Geoffrey A. Machin

Abnormal Umbilical Cord Coiling Is Associated with Adverse Perinatal Outcomes

The normal umbilical cord coil index is one coil/5 cm, i.e., 0.2 ± 0.1 coils completed per cm. We report the frequency and clinical correlations of abnormally coiled cords among 1329 cases referred to our placental pathology services. Twenty-one percent of cords were overcoiled and 13% were undercoiled. Abnormal cord coiling was seen at all gestational ages. Principal clinical correlations found in overcoiled cords were fetal demise (37%), fetal intolerance to labor (14%), intrauterine growth retardation (10%), and chorioamnionitis (10%). For undercoiled cords, the frequencies of these adverse outcomes were 29%, 21%, 15%, and 29%, respectively. Abnormal cord coiling was associated with thrombosis of chorionic plate vessels, umbilical venous thrombosis, and cord stenosis. Thus, abnormal cord coiling is a chronic state, established in early gestation, that may have chronic (growth retardation) and acute (fetal intolerance to labor and fetal demise) effects on fetal well-being. The cause of abnormal cord coiling is not known. Its effects on neurological status of survivors are also unknown. Antenatal detection of abnormal cord coil index by ultrasound could lead to elective delivery of fetuses at risk, thereby reducing the fetal death rate by about one-half. We recommend that the cord coil index become part of the routine placental pathology examination.

Twin-twin transfusion syndrome: The 'select' procedure

Objectives: Twin-twin transfusion syndrome (TTTS) is associated with a high risk of perinatal morbidity and mortality. The condition results from intertwin vascular connections in the shared placenta. We report here a case of early, severe TTTS that failed to respond to serial amniocenteses and that was successfully treated by means of superselective laser coagulation. Methods: A causative arteriovenous anastomosis was identified by means of prenatal obstetrical sonography, using color and spectral Doppler techniques. At fetoscopy, performed at 23 weeks’ gestation, laser occlusion of only this connection was achieved. Results: This therapeutic intervention resulted in rapid resolution of all evidence of TTTS and a successful pregnancy outcome, with subsequent delivery of 2 healthy infants at 33 weeks’ gestation. Conclusions: The potentially fatal pathophysiology of TTTS was reversed by interruption of a single arteriovenous connection. We have termed this the sonographically evaluated, laser-endoscopic coagulation for twins (‘Select’) procedure.

The Prevalence of Chronic Deciduitis in Cases of Preterm Labor without Clinical Chorioamnionitis

Preterm labor is a major cause of perinatal mortality and morbidity, and in approximately 30% of cases a clinical cause is not identified. Acute chorioamnionitis is found histologically in a significant percentage of placentas from preterm deliveries, and the mother is often asymptomatic. Although such subclinical acute chorioamnionitis is known to play a role in preterm labor, this study explores the hypothesis that chronic deciduitis with plasma cells is seen more frequently in cases of preterm labor than in control placentas. Thirty-nine singleton placentas from patients with idiopathic preterm labor were examined microscopically and compared in a blinded fashion with 39 gestational age-matched control placentas. Cases of clinical acute chorioamnionitis and known chronic maternal diseases were excluded. Thirty-nine control singleton placentas were obtained from patients undergoing induction of labor for fetal structural abnormalities, excluding aneuploidy. The presence or absence of acute chorioamnionitis, acute fetal inflammatory response, chronic deciduitis, chronic villitis, infarction, and decidual vasculopathy was noted. Immunohistochemical staining was undertaken to further define leukocyte subtypes. Forty-one percent of cases and 15% of controls showed chronic deciduitis (P = 0.022). Forty-six percent of cases and 18% of controls showed histologic acute chorioamnionitis (P = 0.015). There were 8 cases demonstrating acute fetal inflammatory response but only 1 control (P = 0.029). Little difference was seen in the distribution of lymphocyte subsets between cases and control placentas. Our findings suggest that chronic deciduitis plays a role in the etiology of some cases of preterm labor.

Maternal Thrombophilias Are Associated with Specific Placental Lesions

Maternal floor infarction (MFI), massive perivillous fibrin deposition (MPVFD), and fetal thrombotic vasculopathy (FTV) are specific placental lesions with associations to recurrent adverse fetal outcomes and with maternal thrombophilia. We studied the frequency of a range of acquired and genetic maternal thrombophilias in MFI (40 cases), MPVFD (87 cases), FTV (7 cases), and FTV+MPVFD (4 cases). Thrombophilias were identified in 16 (40%), 20 (23%), 5 (71%), and 2 (50%) of these lesions, respectively. Seventy-seven percent of the identified thrombophilias were genetic, and 23% were acquired. The most common genetic thrombophilia was protein S deficiency, which constituted 14 of the 36 genetic thrombophilias (39%). We advocate full maternal thrombophilia testing when the diagnosis of MFI, MPVFD, and FTV is made by placental pathology examination. Because of the possible contribution of paternal thrombophilic mutations to the fetal genotype, it would be desirable to test the whole family as well.

Two pairs of male monozygotic twins discordant for Wiedemann-Beckwith syndrome

Wiedemann-Beckwith syndrome (WBS) is a congenital anomaly syndrome which classically consists of exomphalos, macroglossia, and gigantism. The syndrome is also associated with a variety of minor anomalies and affected individuals have an increased risk of developing rare embryonal cell tumors. To date, 15 monozygotic (MZ) twin pairs have been reported of which 13 are discordant for WBS. All except one pair of the discordant WBS twin pairs have been female. We report two pairs of male MZ twins, each discordant for WBS.

Zygosity and placental anatomy in 15 consecutive sets of spontaneously conceived triplets

Most triplets are trizygotic because they result from assisted reproduction. Prognosis is generally good. We analyzed 15 sets of triplets who were conceived spontaneously. Six sets were monozygotic, 7 were dizygotic, and only 2 sets were trizygotic. Considered as 45 twin pairs, 25 pairs (56%) were monozygotic. Twenty percent of these twins died as a result of twin-twin transfusion. Spontaneously conceived triplets have high risks compared with those resulting from assisted reproduction. These risks result from a high proportion of monozygotic embryos, many of whom have monochorionic placentas with vascular anastomoses, causing twin-to-twin transfusion.

Third-Trimester Stillbirths: Correlative Neuropathology and Placental Pathology

Although in recent years placental pathology has been the subject of a wealth of detailed descriptions and diagnostic categorization, systematic correlation of these conditions with the pathology of stillbirth has not been attempted. We examine the relationship between specific inflammatory, maternal, and fetal vascular pathologies and the central nervous system pathology and histological indicators of fetal compromise. Our design was a retrospective case series of 37 3rd-trimester intrauterine fetal deaths. In general, mixed placental pathologies were the rule, with three quarters of the placentas demonstrating combinations of maternal vascular pathology, fetal vascular pathologies, umbilical cord abnormalities, or inflammatory lesions. The range of brain pathology was limited to acute, severe congestion, white matter edema, and neuronal karyorrhexis (pontosubicular necrosis with or without neuronal karyorrhexis at other sites). Established periventricular leukomalacia was present in only 2 cases. The presence of neuronal karyorrhexis or white matter gliosis was correlated with the presence of a high-grade inflammatory lesion and with fetal thymic involution. Neuronal karyorrhexis, but not white matter gliosis, correlated as well with histologically established fetal vascular lesions in the placenta, even once the effect of inflammation was accounted for. Gliosis also correlated with inflammation, meconium staining, and thymic involution. Central nervous system injury may be the end result of complex placental pathologies, and neuronal injury may be a consequence of the fetal inflammatory response. The correspondence between the time courses of histological features of chorioamnionitis, neuronal karyorrhexis, and thymic involution points to irreversible central nervous system injury being common 12–48 hours prior to in utero demise.

X-chromosome inactivation is mostly random in placental tissues of female monozygotic twins and triplets

Patterns of X-chromosome inactivation in chorion, amnion, and cord from 79 pairs of twins were examined. Seven sets of triplets were included in the analysis, both as twin pairs and triplets. Twins were stratified as dizygotic (DZ), monozygotic (MZ), monochorionic, and dichorionic and were selected for birth weight discordance, discordance for congenital anomalies, twin-twin transfusion syndrome, and various patterns of vascular anastomosis. X-inactivation was predominantly symmetric. Chorion was the most likely tissue to show asymmetric X-inactivation and was found most frequently in MZ dichorionic twins. There was no correlation of X-inactivation pattern with the selected clinical criteria. This study does not confirm that asymmetric X-inactivation in embryonic tissues is a common phenomenon in female twins, including monozygotic twins.

Perinatally acquired neonatal tuberculosis : report of two cases

Perinatally acquired neonatal tuberculosis occurs rarely, is difficult to diagnose, may be the indicator of untreated tuberculosis in the mother, and could result in nosocomial transmission to neonatal patients, visitors to neonatal intensive care units, and health care workers. The disease may be more common in certain ethnic and social groups. Neonatal mortality approaches 30%. We report two cases with different outcomes. A neonate was treated for clinical miliary tuberculosis and survived; Mycobacterium tuberculosis was cultured from bronchoscopic washings, maternal genital fluids, and tissues. A second infant died at age 46 days, and autopsy disclosed miliary tuberculosis of lungs, mediastinal and mesenteric nodes, liver, spleen, and bone marrow. The lungs were most severely affected, but the placenta and central nervous system were not involved. The histopathology was not granulomatous. After the diagnosis in the infant, the mother was ascertained to have pulmonary and genital tuberculosis. Fetal and neonatal tuberculosis could be acquired transplacentally as prenatal tuberculous chorioamnionitis, perinatally through aspiration and ingestion of infected maternal genital tissues and fluid, or postnatally through droplet spread from cases of active tuberculosis. These two neonates probably acquired the disease perinatally from maternal genital tuberculosis.

Rapid onset of severe twin-twin transfusion syndrome caused by placental venous thrombosis

We report a case of rapid onset of severe twin–twin transfusion syndrome (TTTS) at 25 weeks gestation in a monochorionic twin pregnancy that was uneventful before that time. Thrombosis of a main venous branch draining several arteriovenous (AV) anastomoses to the donor changed the previous hemodynamic balance that existed between multiple bidirectional AV anastomoses. The opposing AVs became hemodynamically uncompensated and, despite amnioreductions, severe TTTS developed. At 27 weeks a cesarean section was performed because of worsening cardiotocography parameters of both fetuses. Birth weights were 750 and 1840 g, and initial hemoglobin concentrations were 9.2 and 13.4 mmol/liter for donor and recipient, respectively. The recipient twin died 5 months later of an ischemic, necrotic, and perforated small intestine due to a thrombosed superior mesenteric artery. The donor is well at 2.5 years. No abnormalities in several factors associated with thrombophilia, including factor V Leiden mutations, were found in the parents.