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. Received December 1, 1999; accepted February 15, 2000.     

The Roach muscle bundle and umbilical cord coiling

OBJECTIVE: To determine if presence of the Roach muscle, a small muscle bundle lying just beside the umbilical artery, contributes to umbilical cord coiling. METHODS: 251 umbilical cords were examined. The umbilical coiling index (UCI) was calculated as the number of coils divided by the cord length in cm. Cords were classified as hypocoiled (UCIp90). On microscopic examination of a cross section of the cord, absence or presence of a Roach muscle was determined. The t-test for independent samples and logistic regression were used for statistical analysis. RESULTS: A Roach muscle was observed in 101 cords. The mean UCI was higher in cords with the muscle bundle (0.23 coils/cm) than in cords without a muscle (0.18 coils/cm). Difference in mean: 0.05 coils/cm (95% C.I. 0.01-0.09). OR for hypercoiling in presence of the muscle was 2.98 (95% C.I. 1.57-5.64). OR for hypocoiling in the presence of the muscle was 1.49 (95% C.I. 0.79-2.81). CONCLUSIONS: Our results suggest that presence of a Roach muscle bundle contributes to umbilical cord coiling. Given the divergence in umbilical cord coiling within subgroups with or without this muscle, other factors must play a more dominant role.     

The relation between umbilical cord characteristics and the outcome of external cephalic version

Background

Umbilical cords of fetuses in breech presentation differ in length and coiling from their cephalic counterparts and it might be hypothesised that these cord characteristics may in turn affect ECV outcome.

Aim

To investigate the relation between umbilical cord characteristics and the outcome of external cephalic version (ECV).

Study design

Prospective cohort study.

Subjects

Women (> 35 weeks gestation) with a singleton fetus in breech presentation, suitable for external cephalic version. Demographic, lifestyle and obstetrical parameters were assessed at intake. ECV success was based on cephalic presentation on ultrasound post-ECV. Umbilical cord length (UCL) and umbilical coiling index (UCI) were measured after birth.

Outcome measure

The relation between umbilical cord characteristics (cord length and coiling) and the success of external cephalic version.

Results

ECV success rate was overall 79/146 (54%), for multiparas 37/46(80%) and for nulliparas 42/100 (42%). Multiple logistic regression showed that UCL (OR: 1.04, CI: 1.01-1.07), nulliparity (OR: 0.20, CI: 0.08-0.51), frank breech (OR: 0.37, 95% CI: 0.15-0.90), body mass index (OR: 0.85, CI: 0.76-0.95), placenta anterior (OR: 0.27, CI: 0.12-0.63) and birth weight (OR: 1.002, CI: 1.001-1.003) were all independently related to ECV success.

Conclusions

Umbilical cord length is independently related to the outcome of ECV, whereas umbilical coiling index is not.     

Vascular endothelial growth factor and angiogenin levels during fetal development and in maternal diabetes

We evaluated the concentrations of vascular endothelial growth factor (VEGF) and angiogenin in the umbilical cord blood from 14 fetuses with erythroblastosis or alloimmune thrombocytopenia and at birth from 28 preterm fetuses, from 42 healthy term fetuses, and from 24 term fetuses born to mothers with insulin-treated diabetes. A correlation appeared between VEGF and angiogenin levels (r = 0.44, p = 0.038). The gestational age correlated with both VEGF (r = 0.38, p = 0.0008) and angiogenin levels (r = 0.80, p = 0.0001). The concentration of VEGF was lower in fetuses born to mothers with insulin-treated diabetes than in the healthy term fetuses (p = 0.0028), but this difference was absent for angiogenin (p > 0.05). In conclusion, in umbilical cord plasma, a developmental increase was evident in concentrations of VEGF and angiogenin during the last trimester of gestation. That the umbilical cord VEGF level was lower in term fetuses born to mothers with diabetes than in term fetuses of healthy mothers may be associated with an aberrant fetal vascular development in diabetic pregnancies.     

Strangulation of the Umbilical Cord by Amniotic Bands: Report of 6 Cases and Literature Review

The amniotic band syndrome is the triad of amnion-denuded placenta; fetal attachment to or entanglement by amniotic remnants; and fetal deformation, malformation, or disruption. Theories of pathogenesis and etiology of the syndrome are discussed.

Amniotic bands occur in 1 of every 5000-15,000 births and are demonstrable in 1-2% of malformed infants. Nearly 10% of cases include umbilical cord strangulation. Six cases of umbilical cord strangulation by amniotic bands are presented, and 57 previously reported cases are reviewed. Two of the 63 were liveborn and 61 were stillborn, 3 of whom died intrapartum. Thirty had associated fetal abnormalities. Five were from multiple gestations. Outcome of the co-twin was determined by its presence within the same amniotic sac. Four fetuses beyond 28 weeks had short cords and were the only malformed fetuses in this age group. The earlier in gestation that amniotic bands form, the greater the likelihood of associated fetal abnormalities. All but 2 of 28 less than 32 weeks and only 4 of 35 greater than 32 weeks were malformed. A marked male predominance was noted in the former group, perhaps because the larger size and/or more vigorous movements of male fetuses promote early amnion rupture.     

Strangulation of the umbilical cord by amniotic bands: report of 6 cases and literature review

The amniotic band syndrome is the triad of amnion-denuded placenta; fetal attachment to or entanglement by amniotic remnants; and fetal deformation, malformation, or disruption. Theories of pathogenesis and etiology of the syndrome are discussed. Amniotic bands occur in 1 of every 5000-15,000 births and are demonstrable in 1-2% of malformed infants. Nearly 10% of cases include umbilical cord strangulation. Six cases of umbilical cord strangulation by amniotic bands are presented, and 57 previously reported cases are reviewed. Two of the 63 were liveborn and 61 were stillborn, 3 of whom died intrapartum. Thirty had associated fetal abnormalities. Five were from multiple gestations. Outcome of the co-twin was determined by its presence within the same amniotic sac. Four fetuses beyond 28 weeks had short cords and were the only malformed fetuses in this age group. The earlier in gestation that amniotic bands form, the greater the likelihood of associated fetal abnormalities. All but 2 of 28 less than 32 weeks and only 4 of 35 greater than 32 weeks were malformed. A marked male predominance was noted in the former group, perhaps because the larger size and/or more vigorous movements of male fetuses promote early amnion rupture.     

Induction of necrotizing funisitis by fetal administration of intravenous granulocyte-colony stimulating factor and intra-amniotic endotoxin in premature fetal sheep

The purpose of the present study was to determine whether experimental intrauterine inflammation could induce necrotizing funisitis, a severe, chronic inflammation of the umbilical cord. Fetuses, randomly divided into four groups (n = 4 each), were infused with 50 mug/d of granulocyte-colony stimulating factor (G-CSF) intravenously on d 125-129 of gestation (G-CSF group), 20 mg of endotoxin into the amniotic cavity on d 127 gestation (endotoxin group), both G-CSF and endotoxin (G-CSF + endotoxin group), or only saline (control group). On d 130 of gestation, the umbilical cords were processed for histologic analysis, scored for degree of inflammation, and compared statistically. At birth, the blood polymorphonuclear leukocyte counts in G-CSF and G-CSF + endotoxin groups were significantly higher than those in endotoxin and control groups (p < 0.05). The inflammatory score of the umbilical cord in G-CSF + endotoxin group was significantly higher than those in the other three groups (p < 0.05). All the fetuses in G-CSF + endotoxin group had necrotizing funisitis, but none of the fetuses in the other three groups developed this condition. An increase in blood polymorphonuclear leukocytes before their activation in the umbilical cord is probably essential for experimentally inducing necrotizing funisitis.     

Incidence and types of congenital cardiovascular malformations in Japanese trisomy 21 fetuses around 20 weeks

ABSTRACT In order to clarify the incidence and types of cardiovascular malformations in Japanese trisomy 21 fetuses, seventeen cases were investigated at around 20 weeks of pregnancy. Cardiovascular malformations were observed in 8 of 17 cases (47.1%). The incidence of cardiovascular malformations was not greatly different from the estimated incidence (50%) in Japanese children with Down syndrome. The preferential elimination would not exist in trisomy 21 fetuses around 20 weeks relevance to cardiovascular malformations. Atrioventricular (AV) septal defect, tetralogy of Fallot and Ebstein's anomaly were observed in one case each. Bicuspid aortic valve and abnormal branching of the aortic arch were present in three and two cases, respectively. AV septal defect, which is perceived as a specific malformation of trisomy 21, was not recognized in high frequency in the present fetal study. A 13-week-old fetus showed multiple malformations; AV septal defect, tetralogy of Fallot and dysplastic bicuspid aortic valve. This case displayed an early morphology of AV septal defect which has rarely been reported in trisomy 21 fetuses. Possible pathogenesis of AV septal defect was discussed in relation to animal models of human trisomy 21. The present study indicated     

Alteration of arterial gas composition by positive pressure ventilation in the unanesthetized fetal lamb in utero

To study the effectiveness of in utero ventilation in altering fetal arterial gas composition, we ventilated 15 near-term fetal lambs with a range of inspired gas mixtures. To accomplish this, double lumen nasogastric tubes were surgically placed in the tracheas of 15 near-term (135 days' gestation) fetal lambs. After 4 +/- 1 SD postoperative days, the fetuses were respired by positive pressure ventilation. 13 of these fetuses were also ventilated with their umbilical cords completely occluded. Ventilation was maintained for an average of 4.5 h (range 2.5-7.5 h). All 15 fetuses were effectively oxygenated on room air when exposed to a small net positive end expiratory pressure. In fetuses with intact umbilical cords, PaO2 could be maintained at levels between 11 and 280 mm Hg and PaCO2 from 36 to 139 mm Hg by altering the inspired O2 and CO2 with a gas mixing device. During umbilical cord occlusion, PaO2 was regulated from 2.2 to 103 mm Hg and PaCO2 from 37 to 187 mm Hg.     

A FETUS WITH DOWN SYNDROME AND INTRATUBULAR GERM CELL NEOPLASIA

A 22-week-old fetus with trisomy 21 demonstrated intratubular germ cell neoplasia. This is the second report of in situ testicular neoplasia in a fetus with trisomy 21, suggesting that the mechanism responsible for the possible excess of testicular germ cell tumors that occur in Down syndrome is operative in early fetal life. Because no examples of neonatal testicular germ cell tumor in trisomy 21 have been reported, we suggest that this in situ neoplasm may disappear during gestation, such as the trisomy 21-associated transient myeloproliferative syndrome does shortly after birth. This disappearance may be due to a controlled regression phenomenon.     

Umbilical cord length in Down's syndrome

Fetal motor activity is believed to influence umbilical cord growth. As Down's syndrome is associated with hypotonicity and reduced fetal activity, we hypothesized that newborn infants with this syndrome have short umbilical cords. We identified 21 infants with Down's syndrome and compared each individual cord length to mean standard values derived from the same population and matched for sex, race, and gestational age. Infants with Down's syndrome were found to have significantly shorter umbilical cords (mean of 45.1 cm compared with 57.3 cm for matched standards). It is not clear whether their cords are shorter on the basis of decreased fetal activity, genetics, or both. If it is on the basis of decreased fetal activity, it would be interesting to see if those with the shortest cords (presumed to have been the most hypoactive in utero) could be predicted to have worse neurodevelopmental outcomes.     

Biometry of face and brain in fetuses with trisomy 21

The aim of this study was to specify the early setting of the particular craniofacial morphology in Down syndrome during the fetal period from data based on postmortem examinations. The study included 1277 fetuses at 15-38 gestational weeks (GW): 922 control fetuses and 355 fetuses with trisomy 21, selected from fetopathology units in Paris. Body weight (BW) and nine dimensions of the face, skull, and brain were recorded: the outer and inner canthal distances (OCD, ICD), biparietal diameter (BPD), head circumference (HC), brain weight (BrW), occipitofrontal diameters of left and right hemispheres (lOFD, rOFD), weight of the infratentorial part of the brain (IBW), and maximal transversal diameter of the cerebellum (CTD). Four ratios were computed: BPD/HC, OCD/BPD, BrW/BW, IBW/BrW. Differences between trisomic fetuses and control fetuses were tested by age interval. Results showed that BW, rOFD, and lOFD were lower in trisomic fetuses as early as 15 GW. Cerebellar hypoplasia included lower IBW and CTD in trisomic fetuses. The IBW/BrW ratio was higher in trisomic fetuses, showing that growth restriction affected the infratentorial part of the brain less than the supratentorial part. Early brachycephaly was found in trisomic fetuses, with higher values of BPD and BPD/HC from 15 GW. ICD and OCD were not significantly different in the two groups, but OCD/DBP ratio was lower in trisomic fetuses. These results confirm the early phenotypical expression of trisomy 21 on craniofacial morphology, associated with a marked restriction of brain growth, especially in the supratentorial part.     

Effect of amnionitis on the complement system of preterm infants

The development of the complement system was studied by quantitation of total hemolytic complement activity (CH50), C1q, C3, C4, and C3 split product (C3d) in cord plasma of nine human fetuses (17-22 weeks of gestation), 110 preterm (24-36 weeks of gestation) and 30 term neonates. The complement levels were analyzed in relation to various illnesses of preterm infants. Histological examination of the placenta revealed a higher incidence of amnionitis in the placenta of less than 34 gestational weeks. In cases without amnionitis, there were significant correlations between complement levels and gestational age. In cases with amnionitis, the complement system was activated even in infants of less than 28 weeks gestation. The complement levels correlated with the extent of the inflammation in the placentas and umbilical cords except for C1q. In infants with Wilson-Mikity syndrome, complement levels other than C1q were significantly elevated in comparison with those of infants with respiratory distress syndrome. In the group of preterm infants without amnionitis, no differences were found between infants with intrauterine growth retardation and those with growth appropriate for gestational age.     

The water content of the human umbilical cord

105 umbilical cords from 53 term and 52 preterm newborn infants were freeze-dried after removal of the blood vessels, to determine the water content. The mean umbilical cord water content (i.e. mean of water content of fetal and placental ends of the cord), was 88.9% (SD 2.73) for term cords and 91.9% (SD 1.99) for preterm cords. The mean water content fell with increasing gestation. The fetal end of the cord had a significantly higher water content than the placental end. Similarly, the volume of a 4-cm length segment of cord was significantly greater at the fetal than placental end. There was no correlation between cord water content or volume and several other variables including birthweight, size for gestational age and placental weight. These observations suggest a metabolically active role for the umbilical cord.     

Plasma amyloid beta protein 1-42 levels in fetuses with Down syndrome

BACKGROUND: The presence of amyloid plaques in the brains of people with Down syndrome is correlated with the severity and the progression of the disease. The core of the plaques is an amyloid beta (A beta) protein. If a relationship between fetal levels and the presence and severity of the disease could be determined, consideration of an early intervention to reduce brain damage can be proposed. AIM: To study plasma amyloid beta 1-42 levels in fetuses with Down syndrome. STUDY DESIGN: Fetal plasma amyloid beta 1-42 levels were measured using a commercially available immunoassay. The sample size was previously calculated to show a difference with an alpha level of 0.05 and a power (1-beta) of 90%. SUBJECTS: Thirteen fetuses with Down syndrome and 17 controls (22.3+/-2.0 and 21.6+/-1.2 weeks of gestation, respectively). OUTCOME MEASURES: Fetal plasma amyloid beta 1-42 levels. RESULTS: There was no significant difference in plasma amyloid beta 1-42 levels between fetuses with Down syndrome and those with a normal karyotype (193.1+/-48.0 vs. 194.6+/-15.6 pg/mL, respectively). CONCLUSIONS: This result does not support the hypothesis that A beta 1-42 may be related to the severity of brain damage in newborns with Down syndrome. The high levels of this peptide in fetuses without Down syndrome favour a physiological role of these peptides during brain development.     

Serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in healthy newborn infants and healthy young through elderly adults

AIM: To determine the levels of serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in different age groups. METHODS: Serum samples from 70 healthy newborn infants, 80 blood donors and 81 healthy elderly individuals were analysed using a nephelometric method. The 231 samples were grouped as follows: 35 umbilical cords, 35 newborns, 48 young adults, 28 middle-aged adults, and 85 elderly adults. RESULTS: Serum levels of both SAA and hsCRP were lower in umbilical cords than in the newborns and young, middle-aged and elderly adults (p<0.0001). The SAA and hsCRP levels were comparable in newborns, and young and middle-age adults, but higher in elderly adults (p<0.0001-0.03). SAA (r2=0.159, p<0.0001) and hsCRP (r2=0.059, p<0.0001) were positively correlated with age and to each other (r2=0.385, p<0.0001). CONCLUSION: Serum levels of SAA and hsCRP in umbilical cord blood are close to the detection limit and lower than in the other age groups investigated. The elderly have generally higher levels than the younger age groups, which require higher decision levels in inflammatory diseases, including infections. In newborns and young and middle-aged adults, the lower decision levels of 10 mg/l for SAA and 5 mg/l for CRP are suggested.     

Fetal and neonatal thrombopoietin levels in alloimmune thrombocytopenia

Thrombopoietin (Tpo) is the main hematopoietic growth factor for platelet production. Plasma Tpo levels in autoimmune thrombocytopenic patients are normal or slightly elevated. Although thrombocytopenia exists, Tpo levels are not increased because the produced megakaryocytes and platelets can bind circulating Tpo, thereby normalizing Tpo levels. In this study, plasma samples from fetuses and neonates with neonatal alloimmune thrombocytopenia (NAIT), a different form of immune thrombocytopenia, were measured. Umbilical cord samples from 50 fetuses before treatment because of severe thrombocytopenia and 51 fetuses after treatment, and peripheral blood samples of 21 untreated newborns with NAIT were analyzed. As controls, plasma Tpo levels were determined in 21 umbilical cord samples of 14 nonthrombocytopenic fetuses with hemolytic disease resulting from red blood cell alloimmunization and in umbilical cord samples of 51 healthy newborns. The values were also compared with the plasma Tpo levels in 193 healthy adults. Mean Tpo levels from the groups of fetuses and neonates, including both NAIT and control plasma, were slightly but significantly elevated compared with levels in healthy adults. Tpo levels in NAIT samples were not significantly different from the levels in hemolytic disease samples or in samples from healthy newborns. Thus, as in autoimmune thrombocytopenic patients, normal Tpo levels are present in NAIT patients.     

Association of trisomy 21 and gonosomal trisomy. Apropos of 2 cases

The existence of double autosomal trisomy is exceptional in a newborn child: --Down syndrome and trisomy 18. --Down syndrome and trisomy 13. On the other hand, the association of an autosomal trisomy, generally Down syndrome with gonosomal trisomy, is less rare with an extra X (triplo X, Klinefelter) or an extra Y. The association of Down syndrome with Turner XO syndrome (autosomal gonosomal association) doesn't insert in the subject, and has been described only once in the literature.     

Umbilical cord stricture and overcoiling are common causes of fetal demise.

Although umbilical cord stricture and umbilical cord overcoiling have been established as causes of intrauterine fetal demise, relatively few studies addressed this issue, most of them being case reports. We reviewed a total of 268 fetal autopsies during a 3-year period from 1998 to 2001. One hundred thirty nine cases of fetal demise including spontaneous abortion were identified. Nineteen percent (26 of 139) were associated with umbilical cord stricture, overcoiling, or a combination of both. Stricture of the umbilical cord was defined as a decrease in diameter in relation of the remaining umbilical cord; overcoiling as 0.3 coil/cm or greater. Fetal demise most commonly occurred in the second trimester, with a mean gestation age of 21 weeks. The average maternal age was 33 years; 15% had a prior fetal demise. We found that 77% (20 of 26) of these cases had umbilical cord stricture only or with overcoiling, 23% (6 of 26) had umbilical cord overcoiling alone. Localized deficiency of Wharton's jelly and increased collagen were found in all cases with umbilical cord stricture with or without overcoiling. In patients with umbilical cord overcoiling alone, 25% had Wharton's jelly deficiency; half of them had increased collagen deposition in the umbilical cords. The placenta was reviewed for secondary thrombosis of the vessels of the chorionic plate. Thrombosis of the vessels of the chorionic plate was noted in 54% of the patients. Our study suggests that umbilical cord stricture and cord overcoiling may represent two distinct pathological entities commonly causing fetal demise. This observation reinforces the importance of a fetal autopsy with careful examination of the placenta and umbilical cord with documentation of the cord coil index.