of pre-term delivery, before 32 and 35 weeks’ gestation, was 16.66% (7/42) and 23.80% (10/42), respectively. The perinatal loss, before and after 28 weeks’ gestation, was 9.09% (8/88) and 1.25% (1/80), respectively. Overall, 42 women (95.45%) delivered at least on healthy live baby.
Between 1977 and 2000, we performed 89 fetal blood-sampling procedures in twin pregnancies. Five cases were lost to follow-up, and we present the data of 84 cases. The patients were between 20-44 years old (mean age 28.3) and the procedures were performed between 18 and 29 weeks’ gestation (mean 20.3 weeks). For the first 28 cases, fetoscopy was carried out for fetal blood sampling, whereas after 1985, we switched to ultrasound guided cordocentesis, except in seven cases, where cardiocentesis was performed. The indications for fetal blood sampling in 61 cases was the risk for hemoglobinopathies, advanced maternal age (two cases), increased risk for congenital infection (two cases) and there was suspicion of fetal defects in the present pregnancy in seven cases.
Termination of the pregnancy was carried out in 17 cases. In nine cases both fetuses were affected by homozygous -thal, and in one case one fetus had severe obstructive uropathy and the other had hydrocephaly. In six cases only one fetus was affected, four cases by homozygous -thal, one case by trisomy 21, and one case by bowel obstruction; and the parents opted for termination. One patient had termination of her pregnancy because of chorioamnionitis.
Selective feticide was performed in 12 patients between 20 and 29 weeks’ gestation. There were 10 fetuses affected by b-thal, one fetus with a chromosomal abnormality (47XXY), and one with pulmonary hypoplasia. No miscarriages occurred in this group. The rate of pre-term delivery, before 32 and 35 weeks, was 41.66 and 50%, respectively. In the remaining 55 pregnancies there were two miscarriages, at 20 and 23 weeks’ gestation (3.92%). The rate of pre-term delivery, before 32 and 35 weeks, was 16.98 and 28.30%, respectively. The perinatal mortality rate, before and after 28 weeks, was 8.18 and 5.94%, respectively. Overall, 90.09% of women had at least one live baby.
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