Campylobacter coli infection causing second trimester intrauterine growth restriction (IUGR): a case report and review of the literature

Campylobacter is a gram-negative, microaerophilic, curved rod and a normal resident of the gastrointestinal flora and may be the cause of disease in animals. Transmission to humans occurs by ingestion of contaminated food or by direct contact with infected animals. In the past few decades, an increasing number of reports have implicated the presence of this organism in human abortions as well. An infectious mechanism due to primary placental inflammatory damage followed by secondary damage to the fetus following placental insufficiency and ischemia was suggested. The most common species of Campylobacter are Campylobacter jejuni and Campylobacter coli, which are classically associated with enteritis in humans. We present a rare case of mid-gestation intrauterine growth restriction (IUGR) associated with maternal bacteremia caused by C. coli infection. Our literature review focuses on Campylobacter infections occurring in the second and third trimesters of pregnancy. In all cases, mild maternal symptoms consisting of fever and weakness were presented. However, associated adverse fetal outcome, including abortions, IUGR or preterm labor may occur more frequently than anticipated. Our report strengthens the importance of awareness to this finding and focuses the need to consume properly cooked meat during pregnancy. © 2015 John Wiley & Sons, Ltd.     

Confined placental mosaicism,IUGR, and adverse pregnancy outcome: A controlled retrospective U.K. collaborative survey

In a retrospective collaborative study involving 21 U.K. laboratories and 11775 CVS prenatal diagnostic procedures, a total of 73 cases of confined placental mosaicism (CPM) were identified among the 8004 first-trimester referrals because of advanced maternal age, a previous child with a numerical chromosome abnormality, or a family history of the same. Data were collected on subsequent cytogenetic follow-up and pregnancy outcome for each case and a referral matched control. Comparison with the control population failed to demonstrate a marked increase in adverse pregnancy outcome in the CPM group, but a significant increase in both low and high birth weight infants was recorded. In a parallel study, 7 out of 108 cases, referred for prenatal diagnosis because of ultrasound detection of isolated intrauterine growth retardation (IUGR) in the second or third trimester, were shown to have a chromosome abnormality restricted to the extraembryonic tissues. These included cases of CPM involving trisomy 9 and del(13)(q13), neither of which has previously been reported in association with IUGR.     

Trisomy 16 confined to the placenta

Two cases with trisomy 16 confined to the placenta are presented. Prenatal diagnosis was indicated because of fetal growth retardation. In case 1, a phenotypically normal but small-for-date boy was born. In case 2, the fetus turned out to be triploid on cordocentesis. In both instances the trisomy 16 was recovered from the placenta. Recovery indicates that the abnormality was present in the placenta during the time of fetal growth retardation, which supports an aetiological relationship. Strict appliance of the current models cannot readily explain the observed discrepancies. In case 2, a chimeric placenta as a result of a vanishing twin is assumed. Cases of placental trisomy 16 published after 1988 are reviewed. It is concluded that confined placental trisomy 16 can cause intrauterine growth retardation if present in both the direct preparation and the villus culture. The chances of finding a chromosomally abnormal fetus (mosaic trisomy 16, triploidy) after diagnosis of trisomy 16 in chorionic villi are low but warrant further investigations.     

Postnatal placental confirmation of trisomy 2 and trisomy 16 detected at chorionic villus sampling: A possible association with intrauterine growth retardation and elevated maternal serum alpha-fetoprotein

Detection of trisomy 2 and trisomy 16 mosaicism through chorionic villus sampling (CVS) is not an infrequent finding. We describe here two cases, one of non-mosaic trisomy 2 and the other of high level mosaicism for trisorny 16. Amniocentesis in both cases demonstrated non-mosaic 46,XY karyotypes. Each pregnancy continued to delivery of liveborn, normal-appearing boys; both pregnancies were complicated by severe intrauterine growth retardation (IUGR). Postnatal studies of placental biopsies in both cases confirmed the original CVS findings, whereas cord blood karyotypes were normal in both boys. Both children have demonstrated adequate catch-up growth.     

Maternal uniparental heterodisomy for chromosome 2: detection through ‘atypical’ maternal AFP/hCG levels,with an update on a previous case

We report a case of maternal uniparental disomy 2, detected through routine screening of placental karyotypes following the finding of ‘atypical’ AFP/hCG levels in the second trimester, with intrauterine growth retardation (IUGR) but otherwise normal outcome at term. Although the child remained small, subsequent early physical and mental development has also been normal. Additionally, we report long-term follow-up of an earlier case, again with relatively normal physical and mental development. The significance of atypical AFP/hCG results and the predictive value of prenatal testing for UPD2 in trisomy 2 confined placental mosaicism (CPM) cases are discussed. Copyright © 2001 John Wiley & Sons, Ltd.     

Managing twins discordant for fetal anomaly

An excess of structural anomalies is observed in twins compared to singletons. Approximately 1–2% of twin pregnancies may face the dilemma of expectant management versus selective termination following diagnosis of an anomaly affecting only one fetus. If the option of selective fetocide is considered, the main variable determining the technique to achieve this aim is chorionicity. In a dichorionic pregnancy, passage of substances from one twin into the circulation of the co-twin is unlikely due to the lack of placental anastomoses, hence KCl can be injected safely into the circulation of the affected twin to produce fetal asystole. In monochorionic twin pregnancies, selective termination needs to be performed by ensuring complete and permanent occlusion of both the arterial and venous flows in the umbilical cord of the affected twin, in order to avoid acute haemorrhage from the co-twin into the dying fetus, which may lead to death or organ damage. Bipolar cord coagulation under ultrasound guidance is associated with approximately 70–80% survival rates. Copyright © 2005 John Wiley & Sons, Ltd.     

Trisomy 16 detected at chorion villus sampling

Trisomy 16 detected at chorion villus sampling (CVS) may reflect the placental but not the fetal karyotype. We describe a case in which the pregnancy continued until intrauterine death at 37 weeks. Cytogenetic study of two placental samples showed 47, +16 and 46,XX; the fetus was morphologically grossly normal, but fetal tissue culture was unsuccessful. Conservative management may be appropriate when trisomy 16 is detected at CVS and the pregnancy is normal ultransonographically.     

A second case of intrauterine growth retardation and primary hypospadias associated with a trisomy 22 placenta but with biparental inheritance of chromosome 22 in the fetus

We report a case of severe intrauterine growth retardation (IUGR) and hypospadias in association with trisomy 22 diagnosed following chorionic villus sampling (CVS). Subsequent analysis of amniotic fluid cultures showed a normal male karyotype, 46,XY. As a previous case had been reported with similar abnormalities, in association with maternal uniparental disomy (UPD) 22, molecular studies were also performed. Microsatellite marker studies showed biparental inheritance. Follow-up studies after delivery showed a normal cell line in lymphocytes with the trisomy appearing to be confined to the placenta. The present case concurs with other earlier reports that maternal UPD for chromosome 22 has no impact on the phenotype. The features seen in the fetus are most likely the result of placental dysfunction due to trisomy, tissue-specific mosaicism and/or the effects of local growth restriction. Copyright © 2002 John Wiley & Sons, Ltd.     

Aortic isthmus Doppler velocimetry: role in assessment of preterm fetal growth restriction

Intrauterine fetal growth restriction (IUGR) is an important pregnancy complication associated with significant adverse clinical outcome, stillbirth, perinatal morbidity and cerebral palsy. To date, no uniformly accepted management protocol of Doppler surveillance that reduces mortality and cognitive morbidity has emerged. Aortic isthmus (AoI) evaluation has been proposed as a potential monitoring tool for IUGR fetuses. In this review, the current knowledge of the relationship between AoI Doppler velocimetry and preterm fetal growth restriction is reviewed. Relevant technical aspects and reproducibility data are reviewed as we discuss AoI Doppler and its place within the existing repertoire of Doppler assessments in placental insufficiency. The AoI is a link between the right and left ventricles which perfuse the lower and upper body, respectively. The clinical use of AoI waveforms for monitoring fetal deterioration in IUGR has been limited, but preliminary work suggests that abnormal AoI impedance indices are an intermediate step between placental insufficiency-hypoxemia and cardiac decompensation. Further prospective studies correlating AoI indices with arterial and venous Doppler indices and perinatal outcome are required before encorporating this index into clinical practice. Copyright © 2010 John Wiley & Sons, Ltd.     

Confined placental mosaicism in CVS and pregnancy outcome

The perinatal outcome of 26 patients with confined placental mosaicism (CPM) detected in chorionic villus sampling (CVS) who wished to continue their pregnancies was compared with that of two controls per patient matched for age and parity (n=52). There were no significant differences in birth weight or gestational age at delivery between patients with CPM and controls. There were no cases of intrauterine growth retardation (IUGR) in the CPM patients as compared with two (2/52, 3·8 per cent) in the control group (P>0·05). There was no significant increase in fetal loss between the study group (1/26, 3·6 per cent) and the controls (1/52, 1·9 per cent) (P>0·05).     

The normal fetus of an acardiac twin pregnancy: Perinatal management based on echocardiographic and sonographic evaluation

Experience with three prenatally diagnosed pregnancies complicated by an acardiac twin reveals that ultrasonography and echocardiography are helpful in detecting early signs of in-utero congestive heart failure in the normal twin. The use of Doppler blood flow analysis to determine direction of blood flow, post-mortem placental and fetal angiography, and umbilical cord blood gas determination provided proof that retrograde arterial perfusion occurs in the acardiac fetus. In a fourth pregnancy, an experimental approach to occlude the acardiac twin's umbilical cord was attempted, but was unsuccessful.     

Confirmation of CVS mosaicism in term placentae and high frequency of intrauterine growth retardation association with confined placental mosaicism

About 2 per cent of specimens from chorionic villus sampling (CVS) analysed either on direct preparation of cytotrophoblast cells or afterculture of mesenchymal stroma reveal confined placental mosaicism (CPM), most commonly involving chromosomal trisomy. A significantly higher rate of prenatal loss (22 per cent) as well as the presence of intrauterine growth retardation (IUGR) has been reported among pregnancies with CPM. To evaluate more precisely the effect of these aneuploid cell lines confined to the placenta on intrauterine fetal growth and fetal survival, we have studied 34 term placentae from pregnancies with CPM diagnosed on CVS and confirmed identical mosaicism in 17 of these placentae. There was a direct correlation between a high number of aneuploid cells present at CVS and a high likelihood of their detection in term placenta. Also, the proportion of aneuploid cells in the mosaic term placentae correlated with that observed in CVS specimens. Among 17 gestations with confirmed CPM at delivery, there were six cases of IUGR identified, five in liveborns and one associated with intrauterine death.     

Elevated alpha-fetoprotein and human chorionic gonadotropin as a marker for placental trisomy 16 in the second trimester?

In a series of 2961 consecutive cases with second-trimester biochemical triple screening for Down's syndrome and neural tube defect (NTD), ten (0.3 per cent) showed an apparent increased risk for both conditions. Three cases had chromosomal abnormalities, namely trisomy 16 confined to the placenta. Since placental trisomy 16 as well as cases with increased alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) are associated with (intrauterine growth retardation (IUGR), oligohydramnios, and fetal demise, at least some cases with this atypical biochemical profile could be explained by this chromosomal abnormality. From our results we recommend that in cases with increased risk for both Down's syndrome and NTD, fetal karyotyping should preferably be done on a placental biopsy, especially when ultrasound in the absence of anomalies demonstrates early IUGR.     

Female pseudohermaphroditism in a fetus with a deletion 9(q22.2q31.1)

Interstitial deletions of chromosomal region 9q are rarely seen. We report the first prenatal diagnosis of a de novo interstitial deletion 9q. The fetus was karyotyped for intrauterine growth retardation (IUGR). Conventional and molecular cytogenetics showed female karyotype with a de novo deletion of the chromosomal region 9(q22.2q31.1) leading to a partial monosomy 9q. At autopsy, the fetus showed growth retardation, dysmorphy, and a female pseudohermaphroditism. These results suggest that a gene(s) for genital development reside in chromosomal region 9q22.2q31.1. Copyright © 2002 John Wiley & Sons, Ltd.     

Intrauterine growth restriction (IUGR): biometric and Doppler assessment

Intrauterine growth restriction (IUGR) is a common complication in pregnancy and influences morbidity and mortality at all stages of life. Historically, the management of IUGR has been dependent on antenatal biophysical testing and umbilical artery Doppler studies. With recent Doppler studies of the fetal central circulation, including intracardiac flows and the ductus venosus, better timing of delivery to minimize morbidity may be possible. This review will provide the reader with tools to diagnose IUGR, more accurately date the IUGR pregnancy with poor dating criteria, and better assess the condition of the IUGR fetus. A brief review of animal models of IUGR is presented to demonstrate research directions for answering human clinical questions and potentially carrying therapeutic intervention from the bench to the bedside. Copyright © 2002 John Wiley & Sons, Ltd.     

Confined placental mosaicism for trisomy 14 and maternal uniparental disomy in association with elevated second trimester maternal serum human chorionic gonadotrophin and third trimester fetal growth restriction

A case of confined placental mosaicism (CPM) and maternal uniparental isodisomy 14 identified after placental karyotype revealed trisomy 14 in a newborn with intrauterine growth restriction (IUGR) and minor dysmorphic features is reported. During the second trimester of the pregnancy, multiple marker screening revealed an increased risk for Down syndrome of >1 in 10. The maternal serum human chorionic gonadotrophin (MShCG) was markedly elevated at 4.19 MoM. Amniocentesis revealed a normal 46,XX karyotype. Fetal growth restriction has been associated with elevated MShCG and placental aneuploidy with CPM for chromosomes 2, 7, 9 and 16. The present case of CPM for chromosome 14 was also associated with fetal growth restriction and elevated second trimester MShCG, suggesting a common link. Further studies need to be done to determine if indeed elevation of second trimester MShCG is associated with increased risk of CPM. The present case again demonstrates the need to perform placental karyotype in unexplained fetal growth restriction. Copyright © 2001 John Wiley & Sons, Ltd.     

Human maternal uniparental disomy for chromosome 16 and fetal development

Two severely growth-retarded fetuses found to have maternal uniparental disomy (UPD) for chromosome 16 and trisomy 16 placental mosaicism both had an unfavourable outcome. Antenatally, the first case was complicated by an unexplained raised maternal serum alpha-fetoprotein concentration, preterm premature rupture of the membranes, and growth retardation detectable at 21 weeks' gestation, whilst the other had an unexplained raised maternal serum human chorionic gonadotrophin level, a two-vessel cord on ultrasound, and cessation of growth at 25 weeks. At post-mortem, both babies had an imperforate anus. Fetal maternal UPD may explain the poor outcome that occurs in some cases of confined placental mosaicism for chromosome 16 and is also associated with specific fetal abnormalities.     

Prenatal ultrasound diagnosis of congenital heart disease associated with intrauterine growth retardation. A report of 2 cases

Two fetuses with extreme growth retardation (IUGR) of 31 and 34 weeks gestation were studied using a combination of two dimensional echocardiography (2DE), pulse wave Doppler (PWD) and differential measurement of the instantaneous vessel diameter techniques. The first fetus was diagnosed as having univentricular heart or possible double outlet right ventricle (DORV). Descending aorta blood flow was reduced as was indexing for weight. The second fetus was diagnosed as having univentricular heart with periodic bigeminal and trigeminal rhythm. Descending aorta blood flow was measured on two occasions and was reduced both times. Indexing for weight was within normal limits the first time and showed gross reduction on the second occasion prior to fetal demise. Fetal death occurred in both cases at 34 weeks gestation. Cardiovascular evaluation in fetuses with IUGR is useful as the detection of severe congenital cardiac abnormalities may substantially alter the management of these pregnancies, in particular caesarean section may be avoided when the prognosis for the fetus is considered hopeless.     

Intermittent absent and reversed umbilical artery flows in appropriately grown monochorionic diamniotic twins in relation to proximate cord insertion: A harmful combination?

Objective

To compare the prevalence of intermittent absent or reversed end-diastolic flow (iAREDF) in the umbilical artery in appropriately grown monochorionic diamniotic (MCDA) pregnancies with and without proximate cord insertion (PCI), and to evaluate pregnancy outcome.

Methods

The prevalence of iAREDF in MCDA pregnancies with PCI (n = 11) was compared with a control group without PCI (n = 33). PCI was defined as a distance between the cord insertions below the fifth percentile. Placental sharing, number, and diameter of anastomoses were assessed by placental examination. Pregnancy outcome was evaluated.

Results

iAREDF was present in 7/11 PCI pregnancies, compared with 0/33 in the control group (P ≤ .01). All PCI pregnancies and 94% of controls had arterioarterial (AA)-anastomoses (P = .56), the diameter was larger in the PCI group, respectively 3.3 vs 2.1 mm (P = .03). Three cases with iAREDF had adverse outcome, two resulted in fetal death of which one with brain damage in the co-twin, another underwent early premature emergency section for fetal distress.

Conclusion

iAREDF occurs in a large proportion of MCDA pregnancies with PCI and is related to the diameter of the AA anastomosis. We hypothesize that iAREDF in appropriately grown MCDA twin pregnancies reflects an unstable hemodynamic balance with an increased risk for fetal deterioration. Whether outcome in these pregnancies can be improved by altered management requires further investigation.

     

Heterogeneity in fetal akinesia deformation sequence (FADS): autopsy confirmation in three 20–21-week fetuses

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified. Copyright © 2002 John Wiley & Sons, Ltd.