CMV infection: when should medical termination of pregnancy be discussed?

OBJECTIVES: To determine in which circumstances termination of pregnancy (TOP) could be proposed in case of CMV infection. PATIENTS AND METHODS: An inquiry was conducted concerning the practice of doctors working in French foetal medicine units in case of CMV infection. The question asked was: "What is your attitude if confronted to a CMV seroconversion at 23 weeks of amenorrhoea with positive PCR at 28 WA, and normal MRI and ultrasound scan at third trimester?" RESULTS: Thirty-five obstetricians answered. Forty-nine percent do not perform foetal blood sampling (FBS). Among them 1/17 would accept TOP. Fifty-one percent do perform FBS. In this group, 33% would accept TOP in case of negative FBS and 83% if FBS shows foetal infection. DISCUSSION AND CONCLUSION: Techniques available for diagnosis and prognosis of foetal infections are based on PCR on amniotic fluid, ultrasound, MRI and FBS. To date correlation of those tests with foetal outcome has not been fully validated. TOP could therefore be an option in 2 circumstances: when signs of certain severe foetal disease with positive PCR and ultrasound abnormalities; on statistical arguments: if positive PCR, and normal ultrasound, the risk of handicap is approximately 10%, the severity of the handicap being impossible to predict. In this last hypothesis, it is tempting to use additional arguments such as FBS even if the interpretation of the results of this test has not been scientifically validated. Such cases with positive PCR and normal ultrasound in which inconsistent decisions are made are likely to be more frequent because of routine serologic screening policy.     

Cytomegalovirus (CMV) and rubella virus infection during pregnancy. A study of CMV and rubella virus antibodies in 2014 pregnant women and follow-up studies of infants at risk for intrauterine CMV infections

Two blood samples, one in the first and one in the third trimester, were collected from 2014 pregnant women. Serological tests for CMV and rubella antibodies were performed in the paired samples. Seroconversion by the CF test for CMV antibodies was demonstrated in 15 women. However, seroconversion also by the IF test was found in only one of these. A rise in titer during pregnancy by the CF test was found in 16 woman. None of these specimens contained specific IgM. High CMV-CF antibody titer (greater than 128) in the first serum sample was found in 28 women, but none of the sera contained specific IgM. It is concluded that no single serological test can serve at present as a screening test for the diagnosis of CMV infection during pregnancy. In children thought to be at risk contracting congenital CMV infection, no case with CNS malfunction that could be attributed to a congenital CMV infection could be demonstrated at the age of 7-8 years. One case of seroconversion in the examination for rubella antibodies was found. The infant of this mother showed no clinical signs of rubella infection.     

Triploidy in a twin pregnancy: small placenta volume as an early sonographical marker

INTRODUCTION: We report a case of a twin pregnancy with triploidy of maternal phenotype of one foetus and no chromosomal anomaly of the other twin and the role of sonographical placental volumetry. CASE: At 12 weeks of gestation, a dichorionic twin pregnancy discordant in growth is diagnosed. 3D ultrasound reveals a distinctly small placental volume of foetus II. Amniocentesis at 16 weeks discloses triploidy of this foetus. Sonography reveals asymmetrical foetal growth retardation, a severe heart defect and bilateral cleft lip and palate, typical findings in triploidy. Selective feticide at week 20+3 is followed by pre-term birth of foetus I at 27 weeks. CONCLUSION: Small placental volume in addition to growth restriction of one foetus early in the course of a twin pregnancy could be an important early marker influencing the decision for chorionic villous sampling at 12 weeks instead of amniocentesis at 16 weeks and it could lead to an earlier selective pregnancy termination of a triploid twin. This would lower the risk of pre-term birth and enable a better outcome for the remaining healthy foetus.     

Le syndrome de réponse inflammatoire fœtale : définition, causes et conséquences

Fetal inflammatory response syndrome (FIRS) is caused by stimulation of the foetal immune system and biosynthesis of pro-inflammatory cytokines in the human foetus following intra uterine infection and/or premature membrane rupture. Several diagnostic features characterise FIRS during foetal life or at birth, including elevated levels of interleukin-6 in the cord blood, histological funiculitis or small foetal thymus size measured by ultrasound. A relationship between neonatal morbidity and foetal inflammation has been demonstrated by the increased concentration of IL-6 in cord blood or amniotic fluid in children who develop periventricular leukomalacia, bronchopulmonary dysplasia or cerebral palsy. Preventing adverse neonatal outcome associated with FIRS is a real challenge for neonatology. In at risk situations, such as premature rupture of membranes, maternal glucocorticoids, antibiotic therapy and the obstetric point of view (whether to continue with the pregnancy or extract the foetus) must be discussed.     

Focal sonographic periventricular pattern associated with mild ventriculomegaly in foetal cytomegalic infection revealing cytomegalic encephalitis in the third trimester of pregnancy

OBJECTIVES: To report focal sonographic periventricular pattern related to residual germinal matrix lesions in foetal cytomegalic infection in association with mild ventriculomegaly seen during the third trimester of pregnancy correlating with neuropathological findings of encephalitis. METHODS: We reviewed prenatal cerebral sonographic examination performed in three patients, during the third trimester of pregnancy, looking for either late 'isolated' ventriculomegaly (n = 2) or sonographic follow-up of cerebral structures following a known primary CMV infection in the early stage of pregnancy (n = 1). In cases of isolated ventriculomegaly, serological examination identified prenatal CMV infection. Magnetic resonance imaging (MRI) was performed in all cases. Imaging findings were compared with those following neuropathological examination. RESULTS: In all cases, ultrasound examination revealed an abnormal focal symmetrical bilateral periventricular pattern on the mid-lateral border of the lateral ventricles, including a mainly hyperechogenic lesion containing a few microcysts (case 1), a mixture of echogenic tissue and cysts (case 2) and mainly cystic areas (case 3). No alteration of cephalic biometry was noted. Neuropathological examination correlated these abnormal areas with lesions of the residual germinal matrix including inflammation and necrosis, but revealed also an extensive inflammatory process of the whole foetal brain. CONCLUSIONS: This focal sonographic periventricular pattern associated with mild ventriculomegaly without any abnormalities of the cerebral and cerebellar organogenesis nor cephalic biometry alteration in the third trimester of pregnancy should be considered as a marker of encephalitis following CMV infection of the foetal brain.     

Twin pregnancy and congenital cytomegalovirus: Case report and review

Primary cytomegalovirus (CMV) infection during pregnancy is the leading infectious cause of congenital neurological disabilities. Diagnosis of maternal primary CMV infection and fetal compromise can be difficult, as well as the fact that most infected child are asymptomatic at birth, which makes binomial CMV and pregnancy challenging. The treatment of pregnant women with CMV hyperimmunoglobulin (CMV-HIG) has shown promising results. However, as far as we know, no randomized trials of immunoglobulin therapy of CMV-infected fetuses are ongoing. We describe CMV-HIG administration for twin pregnancy as maternal and fetal infection early in gestation. The epidemiology, clinical manifestations, prevention strategies and treatment of CMV infections are reviewed.     

Characteristics and serology of pregnant women with cytomegalovirus immunoglobulin G seroconversion during pregnancy in Japan

ObjectiveInvestigate the characteristics and serology of pregnant women with cytomegalovirus (CMV) immunoglobulin (Ig)G seroconversion during pregnancy to understand the risk factors associated with primary CMV infection and the occurrence of fetal congenital CMV infection.Materials and methodsWe retrospectively studied 3202 pregnant women who were CMV IgG-negative in early pregnancy and were retested for IgG in late pregnancy. Characteristics were compared between participants with and without IgG seroconversion, and serological parameters were compared between participants with and without fetal congenital CMV infection.ResultsTwenty-six participants showed CMV IgG seroconversion and fifteen showed fetal congenital CMV infection. Seroconversion rates were significantly higher in teens (5.0%) than in older women (20s: 0.8%; 30s and over: 0.6%) (p < 0.001). Titers of CMV IgM at IgG seroconversion were higher in women without (median 8.66) than with (median 6.54) congenital infection (p = 0.045). The congenital infection rate was high when IgM titers at IgG seroconversion were low (47.1% with 4.00–12.00 titers and 100% with 1.21–3.99 IgM titers) (p = 0.048).ConclusionsNulliparous pregnant teenagers have a high risk of CMV IgG seroconversion and the CMV IgM titer at IgG seroconversion may help predict the occurrence of fetal congenital CMV infection.     

Pheochromocytoma and pregnancy. Case report

The management of a pheochromocytoma during pregnancy is uncommon and is at high risk for both mother and foetus. We report a case of a patient whose first pregnancy was complicated by foetal demise in a context suggestive of preeclampsia. She was diagnosed with pheochromocytoma as she was beginning a second pregnancy. A laparoscopic adrenalectomy was performed in the first trimester of pregnancy, and maternal and neonatal outcome were favourable. This case illustrates the difficulty of diagnosing pheochromocytoma in pregnancy, and the benefits of laparoscopic treatment in the first trimester.     

Intraventricular haemorrhage in a fetus with cerebral cytomegalovirus infection

Cytomegalovirus (CMV) is the leading infectious cause of prenatal neurological damage, which is particularly severe when primary maternal infection occurs during the first 16 weeks of gestation, at the time of organ development and neuronal migration. Vascular involvement has been suggested to be among the possible pathogenic mechanisms of virus-induced pathology, in addition to direct viral effects. We report on a fetus with cerebral CMV infection, which had intraventricular haemorrhage, together with oligohydramnios and hyperechogenic bowel, following maternal primary CMV infection.     

A 2-year study on cytomegalovirus infection during pregnancy in a French hospital

Objectives  To evaluate the proportion of pregnant women agreeing to cytomegalovirus (CMV) serologic screening. To collect data on CMV infection during pregnancy.
Design  Prospective study.
Setting  During two years, all pregnant women were informed on CMV infection. If the patient agreed, serological testing was performed around 12 weeks of gestation (WG) and, if negative, redone around 36 WG.
Population  Four thousand two hundred and eighty-seven pregnant women followed from 12 weeks to delivery.
Methods  If the first CMV serologic test was negative, detailed hygiene information was given to the parents. Diagnosis of primary infection was based on the detection of CMV-G, CMV-M and low CMV-G avidity index. When maternal infection was confirmed, diagnosis of CMV congenital infection was done in the newborns by urine culture within the three days following birth. Crude infection-rate data consisted of the number of CMV infection cases and person-time units for both exposed to hygiene CMV information (12 to 36 WG) and unexposed pregnant women (first 12 WG).
Main outcome measures  Rate of CMV seropositive and seronegative women. Rate of women agreeing for screening. Rate of primary infection. Rate of seroconversion. Number of CMV-infected newborns.
Results  Among the 4287 women followed, 3792 were either seronegative or with an unknown immune status. 96.7% out of them agreed for screening. 53.2% were initially CMV-specific IgG negative. Primary infection was detected in nine women between 0 and 12 WG (0.46%) and seroconversion was diagnosed in five women between 12 and 36 WG (0.26%) (mid P  = 0.02, 95% CI [1.07–13.6]).
Conclusions  If clear information on CMV infection during pregnancy is given, patients frequently agree to screening. The rate of seroconversion after information, observed in this study, is low after counselling.     

Face presentation: retrospective study of 32 cases at term

OBJECTIVE: To determine the etiologic factors, circumstances of diagnosis, obstetrical management and complications of face presentation and to value the maternal and foetal prognosis of this presentation. PATIENTS AND METHODS: Thirty-two cases of face presentation have been observed in the maternity wards of Reims and Troyes over the last 12 years. RESULTS: The incidence of face presentation was 0.7 per 1000 deliveries. Spontaneous vaginal delivery occurred with mento-anterior presentation 73% of the time and caesarean section was performed in 100% of mento-posterior presentation. There was no increasing rate of foetal or maternal mortality and morbidity with vaginal delivery. DISCUSSION AND CONCLUSION: Face presentation is an unusual complication of pregnancy with obstetric factors that predispose the foetus to face presentation. The low foetal and maternal mortality and morbidity substantiate the effectiveness of conservative management in face presentation.     

Maternal and foetal consequences of dengue fever during pregnancy

Objective

The aim of the study was to assess the maternal and foetal consequences of dengue fever infection during pregnancy.

Study design

A retrospective study was carried out from 1 January 1992 to 10 September 2006 on 53 pregnant women infected with the dengue virus during pregnancy. The women were patients of the obstetrics and gynaecology department of Saint Laurent du Maroni hospital. A dengue infection was confirmed either by the presence of specific IgMs or by isolation of the virus (PCR or culture). The data collected related to obstetric and foetal consequences both during pregnancy and at birth, as well as the effect on the newborn.The risk of maternal–foetal transmission was assessed from 20 samples of blood taken from the umbilical cord at birth.

Results

The principal maternal consequences were: premature labour (41%), premature birth (9.6%), haemorrhage during labour (9.3%: 5 cases) and retroplacental haematoma (1.9%: 1 case).Foetal consequences were: prematurity (20%), foetal death in utero (3.8%: 2 cases), late miscarriage (3.8%: 2 cases), acute foetal distress during labour (7.5%: 4 cases), maternal–foetal transmission (5.6%: 3 cases) and neonatal death (1.9%: 1 case).

Conclusions

Maternal infection with the dengue virus during pregnancy represents a real risk of premature birth.There is also a risk of haemorrhage both for the mother and the baby when infection occurs near term.     

Red-cell alloimmunization

Morbidity and mortality due to Rhesus antibodies in pregnant women's serum have steadily declined because of various factors which include, implementation of routine antenatal anti-D prophylaxis and development of non-invasive investigations for monitoring Rhesus affected pregnancies. Because at present this condition is so rare, any case of red-cell alloimmunization should be managed in liaison with a specialist in foetal medicine. Unlike the first immunized pregnancy, maternal antibody titres are not predictive of foetal risk in any subsequent pregnancies. Serial peak middle cerebral artery velocities using Doppler can be used in these pregnancies to detect foetal anaemia. Foetal blood type can now be determined by new techniques to detect free foetal DNA in maternal plasma. In selected cases depending on the gestational age of foetus intrauterine transfusion is necessary through ultrasound directed puncture of the umbilical cord with the direct intravascular infusion of red blood cells. Perinatal survival rates of more than 90% have been reported.     

Neonatal screening for congenital cytomegalovirus infections.

We evaluated a screening program for the detection of congenital cytomegalovirus in 3075 unselected pregnant women. From each live-born child urine for CMV culture was collected within 7 days after birth. Each fetus expelled after a spontaneous second trimester abortion and each stillborn infant were also evaluated for a possible congenital CMV infection. For each congenital infection stored maternal sera were analysed to determine whether maternal infection was primary or recurrent. Fifteen out of the 3075 pregnancies studied resulted in a congenitally infected infant (0.49%). Nine maternal CMV infections were primary infections; five were recurrent infections, and in one case the type of infection could not be determined. Three congenital infections resulted in severe sequelae, leading to the termination of pregnancy in two instances and to neonatal death in one case. One of these severe fetal infections was due to a recurrent maternal infection. Follow-up of the other 12 neonates demonstrated hearing disorders in two children. One was born after a primary maternal infection and one after a recurrent maternal infection. We conclude that congenital CMV infections occurs in 0.49% of all pregnancies in the population studied. Twenty percent of the congenitally infected infants present severe sequelae at birth or during pregnancy, and an additional 17% have audiological deficits at 1 year of age. Severe sequelae may occur after both primary and recurrent maternal CMV infection.     

Pregnancy in mother with Glanzmann's thrombasthenia and isoantibody against GPIIb–IIIa: Is there a foetal risk?

Glanzmann's thrombasthenia (GT) is a rare autosomal recessive platelet disorder caused by qualitative or quantitative abnormalities of a platelet glycoprotein complex (GPIIb-IIIa) leading to excessive bleeding. Platelet transfusions are the first-line therapy for severe or persistent bleeding and surgery. Isoantibody against GPIIb-IIIa complexes present on normal platelets can be observed in Glanzmann's thrombasthenia type I patients after platelet transfusion possibly leading to platelet transfusion refractoriness. Pregnancy in Glanzmann's thrombasthenia type I women is rare, and severe bleeding can be observed in the peripartum or late postpartum period. Moreover, pregnancy can contribute to the maternal isoimmunization by the passage of the foetal cells into the maternal circulation. The transplacental passage of the maternal isoantibodies can induce moderate to severe foetal thrombocytopenia. We discuss here the case of in utero death at 31 weeks of gestation due to intracranial haemorrhage in an immunized mother and review the literature. Presence of isoantibody prior to gestation or detected during the index pregnancy must be taken into account in evaluating risk for the mother and the foetus.     

Congenital cytomegalovirus infection following primary maternal infection in the third trimester

Objective  To determine the effect of primary cytomegalovirus (CMV) infection in the third trimester on fetal outcome.
Design  Observational study.
Setting  Four perinatal departments in tertiary hospitals in Israel.
Population  Twenty-eight women with primary CMV infection acquired after 25 weeks of gestation.
Methods  Prenatal evaluation included amniocentesis and ultrasonographic examinations. Maternal infection was determined from seroconversion and presence of low avidity anti-CMV immunoglobulin G after 25 weeks of gestation. Fetal CMV infection was diagnosed from CMV isolated or CMV DNA amplified from the amniotic fluid. Neonatal infection was established from CMV presence in their urine or anti-CMV IgM was in their peripheral blood immediately after birth. All liveborn neonates underwent cerebral ultrasonography, hearing assessment, and psychomotor development evaluation. Infected neonates were followed up for a median of 36 months (range 6–36 months).
Main outcome measures  Intrauterine CMV infection and neonatal CMV disease throughout follow up.
Results  Vertical transmission of CMV was documented in 21 (75%) of the 28 pregnancies. None of the 20 live infected newborn had symptomatic congenital infection. One pregnancy was terminated at 34 weeks following evidence of prenatal infection. Most of the patients (75%) had CMV serology test due to clinical signs of CMV disease.
Conclusions  Although CMV infection during the third trimester of pregnancy is highly transmissible, sequelae were not found among infected offspring.     

Sepsis due to Clostridium perfringens after pregnancy termination with feticide by cordocentesis: a case report

We report a case of sepsis due to Clostridium perfringens after termination of pregnancy at 22 weeks with feticide by cordocentesis. Three weeks earlier, the 41-year-old patient had undergone an amniocentesis and a full trisomy 13 karyotype had been discovered. Feticide was performed by injection of thiopental and potassium chloride after percutaneous umbilical foetal blood sampling through the same needle. The patient delivered vaginally with signs of chorioamnionitis and septicaemia. She recovered under broad-spectrum antibiotherapy. C. perfringens was present in maternal blood cultures, placental smears and foetal organs. We discuss the possible mechanisms of infection by C. perfringens, including inoculation of intestinal germs.     

CMV Infection and Pregnancy

Cytomegalovirus (CMV) occurs in 0.2?% to 2.2?% of all live births and is the most common cause of intrauterine infection and the leading infectious cause of sensorineural hearing loss and mental retardation. This article reviews literature that relate to the pathogenesis, diagnosis, and treatment of this disease for pregnant women and their fetus. Primary maternal CMV infection during pregnancy has a much higher rate of mother-to-fetus transmission and causes symptoms at birth and long-term disability than nonprimary infection. In addition, some research has shown that children with congenital CMV infection following first-trimester maternal infection are more likely to have severe sequelae. The prenatal diagnosis of fetal CMV infection includes serological testing (IgM detection and IgG avidity assay), amniocentesis, and ultrasound examination. The combination of the presence of CMV IgM antibodies and low CMV IgG avidity, along with maternal or fetal symptoms is used for the diagnosis of a primary maternal infection. Amniocentesis should be complemented until approximately 20-21?weeks of gestation to increase the sensitivity. Because ultrasound abnormalities are only found in less than 25?% of infected fetuses, ultrasound is as a relatively poor predictor of symptomatic congenital infection. CMV hyperimmunoglobulin also may be considered when the pregnant women are confirmed as primary CMV infection with low IgG avidity and amniotic fluid is found to contain CMV or CMV DNA. There is no consensus on the benefit of prenatal administration of ganciclovir into the umbilical vein.     

Specific follow-up for pregnant patients with a thyroid dysfunction

Association between thyroidian disease and pregnancy is a frequent event. Thyroidian hormones are mandatory for foetal development especially at the level of brain structures. Any shortage of thyroidian hormone can severely and irreversibly alter neurological development. On the other hand it is also clear that an excess of thyroidian hormone can jeopardize the embryo then the foetus. In case of maternal hyperthyroidism, strict guidelines relying mainly on foetal thyroid monitoring echographic scanning will allow in most cases the delivery of a healthy euthyroid newborn. Hypothyroidia, providing an adequate substitution, has no significant impact on pregnancy. Biological monitoring is the key of monitoring. Iodine deficiency is a matter of concern when considering neurodevelopmental outcome, however it is still an unsolved issue in France. A multidisciplinary team will sometimes be necessary for taking care of pregnant patients with active Graves' disease.     

Detection of a novel dystrophin gene mutation through carrier analysis performed during prenatal diagnosis in a case with intragenic recombination

OBJECTIVES: To report a multi-technical approach to Duchenne muscular dystrophy (DMD) mutation testing through carrier analysis, in the prenatal diagnosis of a male foetus without a known mutation segregating in the family and with inconclusive results of linkage analysis. METHODS: Haplotype analysis with the DMD region markers for assigning the carrier status of the mother and for prenatal diagnosis of foetal DNA; semiquantitative multiplex analysis of maternal and foetal DNA for the promoter and for 34 exons of the DMD gene; sequencing analysis of the maternal and foetal DNA for confirmation of the results. RESULTS: Because of an intragenic recombination of the DMD gene in foetal DNA, haplotype analysis gave inconclusive results. Semiquantitative PCR analysis displayed a pattern compatible with a heterozygous exon 60 mutation in the mother's DNA, while foetal DNA showed a normal migration pattern. Sequencing analysis confirmed the presence of a novel 7 base-pair deletion in exon 60 of the DMD gene in the mother and excluded the deletion in the foetus. CONCLUSION: Semiquantitative PCR results allowed the DMD mutation detection in the mother and the exclusion in the foetus, showing its crucial importance in prenatal diagnosis in those cases where linkage analysis is not conclusive.