Delivery of a severely anaemic fetus after partial molar pregnancy: clinical and ultrasonographic findings

C.C. Hsieh1,3, T.T. Hsieh1, C. Hsueh2, D.M. Kuo1, L.M. Lo1 and T.H. Hung1

1 Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, 2 Department of Pathology, Chang Gung Memorial Hospital and Medical School of Chang Gung University, Taipei, Taiwan, Republic of China


    Abstract
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
The incidence of a normal live fetus and a partial molar placenta is extremely rare. Although triploidy is the most frequent association, a fetus with normal karyotype can survive in cases of partial molar pregnancy. We report a case of partial molar placenta in which a live female baby was delivered at 32 weeks gestation by a 30-year-old woman. At the 18th week, ultrasonographic examination revealed a normal fetus with a huge, multicystic placenta. Chromosomal evaluation by amniocentesis revealed a normal female karyotype (46,XX), and serial biometric measurement of the fetus showed normal growth during pregnancy. There were no obstetric complications until the 32nd gestational week when preterm rupture of the membranes occurred. The electronic fetal heart beat tracing showed a repeated sinusoid pattern and late deceleration after admission. The patient underwent emergency Caesarean section and delivered a 1551-g, anaemic female baby with an Apgar score of 1, 4 and 6 at 1, 5 and 10 min, respectively. The baby recovered within 2 weeks after respiratory support and transfusion of packed red blood cells. Although anaemia is one of the risk factors that jeopardize the fetus in the case of partial molar pregnancy, termination is not indicated when the fetus is normal and no complications have occurred.

Key words: ß-human chorionic gonadotrophin/electronic fetal monitoring/fetal anaemia/partial molar pregnancy/ultrasound


    Introduction
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 Abstract
 Introduction
 Case report
 Discussion
 References
 
Excluding cases of multiple conception with molar pregnancy and coexisting fetuses, partial molar pregnancy in which a live fetus is carried to term is very rare. Partial hydatidiform moles coexisting with fetal tissue or an anomalous fetus generally result from dispermy and have a triploid karyotype in the majority of cases (Szulman and Surti, 1978aGo,bGo; Ohama et al., 1986Go). Fetuses with triploidy cannot survive after birth because of multiple malformations and severe intrauterine fetal growth retardation. Several factors may affect the outcome of the fetus in cases of partial molar pregnancy, such as the karyotype of the fetus, the size of the abnormal molar placenta, the speed of molar degeneration, and the occurrence of fetal anaemia or other obstetric complications (Jones and Lauersen, 1975Go; Teng and Ballon, 1984Go; Crooij et al., 1985Go; Sarno et al., 1993Go). Survival of a normal live fetus coexisting with the partial mole, unlike the classical complete mole and partial triploid mole, is extremely rare and may represent another disease (Feinberg et al., 1988Go; Deaton et al., 1989Go; Sarno et al., 1993Go).


    Case report
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 Abstract
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 Case report
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The patient was a 30-year-old, Taiwanese nulliparous woman. She received routine obstetric evaluation at 16 weeks gestation. No family history of genetic abnormality or difficult pregnancy was identified. Both serum ß-human chorionic gonadotrophin (ß-HCG) and {alpha}-fetoprotein (AFP) were elevated in a prenatal Down's syndrome screening programme. The ß-HCG titre was 167 596 mIU/ml, 6.68 multiples of the median (MoM) and the titre of AFP was 1846 ng/ml, 34.2 MoM at the 16th gestational week.

Ultrasonographic examination at 18th weeks revealed a live fetus with a huge hydropic placenta that appeared to have multiple cysts and occupied most of the uterine cavity. The features were consistent with molar changes and the fetus was found to have a normal brain, heart, and other major structures. The umbilical cord was connected to the area near to the honeycomb-like placenta (Figure 1Go). Pericardial effusion was the only finding in consultative fetal echocardiography, but it disappeared 2 weeks later. A chest X-ray showed no evidence of metastases and thyroid and liver function tests were normal. Genetic amniocentesis disclosed a normal female karyotype (46,XX). Partial molar pregnancy was diagnosed.



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Figure 1. The umbilical cord (marked by +....+) was noted connecting to the partial molar placenta (right upper) at 18 weeks gestation. Scale bar 5 cm.

 
Even though no other significant abnormalities were noted during serial examinations, the risk of subsequent fetal complications and malignant transformation of this molar pregnancy were explained to the patient and her family. The patient elected to continue her pregnancy and received regular antenatal care at our outpatient clinic. During that period, evaluation revealed no evidence of hypertension, proteinuria, vaginal bleeding, or any other obstetric complication. Maternal serum titres of ß-HCG were found to have decreased to 66 073 mIU/ml, 66 587 mIU/ml, and 68 569 mIU/ml at 21, 25 and 29 weeks gestation respectively. The serial biometrics of the fetus were measured every 2 weeks from weeks 18 to 32 and showed a normal growth pattern corresponding to the gestational age. By ultrasound, the partial molar placenta did not change very much, except for a large cistern formation near its margin. The biophysical profile during pregnancy was evaluated biweekly and non-stress test was performed weekly after 26 gestational weeks.

The clinical course was smooth until the 32nd gestational week, when the patient was admitted to the labour room due to premature rupture of the membranes. Admission laboratory findings of the patient included white blood count 7.8x103/mm3, haemoglobin 10.3 g/dl, haematocrit 30.4%, mean cell volume 90.5 µm3, and platelet count 152x104/mm3. The serum titre of ß-HCG was 37 222 mIU/ml. Ultrasonography showed borderline intrauterine growth retardation (12 percentile) with decreased amniotic fluid index (as 3.3 cm). Neither ascites nor pericardial effusion was found. After admission, the fetal heart beat tracing revealed sinus tachycardia with decreasing beat-to-beat variability and occasional late deceleration, which changed to a sinusoid pattern 6 h later.

Because of acute fetal distress and suspicion of anaemia, a preterm female baby with body weight 1551 g was delivered by Caesarean section. The Apgar scores were 1 at 1 min, 4 at 5 min, and 6 at 10 min with intubation. The baby looked very pale and flaccid and was transferred to the neonatal ICU after resuscitation. The bulky area of the placenta appeared to be filled with a diffuse cluster of vesicles. The normal area of the placenta appeared to have been invaded and merged by the hydatidiform mole over the central area of the placenta, with resulting multiple haemorrhage (Figure 2Go).



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Figure 2. Gross picture of the placenta showing multiple haemorrhage and a diffuse cluster of molar vesicles. Scale bar 10 cm.

 
Postnatal laboratory findings included white blood count 20.8x103/mm3, haemoglobin 4.2 g/dl, haematocrit 14.3%, and platelet count 71.5x104/mm3. Direct Coombs' test of the newborn and Kleihauer–Betke test of the mother were both negative. Blood gas analysis of the newborn showed pH 7.21, paO2 72 mmHg, paCO2 43.5 mmHg, HCO3 17.6 mmol/l. Chest X-ray of the newborn revealed grade II to III respiratory distress syndrome. Sonographic examination of the neonatal brain, abdomen, kidneys, and heart found no abnormalities except for mild non-specific hepatomegaly. During the next 2 weeks, the newborn recovered completely after red blood cell transfusion and respiratory support.

Pathological study of the placenta showed an immature organ with an admixture of normal and hydropic villi with dilated cisterns and scalloped borders (Figure 3Go). The trophoblastic proliferation was focal without atypical change. The serum titre of ß-HCG of the mother decreased to undetectable levels 1 month after delivery without any chemotherapy. She was doing well and had no evidence of recurrence after 18 months of follow-up. The female baby was normal without any complications at 18 months follow-up.



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Figure 3. Microscopic picture of the placenta showing an admixture of normal villi (arrowhead) and molar villi (arrow) with dilated cistern formation (haematoxylin and eosin, original magnification x64).

 

    Discussion
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 Case report
 Discussion
 References
 
Hydatidiform mole with coexistent normal fetus is not necessarily considered as a partial mole. Cases of such association can be classified into three types (Figure 4Go). The first is a twin pregnancy with one normal fetus (normal placenta) and another complete mole (Sauerbrei et al., 1980Go; Changchien et al., 1994Go; Chen, 1997Go); the second is a twin pregnancy with one normal fetus (normal placenta) and another partial mole (Nwosu et al., 1995Go; Nugent et al., 1996Go); and the third is a singleton normal fetus with partial molar placenta (Jones and Lauersen, 1975Go; Sauerbrei et al., 1980Go; Crooij et al., 1985Go; Sarno et al., 1993Go) as in our patient.



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Figure 4. Illustration of three categories of hydatidiform mole with coexistent normal fetus and two types of partial molar placenta.

 
In cases of a singleton normal fetus with partial molar placenta, the fetus must have normal karyotype to survive in utero, although its placenta can have some variation, from diploidy of the amnion to triploidy of the chorionic villi (Sarno et al., 1993Go). From this clinical perspective, there are two different types of gross pathology in the placenta: the focal and diffuse partial degeneration (Jones and Lauersen, 1975Go; Deaton et al., 1989Go; Vejerslev, 1991Go). The former represents separation of the normal and abnormal molar degeneration in a single placenta with a varied ratio. The difference between a focal partial molar degeneration and twin pregnancy with complete mole cannot be firmly established by ultrasound per se because they both present with two distinct regions of the placenta. On the contrary, ultrasonographic detection of diffuse partial degeneration is much easier because of the readily identifiable characteristic picture as in the case of our patient. Our prenatal diagnosis of diffuse partial mole depended upon the ultrasonographic finding of molar invasion into the normal placenta without clear margin. The prognosis is grave because of the relatively smaller region of functional placenta. Only one case of diffuse partial molar pregnancy in which the infant survived has been reported (Sarno et al., 1993Go).

To date, eight cases of partial mole coexisting with the fetus with normal karyotype after 15 gestational weeks have been reported (Table 1Go), but only two of the infants survived. Most of the cases of partial molar pregnancy diagnosed early in the gestation have been terminated (Szulman and Surti, 1978aGo; Teng and Ballon, 1984Go; Deaton et al., 1989Go), with or without medical complications. Partial molar pregnancy with fetal survival depends upon several factors: (i) normal karyotype of the fetus (Sarno et al., 1993Go); (ii) smaller molar placenta compared to normal placenta (Jones, and Lauersen, 1975Go; Deaton et al., 1989Go); (iii) the onset of the molar degeneration and its speed of degeneration (Jones and Lauersen, 1975Go; Sarno et al., 1993Go); (iv) absence of anaemia occurring in the fetus (Crooij et al., 1985Go); and (v) absence of maternal complications such as pre-eclampsia, thyrotoxicosis, and vaginal bleeding interrupting the pregnancy (Teng and Ballon, 1984Go).


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Table I. Clinical features of partial mole and coexisting fetus with normal karyotype
 
Recent advances in prenatal diagnosis by ultrasound may allow partial and complete molar placenta coexisting with the fetus to be distinguished in many cases. In our patient, crucial information about the differential diagnosis was obtained from the site of umbilical cord insertion. If this area is near to the abnormal honeycomb-like placenta, as in the case of our patient, partial mole with coexistent fetus is the diagnosis. The distinction between normal and abnormal placenta on ultrasound might occur in either partial mole with focal degeneration or twin pregnancy with one fetus and another partial or complete mole (Deaton et al., 1989Go; Chen, 1997Go). In these situations, a chromosome banding study might be performed to exclude a complete mole, in which only paternal markers are present. A more reliable method of determining paternal markers, however, would be by molecular genetic studies.

The coexistence of a partial mole with a normal live fetus is rare. The present case was followed sonographically from the 18th gestational week until birth. Ultrasonographic examinations before and after delivery found no signs of congestive heart failure such as fetal ascites, pleural effusion or skin oedema nor any other evidence of chronic fetal blood loss throughout the pregnancy. Postnatal echocardiography revealed no evidence of major congenital cardiac malformation, cardiomegaly or pericardial effusion. The occurrence of acute blood loss in association with partial molar pregnancy could explain why fetal distress developed in this case.

Fetal anaemia caused by fetomaternal transfusion in a case of partial mole has been previously reported before (Crooij et al., 1985Go). Although the neonatal anaemia was effectively treated by exchange transfusion, the infant died from respiratory distress syndrome 67 days after birth. In our patient, severe fetal anaemia was probably due to fetal bleeding into the abnormal hydatidiform molar placenta. The haemorrhage might have been triggered by preterm rupture of the fetal membranes before admission. Evidence for this possibility was seen as multiple haemorrhage over the maternal side of the placenta specimen. However, we could not rule out the possibility of abruptio placentae because of fetal anaemia, placental appearance, and findings of fetal monitoring. Fetal anaemia resulting from the placental site haemorrhage could result in intrauterine fetal death. In our patient, ominous signs of fetal distress including fetal tachycardia, sinusoid pattern, and late deceleration were shown by fetal electronic monitoring. Under these conditions, if the haemodynamic status changed rapidly, the anaemic fetus would be at high risk of intrauterine fetal death. This is the primary reason that survival of a fetus with partial mole is so rare.

Although Feinberg et al. (Feinberg et al., 1988Go) suggested that an elevated AFP concentration, as in our patient, could represent a diagnostic marker for partial hydatidiform mole, a case reported by Sarno et al. (Sarno et al., 1993Go) did not show any elevation of maternal serum AFP. The role of high AFP in cases of partial hydatidiform mole is not clear and needs further investigation.

Szulman and Surti (1982) reviewed 86 cases of partial hydatidiform mole and 115 cases of complete mole, and showed that the total incidence of residual disease was lower in the former (4.0%) than the latter (10.7%). However, Berkowitz et al. reported that more patients (9.9%) had developed persistent gestational trophoblastic disease (Berkowitz et al., 1985Go). Our patient did not show any persistent trophoblastic disease after birth and her serum ß-HCG titre returned to normal within 4 weeks. Termination of the partial molar pregnancy is sometimes necessary because of pre-eclampsia (2.5–6% of cases) or heavy vaginal bleeding (8% of cases) (Berkowitz et al., 1985Go; Vejerslev, 1991Go). Although the partial mole displays most of the pathological and clinical features of the complete mole, it seems to represent a milder version of the latter, as seen in placental morphology, ß-HCG titres, and the incidence of pre-eclampsia, thyrotoxicosis, hyperemesis, and haemorrhage. For this reason we do not think it is necessary to terminate partial molar pregnancy when the fetus is normal and there are no clinical complications.

It is very interesting that all of the reported cases of non-triploidy partial mole have had female karyotype (46,XX) except for one case (Table IGo) reported by Teng and Ballon (Teng and Ballon, 1984Go). Deaton et al. (1989) questioned the validity of the study of Teng and Ballon because they did not perform chromosome banding studies to exclude the possibility of a complete mole with a twin gestation. The occurrence of a normal female baby in partial mole may represent a different manifestation from the classical complete mole and partial triploid mole (Feinberg et al., 1988Go; Deaton et al., 1989Go; Sarno et al., 1993Go).

In conclusion, pregnancy with a normal live fetus and a partial molar placenta is extremely rare because of maternal and fetal complications. These complications include pre-eclampsia, hyperthyroidism, heavy vaginal bleeding, persistent gestational trophoblastic disease, preterm labour, and late abortion. A severely anaemic fetus caused by the abnormal placenta, as we reported, represents another clinical manifestation.


    Notes
 
3 To whom correspondence should be addressed at: Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, 199 Tun Hwa North Road, Taipei 105 Taiwan, Republic of China Back


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 Abstract
 Introduction
 Case report
 Discussion
 References
 
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Submitted on June 26, 1998; accepted on December 10, 1998.