Umbilical Cord Accidents

Jason H Collins MD
Charles L Collins MD,BSE
Candace C Collins MD

ABSTRACT

Umbilical Cord Accidents (UCA) are a type of sudden antenatal death syndrome (SADS) which needs study. Most UCA stillbirths are genetically normal and autopsy negative. Ultrasound is capable of identifying UCA prenatally. Case reports have described management of UCA prior to labor such as vasa previa and monoamniotic twin entanglement. Is it time to consider UCA as an important risk factor for stillbirth? What evidence exists which supports a systematic review of all pregnancies for UCA? Can current obstetrical practices benefit prenatally diagnosed UCA and manage the risk of SADS?

An Umbilical Cord Accident (UCA) occurs

when umbilical venous or umbilical arterial blood flow is compromised to a degree that it leads to fetal injury or death. The human umbilical cord is vulnerable to a variety of malformations, lesions, mechanical and iatrogenic events throughout pregnancy, labor and delivery. Medical and lay literature on UCA has accumulated since the Collaborative Perinatal Project (CPP). (1),(2),(3).The CPP data is used by the National Institutes of Health to study current obstetrical issues. Two reviews of UCA from the CPP study including; true knot, nuchal coils, and body loops suggests an association with extremes of umbilical cord length as a fetal risk factor for fetal malformation, injury and stillbirth.(4)(5) A review of stillbirths from the CPP suggests that UCA's (such as nuchal cord, true knot, and prolapse) have at least an incidence of 1.5 stillbirths/1000 births.(6) This review article summarizes the published medical literature on UCA since the CPP. The primary reference list in this review will provide the reader with ready access to secondary source publications before 1960. For each UCA issue such as single umbilical artery (SUA) , reviews were referenced where available (there may be >100 articles on SUA). Encountered during this review were innumerable photos, tables, and drawings which contribute to the understanding of UCA and which can be found within the quoted references.

Since 1960 and the CPP development of ultrasonography, fetal monitoring, animal models of umbilical cord compression and numerous case reports have provided a better understanding of how UCA can affect the fetus. An assimilation of UCA studies and stillbirth studies in humans and animals allows an initial insight into how often UCA's are encountered. Pathologic examination of UCA's and interpretation of fetal monitoring methods adds evidence to UCA being a cause of fetal stress, injury and death. Research is needed into the underlying mechanisms of umbilical cord accidents. The human umbilical cord has been studied since recorded history. Although UCA stillbirth is difficult to prove in humans, it is not uncommon in mammals.(7) One of the first published accounts of an UCA in western medical writings was by William Smellie in his Treatise on Midwifery in 1750, London, England: a nuchal cord associated stillbirth.One of the first published drawings of an UCA was by Andrew Bell in the Encyclopedia Britanica 1st edition 1769 Edinburgh, Scotland, depicting a fetal death with a combination of one nuchal cord, a body loop and a true knot. There are over 25 separate types of UCA's which have been well described and catalogued in current pathology texts. (8),(9),(10),(11) Numerous published case reports since the CPP have described observations associated with witnessed UCA stillbirths. What is suggested by these reports is the fetus may not be dying suddenly. The fetus may have changes in blood supply due to cord compression that it adjusts to and compensates for several hours or days until it no longer can. This suggests there may be time to evaluate and deliver the fetus at risk of an UCA associated stillbirth. Most stillbirths occur antepartum (8/1000) or 60% after 34 wks and 25% occur between 36-40 weeks. UCA's stillbirths tend to occur between 36-38wks, as for most stillbirths.(11),(12),(13),(14),(15),(16),(17),(18) It may also be that a common time of fetal death is during maternal sleep. This event could be related to diurnal rhythms influencing maternal blood pressure (causing hypotension), uterine contractures (reducing uterine blood flow>35%) and fetal cortisol reduction, between 2-4 A.M.(19),(20),(21),(22),(23),(24)

What is the occurrence of UCA associated Stillbirth.
Umbilical cord accidents may occur in 15% or more of all sudden antenatal death syndrome (SADS) cases.(25) From conception to post dates pregnancies the incidence of UCA may be > 35%. Stillbirth studies with pathologic review have suggested that UCA causes fetal death which is in agreement with the CPP's report on UCA's. One case controlled study of unexplained stillbirth determined for UCA the following significant confidence interval , ( OR 6.57 95% CI 1.36 to 31.75). Another large retrospective study of SADS determined with multiple logistic regression that umbilical cord complications were a significant cause of stillbirth (reviewing 68,870 singleton birth files with 3.6 deaths/1000 births excluding congenital malformations).(26),(27) In some studies, UCA was not accepted as a primary cause of stillbirth or unexplained death but were analyzed as potential determinants in the study. In reviews of non US national stillbirth statistics UCA is not clearly delineated as a cause of death and do not always appear in the stillbirth rates. In the United States there are State to State differences in reporting stillbirth. Although there is disagreement on the direct cause of death between studies, UCA is implicated with stillbirth.(28),(29),(30),(31),(32),(33) As of the year 2002, given the best evidence published, a rate of @ 2 deaths/1,000 births is due to an UCA. In the United States this would be 4,000 to 8,000 deaths per year of genetically normal fetuses. This is equivalent to the occurrence of death in genetically abnormal fetuses with congenital anomalies which is reported to be @ 2 deaths/1,000 births.(34 )(35 )

Another perspective is the spectrum of UCA stillbirth over the course of pregnancy: 60% prior to 20 weeks, 5% from 20-36 weeks and @15% from 36- 40 weeks.(36),(37) In practical terms, one out of every three to five deliveries will have an umbilical cord finding. One out of 100 deliveries will be at risk of an UCA stillbirth. Of the 2 UCA stillbirths /1,000 births, one will be premature and one will be a term stillbirth. For comparison, a significant shoulder dystocia with injury occurs in 1/1,000 births, a significant case of preeclamsia occurs 2/1000 births.(38),(39)

Some reports have difficulty relating fetal death to UCA. Pathologic evidence for UCA as the primary cause of death is not always apparent and confounding factors can present difficulty in determining a clear cause of death. A careful pathologic examination is indicated in all UCA related deaths. (40),(41),(42),(43),(44),(45) Two separate reviews of stillbirth studies looking at umbilical cord etiologies disagreed with the previous diagnosis of cause of fetal death. One review saw UCA as an etiology where there was none originally, the other saw confounding factors where UCA were the cause originally.(46),(47) There is evidence of UCA as a cause of death in mammals, especially horses. The pathologic markers for cord compression are well described in these veterinarian cases.(48),(49),(50),(51),(52) Small case studies have demonstrated evidence for umbilical cord involvement as the cause of fetal death in humans. In some reports the cause of umbilical cord disruption was not seen at delivery but shown by pathologic review. (53),(54) Also reported are maternal (55)(56), fetal (57) and iatrogenic induced injury to the umbilical cord with subsequent failure as the cause of injury or death.(58),(59),(60),(61),(62),(63),(64),(65),(66),(67),(68),(69), (70),(71),(72),(73),(74)

UCA can also repeat in the same patient. Reported cases have described subsequent pregnancies with similar UCA (Constriction, ELUC-excessively long umbilical cords) although not necessarily stillbirth. (75), (76) Cases collected by us (on file) have reported as many as 4 separate deliveries from the same mother, each with a true knot. It is not unusual for a nuchal cord to be repetitive in pregnancies from the same mother and family. It is not unusual to see similar patterns of UCA repeat from case to case. For instance, the pattern of most nuchal cords (>80%) are wrapped right to left around the fetal neck. Most torsion is (>70%) counterclockwise (sinestral, left-handed) away from the fetus. This suggests the fetus maneuvers in the same direction most of the time when stimulated. Is there an inherent reflex, similar to Moro's reflex which allows for this? The fetus can develop entanglement and escape from it. It is possible for a 20 week fetus with a triple nuchal cord to free itself of the loops by 28 weeks.(77),(78) Did the loops unwind or did they slip over the fetal body? Nuchal loops may slip over the fetal body as the most common form of escape from entanglement. Because in case reports these patterns are similar, it suggests UCA stillbirths are not random but due to specific intrauterine behavior of the fetus. These behaviors are limited in scope, just as a newborn is limited in its' movements. Because there are purposeful reasons for UCA, the same factors can lead to repeat events in the same mother. UCA can no longer be dispelled as random. Overall, stillbirth may be a statistically significant risk factor for subsequent pregnancies. There are no studies looking specifically at UCA associated stillbirth repetition.(15),(79),(80),(81) Table I lists the incidence of common UCA's in humans.

What umbilical cord fundamental factors might contribute to UCA?
Different characteristics in umbilical cord structure and function may predispose a given fetus to UCA under stressful conditions. Umbilical cord properties; tensile strength, diameter, circumference, Whartons jelly content, weight, and length, may be determined genetically. Umbilical cord development, differentiation, growth and elongation may depend on the sex of the fetus, its nutrition and well being. The anatomical connection of the umbilical cord to the fetus and placenta may be independent issues of growth, development and separation. The human umbilical cord varies in its microstructure and elemental content from arteries to vein. Variations in enzyme content exist from fetus to placenta. There are also biochemical differences in the umbilical cords of normal and abnormal fetuses.(82),(83),(84),(85),(86) Aberrations of the attachments can affect the function of the umbilical cord. These differences from fetus to fetus may explain the vulnerability of one fetus over another with a similar UCA (such as nuchal cord).

Tensile strength: Several reports have measured the breaking point of the human umbilical cord. Because of the differences among cords in Wharton's jelly, collagen content, and muscle layer structure there is a range of breakage points and sites.(87),(88) The average load required to break the majority of human umbilical cords is 10-14 lbs. The range being 4-24lbs (at term- 1.81-10.89 Kg). Cords ruptured 22.5% of the time at the placental end (without description of the attachment).(89),(90),(91) Umbilical cord traction forces of 8 lbs usually separated the placenta from the uterus. Otherwise most cord ruptures were within 12 inches of the fetus. The human umbilical cord is elastic and will stretch to 12.5% of its length. The tensile strength may average 2.5% of fetal weight . As a result some fetuses may tolerate more traction and loss of slack during entanglement than others.(92),(93),(94),(95)

Diameter/Circumference: The human umbilical cord has a reported average diameter of 1.5 cm and a separately reported average circumference of 3.6 cm after birth. The umbilical vein and artery have been measured before and after birth . The ultrasound average vein diameter is 8mm with an average artery diameter of 4 mm at term . (96),(97),(98),(99)

Wharton's Jelly content: Umbilical cords can be large (thick) and exceed an average of 4cm in circumference, especially at the umbilicus. The average weight is 15 gms/ 10 cm at term and dependent on male gender, prepregnancy maternal weight and birthweight .(8) Umbilical cord swellings at the attachment to the fetus should be examined before cutting and clamping the cord. The section may contain urachal elements, bowel, embryonic remnants or a vascular anomaly. Documentation of umbilical cord fetal end swellings should be made at delivery and edema noted.(100),(101),(102),(103) Umbilical cords can be lean (thin), < 1cm in circumference and lack Wharton's jelly. Postdates fetuses and IUGR fetuses are associated with lean cord appearances . This finding may suggest poor nutrition and lack of glycogen in fetal tissues.(584),(585) Alteration of umbilical cord water and molecular content may also play a role as an independent risk factor for poor outcomes.(104),(105),(106),(107) The average cross sectional area of the human umbilical cord is 14 sq/cm. Lean umbilical cords may be different in blood flow characteristics. They may also be more vulnerable to compression which requires Doppler studies of blood flow to determine whether or not there are compressed segments. Amniotic fluid content must also be normal before assessment of abnormal cords can be made. There are no studies comparing UCA in thick vs lean cords.(108),(109),(110),(584,(585)

Length : The human umbilical cord can be totally absent or reach a length of 300cm.(111),(112) Umbilical cord length is the only factor associated and documented as a definite risk factor for poor fetal outcome. There is an association of abnormal cord length with neurological abnormalities and low IQ values. A multivariate analysis of a small sample of pregnancies ( n 1087 births) reported an association with long cords and IUGR only. An evaluation of all umbilical cords for extremes of length and development should be considered at all deliveries at this time due to findings in larger studies.(113),(114),(115),(116),(117),(118)

Absent or Short (< 35cm) umbilical cords (@ 3% of cords) have been described and reported in cases of congenital anomalies. A short cord may be due to reduced fetal activity (such as with twinning; monoamniotic and conjoined), as a primary failure of elongation (genetic ?), and in association with Sirenomelia (lack of adequate fetal blood pressure), Shisis, Anencephaly (lack of hypothalamic hormones?), Acardia (cardiac output?) and adhesions (Early Amniotic Rupture Sequence -EARS). There may be additional factors involved in cord lengthening which are not tension related. Absolutely short cords can interfere with the mechanics of labor and delivery while exhibiting changes in fetal heart rate patterns. This restriction of decent (which is relative to the placental position and insertion) leads to an increase in the incidence of cesarean section ,forcep and vacuum extractions. Relatively short cords (lengths compromised by fetal entanglement causing loss of slack) can interfere with delivery as well.(119),(120),(121),(122),(123),(124),(125),(126), (127),(128),(129)

Long umbilical cords (>70CM @ 4% of cords) are documented to be directly associated with poor fetal outcome and associated with UCA especially; fetal entanglement, true knots, (sometimes multiple) and torsion. Placental changes are associated with long cords suggesting blood flow disruption or increased resistance.(130) Male cords are longer than female cords and term vertex fetuses may have longer lengths than term Breech fetuses (with the duration of presentation unknown). Multigravida cord length may be longer than primagravida cord length (the first pregnancy having a shorter length than the third , this may imply more room for movement-tension or more blood supply/hormone production/fetal-maternal weight gain). Twin gestations may have fetuses with discordant lengths and shorter lengths than singletons. Single umbilical artery vessel structure is increased in long cords. There are no studies considering maternal smoking, alcohol, caffeine, or cocaine ingestion and umbilical cord length in humans (animal studies report shorter cord lengths than controls).(131) Umbilical cord function is not readily impaired by longness and venous return from the placenta to the fetus is maintained regardless of length.(132),(133) There are no studies measuring the umbilical cord prenatally and evaluating the risk factor of cord length for poor fetal outcomes.(458),(134),(135),(136),(137)

Umbilical Cord vessel number: Reports of five vessels (153) ,four vessels, fused cords in twins and two vessel cords have associated fetal conditions. (138),(139),(140),(141),(142),(143),(144), (145)

Single Umbilical Artery (SUA) cases have been reported with a variety of genetic, anomalous and stillbirth outcomes.(146),(147),(148),(149),(150),(151)
There are no confirmed genetic associations with UCA to date. SUA is considered to be a developmental UCA associated with disturbance of fetal blood flow. There are two forms of SUA, a helical form and a straight form. (152) (see photos). Many observations have been published about this umbilical cord maldevelopment which is seen in @ 7% of abortises up to 28 weeks , @7% twins and occurs in @1% of term pregnancies.(153),(154) There may be an association between the left or right umbilical artery that is absent and increased risk of fetal abnormalities. There may be several categories of SUA depending on which vessel represents the umbilical artery (vitilline, allantoic, R or L umbilical).(9) There is also a difference in malformations depending on whether the right or left vein persists. (10),(155),(156),(157),(158),(159) SUA is associated with stillbirth with an incidence 3%-20%. SUA is common in twins, diabetic pregnancies, in association with long cords and small placentas. Finding an SUA on ultrasound screening should place the pregnancy on alert for associated developments.(160)
Umbilical Cord Vessel Morphology may be a risk factor for the fetus. The "normal umbilical cord" may have been best illustrated and described in 1882 by E S Tarnier (161). An arterial pair mildly helical around a straight vein. There are differences in umbilical cord shape which may predispose the fetus to UCA. There may be eight different types of umbilical cords.There are biochemical differences within the umbilical cord from placenta to fetus which are distinct and in compromised fetuses versus normal fetuses.(162),(163,(164),(165),(166) It is theorized that several factors may determine umbilical cord shape. Fetal cardiac output, predominance of umbilical artery blood flow, and fetal symmetry may be important.(521) Study by Doppler velocimetry of cord length, artery pairs and helical types have suggested some differences which may be important, but fetal outcomes were not always reported. There may be an inherent role of the umbilical cord to assist the fetal heart. If so, umbilical cord morphology may change this assist action or 'pulsometer'. Previous studies on UCA have not fully considered the differences which may be inherent in these different forms.
Table II lists the different umbilical cord forms.(132), (167),(168),(169),(170),(171),(172),(173), (174),(175),(176),(177),(178),(179),(180),(181)

Umbilical Cord Attachments: There is specialized anatomy for the umbilical cord attachment to the placenta and fetus.(182) Failure of these attachments will cause fetal death.(183),(184) The umbilical ring is designed to allow for fetal growth without umbilical cord detachment until delivery. The umbilical ring is innervated and these nerves have branches which connect to the vagus trunks and phrenic nerves. There are connecting branches to the right adrenal gland and maybe to the proximal umbilical cord . This neuronal pattern may suggest an umbilical ring to ductous venosous feedback system which partly regulates blood flow to the fetal cardiovascular system.(185),(186), (187),(188),(189),(190),(191),(192), (193),(194),(195),(196),(197),(198) Failure of proper umbilical cord development at the fetal attachment can cause stillbirth. As stated previously, absent umbilical cord syndrome is fatal. Other defects can be due to embryonic structures and remnants at the proximal cord. Proximal umbilical cysts, urachal anomalies and vitiline vessel anomalies have been well described in pathology texts. (8),(9),(10,(11) Periumbilical skin length may also have extremes of which long skin lengths have been noted in dysmorphic children and UCA in horses. (49: pg 602),(199)

Constriction is the narrowing of the umbilical stump attachment and is usually a cause of early stillbirth. Constriction should not be confused with Torsion (an UCA that can occur associated with constriction). Constriction may be caused by a variety of factors which eventually impede blood flow. Case reports provide the majority of insights into constriction which has not been prenatally diagnosed. Constriction does repeat in the same mother suggesting a genetic origin. From interviews, several verbal case histories have been documented of constriction stillbirth where one mother experienced four episodes in a row. (200),(201),(202),(203),(204) Placental attachments can be malformed and result in fetal morbidity and mortality (@ 10% of term placentas). IVF patients may be predisposed to placental attachment malformation.(205),(206),(207),(208) Marginal cord insertion (2.7%-15%), velamentous cord insertion including vasa previa (33%-12wks to 26.5%-16wks to 1.7%-11% 38wks) and furcate(1%?) insertion are susceptible to compression, torsion and rupture depending on intrauterine location. Abnormal placental attachment can affect fetal weight and may be detectable by 20 week ultrasound. Vasa Previa is at high risk for fetal demise especially with rupture of membranes (50% risk of death). The initial event of implantation of the fertilized egg may dictate the potential for the placental insertion outcome. Fetal heart rate screening may detect insertion compression by the fetus causing both tachycardia and bradycardia unresolved by patient repositioning. These observations at a prenatal visit might prompt an ultrasound review of placental location and umbilical cord placental insertion. A finding of a bilobed placenta or two vessel cord should also be suspicious for a velamentous cord insertion (12.55% have SUA).(209),(210), (211),(212),(213),(214),(216),(217) Studies are needed differentiating umbilical cord-placental insertion, placental location and fetal outcome.(218) The distribution of fundal located insertions from lateral, cervical, anterior and posterior are unknown. The occurrence of fetal compression risk based on cord insertion location is unknown.(219),(220),(221),(222)

UCA'S that are common. Keeping the before mentioned discussion in mind there are many variables which determine individual UCA. There are over 25 different types of UCA described in published medical literature. Since the CPP, information has accumulated which suggests that these events collectively are common. UCA occurs throughout gestation from conception to delivery with predispositions in each trimester. Table (I) lists the common UCA of which one is likely to be encountered every year by an obstetrical caregiver. Common UCA include Nuchal cord, torsion, true knot, body/extremity loops, velamentous insertion, marginal insertion, SUA, constriction, and prolapsed cord. A review of published literature to date regarding these UCA suggest they are important risk factors to be considered in preventing fetal morbidity and mortality.(223) By comparison, .1% of IUGR fetuses born at 38wks are at risk for stillbirth or 1 IUGR death/1000 births (224)

Torsion may be a common UCA. Stillbirth is associated with torsion and usually the cause of death is identified by the pathologist.(225),(226),(227) There is no definition of torsion published. It is a common cause of death in horses and is readily recognized by veterinarians as the cause of death (not a death artifact).(49),(228) Torsioned umbilical cords can be untwisted .(48) This is different from natural helixes which cannot be untwisted. In equine studies, a nonhelical umbilical cord is normal. Long straight equine umbilical cords tend to be twisted by the fourth month of gestation with an average of 3 twists. The twists can be removed by rotating the foal at birth. Intense twisting can cause urachal and vessel obstruction.(229),(230) These twists can cause umbilical blood flow obstruction if they exceed the ability of the cord to absorb the torque. Torque is absorbed by buckling or snarling "Hockling" as with a telephone receiver cord. (231),(235;Fig 6&7) If tension is applied, kinking results blocking blood flow. The incidence of torsion is unknown in liveborns. A prospective prenatal study of UCA's estimated torsion to occur in 10% of deliveries depending on a definition of 1 twist/ 9cm of cord length or less. The umbilical cord was "untwisted" at birth to its fundamental 6-8 helixes and twists compared to length.(19) A current study from China reported the occurrence of torsion to be 6.14% with a fetal death rate of 39.29%.(232),(233) This observation is not the same as a hyperhelical umbilical cord which is made up of helices which cannot be untwisted. The embryo develops 6-8 helices from @ 6-10 weeks when at that time it forms a physiologic umbilical hernia. "The characteristic helical structure of umbilical cord appears at an early stage of development and the basic pattern does not alter as pregnancy proceeds" to term.(234) Helices grow by increasing the "pitch" in between each vein/artery turn. As the umbilical cord lengthens the helices get further apart. Twisting brings the helices closer together (causing the pitch to shorten). The average length cord has 6-8 helices and 3 twists (or 11 coils/spirals/turns/curls).(235) This fact allows a determination of torsion in a liveborn. If the twists to cord length (without the helices) exceed 1 twist/ 9cm or less, torsion exists. Obviously this can not be determined until delivery, but it is an observation which should be documented as will be discussed. Umbilical cord torsion is associated with placental thrombosis, amniotic bands, and umbilical ring constriction.(11),(231),(236,(237),(238),(239),(240)

Nuchal Cord is a common UCA. Nuchal cord (which occurs @ 15% of deliveries) is separate from nuchal loops which by definition does not encircle the fetal neck (which also occurs @ 15%). Nuchal cord can be one encirclement to eight and has been reported in conjoined twins.(241),(242),(243),(244),(245)

There are two types of nuchal cord. Type A and Type B.(246),(247) The risk of fetal injury or death due to a nuchal cord is a difficult analysis when reviewing past literature. There are no prospective prenatal studies to determine fetal effects. One review of multiple nuchal loop cases could not detect an increase in fetal mortality. A review of fetuses with nuchal cord identified before 28wks could not detect an increase in poor outcomes. These studies may be incomplete and require larger cohort groups. If the fetal death rate due to nuchal cord alone is 1 death/2000 births, then a larger study with a no risk cohort is needed to determine risk factors of death. It may also be that multiple nuchal loops is not a risk factor so much as the specific situation where there is no slack. Umbilical cord compression occurs when there is loss of slack and tension is created on the UCA ( regardless of loop numbers ). Case reports of single and multiple loops of nuchal cord have documented fetal compromise prenatally. Metabolic studies have suggested fetal physiologic changes with nuchal cords. There are no studies comparing umbilical cord placental insertion, placental location, nuchal cord presence and fetal outcome. Without prenatal assessment, it would be difficult to identify at delivery a tight nuchal cord which was tight before labor. In an extensive study on neurologic injury and its association with nuchal cord, tightness was not identified prenatally.(248),(249),(250),(251),(252),(253), (254),(255),(256),(257),(258),(259),
(260),(261),(262),(263),(264),(265)

Body loops and Extremity loops may be more common than previously reported. Vaginal delivery mechanics undo these points of cord compression probably before they can be observed. Prenatal documentation of occult cord compression would be needed to accurately determine how often the fetus is affected. The CPP reported no ill effects from cord body part entanglement (BP- UCA) in singletons. The issue may be that these fetuses are stillborn before labor and are not accounted for as labor related UCA or stillbirths with BP-UCA. These cases in some senarios are not recognized after birth because the compressed cord loop or segment is undone by the mechanics of birth. Four published studies were identified reporting specifically on BP-UCA other than the CPP. One reported a Body Loop incidence of @ <0.5% with a 10% stillbirth rate. A prospective study using Doppler velocimetry, NST and imaging for body loops reported an occurrence of BP-UCA of 23.23% with a fetal distress rate of 85.29%.The cesarean section rate in this group was 88.28%.(266),(267),(268)
True Knot is a risk factor for the fetus. A recent large study placed the occurrence of true knot at 1.2% (841 knots/69,139 births).(269) A multivariate analysis found multiparity, chronic hypertension, hydramnios, nuchal cord and male gender associated with true knot of the umbilical cord. The CPP for comparison reported an occurrence of 1% in 55,908 births. The practical meaning of these statistics is a true knot will be encountered once or more each year by the obstetrical care giver. With a 1.7%-10% mortality risk in singletons, (>50% mortality risk in MAT), all true knots should be taken seriously. True knots are the result of Type B nuchal cords , and when considered as such ( 1 Type B NC/ 50 NC births) , the risk of fetal compromise is increased with this UCA. Any cord knotting discovered at delivery should be submitted with the placenta for pathologic review. Umbilical cord narrowing or placental villous changes are signs of chronic cord compression and may be important to document if there is associated fetal compromise. The risk of stillbirth is greater before labor (CPP 10x more risk) and can occur from 12wks to term. Cord knotting may occur as a result of delivery (a type B loop being pulled off its neck, waist, or extremity position). Knotting in singletons is a sequence of events which creates a loop of cord counter to the twist (torque) applied by fetal movements (which may be due to blood flow disturbances). This Hockle of umbilical cord is engaged by the fetus through activity and becomes a nuchal cord (type B hitch). This loop passes over the fetal body with time and creates a true knot. Double and complex knots are formed based on the number of turns in the hockle and number of hockles. A cord with a double turn hockle can become a double knot. Two hockles can become two knots at one passage of the fetus. These events probably take days to weeks. As with any cable or tubular structure, excessive torque will eventually cause collapse of the structure. Evidence of fetal heart rate changes, umbilical blood flow reduction, decreased fetal movement and fetal hiccup has been reported with cord knotting.(247),(270),(271),(272),(273),(274),(275),(276), (277),(278),(279),(280),(281),(282),(283),(284)

Umbilical cord prolapse and Funic presentation can occur from .5% to 1% of pregnancies . Breech presentation, twins, long umbilical cord and preterm birth are common associated risk factors. One large study reviewed 56,283 births and documented 132 cases of prolapse. Outcomes included six stillbirths, six neonatal deaths and one neurologic injury. This is similar to the CPP report in that neurologic morbidity was low. The CPP also reported a higher frequency of stillbirth. This may be due to the time to delivery was usually within 30 minutes in the reported large study. Fetal heart rate monitoring was "ominous" in 41% of cases and questionable in 16% of cases. One report on time to delivery suggests this may not be relevant. Funic presentation can be identified with ultrasound and cord compression during labor can be evaluated with Doppler velocimetry as an adjunct to fetal heart rate monitoring. Recommendations for reducing complications due to funic presentation and umbilical cord prolapse have been published.(285),(286),(287),(288),(289),(290),(291),(292), (293),(294),(295),(296)

Is there UCA morbidity ? In addition to mortality from UCA, there is also an issue of morbidity from UCA. The CPP noted UCA associated fetal effects such as; meconium, asphyxia, fetal growth disruption, and low IQ values.(297),(298),(299),(300),(301),(302) It is unknown to what extent the fetus is injured by umbilical cord blood flow changes in utero.(303) Since the CPP only two studies could be located addressing UCA morbidity directly.(304),(305) UCA's were related to prolonged second stage of labor, failure of decent of the presenting part ,postpartum bleeding, and fetal distress. A case report on failure of decent due to a nuchal cord and reports of consequences of tight nuchal cord illustrate the contribution of UCA to fetal morbidity.(306),(581) In human case reports UCA associated injuries documented are ; neurologic, cardiac, renal, pulmonary, gastrointestinal, hepatic, vestibular and ophthalmic. In one study, meconium and in another study, funisitis affected umbilical cord vessels (causing spasm?) leading to fetal ischemia and pulmonary injury.(246),(307),(308),(309),(310),(311),(312),(313),(314),(315),(316),(317),
(318),(319),(320),(321),(322),(323),(324),(325),(326)

Pathologic evidence of umbilical cord involvement in fetal injury that has been reported consists of : pleural petechiae, empty thymus, placental chorangiosis, placental vessel thrombi, umbilical cord edema ,obvious knot cinching with umbilical venous congestion, ruptured vessels due to velamentous formation, pulmonary debris from gasping and torsion with and without constriction and amniotic bands.(327),(328) There are published laboratory findings associated with UCA cases. Fetuses with a UCA will experience biochemical alterations in levels of ; ACTH/Cortisol, Erythropoiten, Triglycerides, Endothelin, WBC shifts, NRBC shifts, and urine electrolytes. (329) For asphyxia in general, organ damage may be more prevalent than previously suspected and occur in a predetermined sequence. (330),(331),(332),(333),(334) Animal study literature has accumulated which simulates a variety of fetal organ effects due to umbilical cord compression. As in humans , there are varying presentations depending on the time and duration of the stimulus along with the gestational age of the animal fetus. Prospective studies are needed examining fetuses born live with UCA and the potential associated morbidity.(334),(335),(336),(337),(338),(339),
(340),(341),(342),(343),(344)(345)(346)(347)

What clinical signs may help to evaluate a fetus at risk for UCA ?
To date there are relative risk factors identified associated with UCA; parity, age, birth weight, race and gender. There are no confirmed genetic predispositions with the possible exception of cord length. There are genetic syndromes associated with long and short umbilical cord formation which have been mentioned previously. There may be a predisposition to UCA in patients with in vitro fertilization as cited earlier. Umbilical cord structural extremes may lead to an increased risk of stillbirth. Umbilical cord thickness vs thinness may be protective vs vulnerable to compression and disturbance of blood flow. There may be risk of UCA associated stillbirth with cord length where excess length may predispose to cord compression. This may occur not only due to the absolute measurement of the cord but due to the relative amount of "slack". Therefore it does not matter for instance how many nuchal loops are present (one or five for example), but do the number of loops present create cord tension and compression. This lack of slack can lead to cord tension which may stimulate cord compression and umbilical artery spasm at the site of entanglement.(348),(349) Pathologic evidence for this has been noted in cases of skin grooving from cord entanglement.(10,Fig 5-14) Therefore if an umbilical cord is 45 cm long with a fundal placental insertion and the fetus has a nuchal cord, there may be a risk of nuchal cord compression depending on the fetal size. If the umbilical cord is 90 cm long attached to a low anterior placenta and there are 4 nuchal loops there may be enough slack so as not to create cord compression or restriction during labor. There may be an increased risk of stillbirth if the nuchal cord is looped vs hitched (Type A vs Type B- where type b forms knots once it slips over the fetal body) . Previous nuchal cord literature has not considered this detail. It takes a Type B nuchal cord to slip over the fetal body to form a knot. Once formed, it is not unusual to see case reports of a double nuchal cord and true knot at the fetal neck. The fetus rolled in response to the restricted circulation formed by the true knot. It developed 2 loops, created tension - lost slack and cinched the knot. An average 50 cm cord would only allow for 2 loops [10cm/loop-neck2x =20cm +10cm to umbilicus + 20cm to placental=50 cm]. There may be increased risk of UCA stillbirth when a combination of factors are present such as; thinness-marginal insertion-nuchal cord and true knot all in the same fetus. Finally, independent fetal behavior may play a risk/role such as hyperactivity (maybe with xanthines) vs hypoactivity (as with cocaine exposure leading to a short umbilical cord).

Hyperactivity is a fetal response associated with cord length risk factors. This fetal behavior may be related to intrauterine seizure or blood flow disturbance which may stimulate the fetus to react reflexly and excessively. Studies of animal models (rats, sheep) have reproduced forms of hyperactivity with cord compression. Hyperactivity may be a prenatal behavior capable of repositioning the fetus . In the rat model umbilical cord compression triggered lateral trunk curls, head tosses, and foreleg extensions. These movement patterns are uncharacteristic of normal spontaneous movements. (personal communication with Laura Bennet ; Liggins Institute),(350),(351),(352) A specific study of "excessive fetal activity" in humans did not detect poor fetal outcome and did not report on UCA risk. The fetal movements recorded may have been normal fetal behavior. Time of observation (bedtime and 12mn-6am) may need to be included in any future study.(353),(354) Fetal jerking movements and fetal hiccups may also be related to fetal blood flow disturbances especially cord compression. These maternal observations should be taken seriously.(355),(356),(357) Decreased fetal movement should be investigated with the objective to rule out umbilical cord entanglement and UCA especially in no risk patients.(358),(359),(360) Fetal breathing movements may be an indication of fetal well-being with gasping or absence of fetal breathing suggesting developing asphyxia.(361),(362),(363) Fetal heart rate detection prenatally should include a recording to document changes in baseline and FHR patterns associated with umbilical cord compression. Umbilical cord compression has varying effects on fetal physiology depending on the degree of the stimulus and a duration of the interruption of blood flow. Gestational age of the fetus also determines the response to umbilical blood flow changes. These fetal responses have been clearly described in animal models and human case reports.(364),(365),(366),(367) In lamb fetuses, repetitive intermittent cord compression ellicits a pattern of fetal heart rate responses which are V shaped, U shaped and W shaped in the early period of compensation. These changes are simultaneous with cord stimulation and due to chemoreceptor and baroreceptor responses (which are for quick fetal compensation). As the repeated stimulus continues, the fetal heart rate patterns form the more obvious variable deceleration appearance and eventually the late deceleration appearance. These patterns form based on late fetal compensation due to acidosis, peripheral vasoconstriction, increases in catacholamines, cortisol and various biochemical defenses. A 50% reduction in umbilical blood flow is necessary to stimulate the formation of these patterns.(368),(369),(370),(371),(372),(373) Similar fetal heart rate patterns are present in human fetuses with cord entanglement. W waves, Lambda waves, Spikes and slow recovery of variable decelerations have been documented in case reports. There are no studies quantifying the number of cord compression patterns over time and fetal outcomes.(374),(375),(376),(377),(378),(379),(380),(381),(382),(383),(384)

Observations by ultrasonography of fetal umbilical cord grasping provide another in vivo confirmation of fetal heart rate response. These case reports demonstrate the degree of cord compression needed to stimulate recognizable patterns similar to those seen in fetal sheep.(385),(386),(387),(388)

Fetal Heart Rate Monitoring remains a controversial means of evaluating fetal well-being. (389),(390),(391) A review of Non Stress Test (NST) studies concluded that, "NST is a relatively good predictor of adverse outcome when morbidities and moralities are combined". This review did not specifically analyze UCA related NST.(392) Fetal heart rate normalcy has been reported which allows comparison of UCA influenced FHR patterns. Umbilical cord compression patterns are described previously which differ from normal.(393),(394),(395),(396) Studies specifically evaluating UCA and screening by means of NST and or OCT have been few.(397) A recent evaluation of NST to detect UCA's relied on the classic variable deceleration pattern. In a double blind study design, NST could not be demonstrated as a reliable screen test in half of the 50 UCA cases. In a review of 2000 NSTs , 46% had decelerations in response to fetal activity. Because 3 deaths occurred due to abnormal cord position, it was concluded that this FHR pattern be evaluated with ultrasound and OCT for cord compression. A similar study of decelerations with fetal movement noted the additional association with small for gestational age fetuses and the likelihood of abnormal cord position. The SGA group with cord compression decelerations had an increase risk of cesarean section.(398),(399),(400) Another study reviewing a large cohort reported an accuracy of 76% in predicting cord compression from a NST. One study which used V wave,U wave and W wave as the key determinate reported NST could be a useful test especially if done with an CST. (401),(402) Cases of cord entanglement in humans, studied by observing the cardiac electromechanical interval PEP (prolonged ejection period), noted the PEP to be prolonged. In animal models (sheep,baboon), EKG analysis noted T QRS changes and PR interval changes with cord compression. Atrioventricular block with extrasystolies have been noted with umbilical cord compression.(128),(403),(404),(405),(406),(407),(408),(409),(410),(411),(412) These observations illustrate that there is an effect on the fetal heart when umbilical blood flow is altered. At this time the clinical relevance is that a tool is available to detect UCA .What is needed is a means to gage the UCA impact on the fetus (413),(414)

Umbilical Cord Compression has been studied under controlled laboratory conditions. There are numerous animal models which suggest chronic , intermittent, and acute umbilical cord compression cause specific fetal physiologic responses over time. Computer modeling of the fetal placental circulation has aided our understanding of this unique circulatory system.(415),(416),(417),(418),(419) Interruption of umbilical blood flow greater than 50% is significant for creating fetal hypoxia. Sustained and or repetitive compression eventually leads to fetal compromise.(420) Occlusion of the uterine artery has similar effects on the fetus with specific differences on the fetal heart and brain. Combined umbilical cord occlusion and uterine artery occlusion has effects on fetal organs and metabolism .(421),(422),(423),(424),(425) The physiologic model for prenatal umbilical cord compression is that the fetus once it has developed a UCA is compromised. Cord compression; whether chronic, intermittent or acute, ultimately stimulates the fetus to shunt its blood flow, vasoconstrict its extremities and protect itself through a centralized circulation (heart,adrenal,brain). The initial sensor in detecting blood flow interruption is the umbilical ring (as previously described). The next physiologic mechanism affected by changes in umbilical vein blood flow is at the ductous venosus (dv). The dv changes its shape to stream oxygenated blood to the fetal heart. Because it is innervated, it may also send neurologic responses to the brain.(426),(427) Baroreceptor and chemoreceptor responses occur with release of catacholamines, cortisol, vasopressin ,angiotenson and other biochemical agents to initiate a fetal response to developing hypoxia. Fetal metabolism of glucose and gluconeogenesis are induced by cord compression. Arterial lactate elevations may be a measurable result of umbilical cord compression.(428),(429)

These protective steps over time can give way to bradycardia, vasodilation of the carcass, fetal hypotension, acidosis, depletion of glycogen stores and blunting of the cortisol response. Eventually fetal compensation will fail, peripheral vasodilation will occur with heart failure, arrhythmias and fetal death. These insights suggest that return of the fetal heart rate to a reassuring pattern after intermittent decelerations, that the biochemistry of the fetus is not restored immediately to normal or reassuring.(430) Short term rapid biochemical defenses such as catacholamines, are replaced by long-term endocrine and paracrine biochemistry . These agents are metabolized at a slower rate eventually leading to devastating fetal effects . In an intermittent cord compression sheep model with term fetuses (1 complete occlusion every 5 min),fetal collapse occurs in 45min to one hour . In a model of 5 min complete cord compression repeated every 30 minutes the fetuses died after 3 or 4 occlusions.(431),(432),(433),(434),(435)- This process is different from chronic asphyxia with placental insufficiency, fetal anemia, or fetal infection. The question is, how does umbilical cord compression happen in utero and when does cord compression occur prenatally to the degree simulated in the animal models? (436),(437) There are human case reports and studies which correlate with these animal model observations. There are human case examples which are well known for acute and chronic asphyxia due to cord compression such as: prolapsed umbilical cord, vasa previa rupture, or monoamniotic twin entanglement. Clinical signs which may be present given the biochemical status of the fetus at risk of umbilical cord compression compensation are; Hiccups, Hyperactivity, Decreased fetal movement and Fetal heart rate changes. Normal physiologic hiccups last < 5-10 min (especially after 32 wks). Cord compression hiccups, stimulating the ductous venosous, last > 10-15 min and occur > 4X / 24 hrs. Hyperactivity (especially during maternal sleep) may signify uterine ischemia, Decreased movement >50% may imply a centralized fetal circulation, Fetal heart rate baseline elevations > 150 bpm, Fetal heart rate bradycardia >100bpm may signal early fetal acidosis. Umbilical cord compression patterns frequently repeating on a NST ( such as W sign, Lambda sign , Spikes and possibly PAC's) should be investigated. These patterns are due to cord compression and are very distinct on NSTs. (438),(439),(440)
Identification of UCA with Ultrasound

Numerous published reports have identified umbilical cord morphology and abnormalities with ultrasound.(441),(442),(443),(444),(445),(446) Real time black and white ultrasound is able to evaluate umbilical cord structural abnormalities.(447),(448),(449),(450),(451),(452),(453),(454) Individual case reports have accumulated which demonstrate the ability of prenatal ultrasound to study the human umbilical cord , see Table III . (455-517)

The placental umbilical cord insertion site can be studied with black and white ultrasound.(518),(519) Umbilical cord blood flow can be studied with Color Doppler velocimetry techniques.(520) Doppler velocimetry has demonstrated alterations in blood flow with nuchal cords, true knots, single umbilical arteries and in fetuses with underdevelopment and cardiac failure .(521),(522) Because of these advances, recent articles have recommended prenatal review of the umbilical cord.(269),(523),(524),(525) One article recommends a prospective observational study.(526)

Can UCA be managed once detected by fetal monitoring and or prenatal ultrasound? Can UCA management prevent stillbirth and what studies in humans validate this? To date case reports suggest UCA can be identified and managed.

For example, Monoamniotic twins (MAT) have a 70% or more risk of cord entanglement. These cases have been prenatally diagnosed with a variety of umbilical cord complications which can have 10% mortality if managed, to a 70% mortality if unmanaged. Several cases of monoamniotic triplets has been reported managed for cord entanglement complications.(527),(528),(529),(530),(531) This experience of fetal injury and loss has stimulated development of monoamniotic twin case management for UCA. In a study comparing managed MAT with published case histories of unmanaged MAT there was an improvement in perinatal survival of 92%. Thirteen case sets with a control group of seventy seven case sets (without prenatal diagnosis) showed a 71% reduction in the relative risk of perinatal mortality in the study group.(532),(533),(534),(535),(536),(537) In one case report, cord entanglement was originally diagnosed at 20 weeks. Amnioreduction was instituted to control fetal movements and diminish the risk of complications. Another similar report achieved diagnosis of MAT-UCA at 10 to 18 weeks and followed prenatally with ultrasound and NST.(538),(539) Evaluation of MAT with Doppler studies have detected cord compression and changes in umbilical blood flow. An umbilical artery waveform notch was observed in one report as an indicator of cord compression.(540),(541),(542),(543),(544),(545) (546),(547), (548), (549), (550)

These MAT studies and case reports provide the best evidence of fetal effects from UCA . It is possible to identify UCA with ultrasound in the first trimester. It is possible to follow umbilical cord blood flow with Doppler velocimetry. Its is feasible to monitor fetal well-being with fetal movement awareness, NST, and biophysical profile when UCA is present. Finally, there is evidence that fetal morbidity and mortality can be reduced when UCA is managed in MAT. What is needed is a prospective study in MATs and singletons.
Single umbilical artery can be identified with ultrasound , characterized and managed prenatally. Evaluation of fetal anatomy and umbilical blood flow can help determine fetal well-being.(465 Fukada)(551),(552)
Nuchal cord made up of single or multiple loops and umbilical cord Torsion have been prenatally identified and managed with liveborn deliveries (251),(252),(253),(311),(553),(554),(555)
Evidence of NST changes, especially cord compression patterns, can identify a fetus at risk of blood flow disturbances. True knot has been prenatally identified with ultrasound and managed based on fetal heart rate tachycardia and decreased fetal movement.(381),(481),(483),(556),(557) Funic presentation has been identified prenatally with ultrasound along with Prolapsed umbilical cord and managed with fetal monitoring allowing for uncomplicated delivery of the fetus. (478),(285),(291) Velamentous insertion and Vasa previa have been reported prenatally identified and managed successfully.(469),(476),(558),(559), (560),(561),(562),(563),(564) Umbilical cord length can be determined by ultrasound and the evaluation and management of long and short cords is possible.(126),(458). Fourteen cases of umbilical cord hemangiomas have been reported, prenatally diagnosed and managed.(501) Cases of Body loop and Extremity entanglement have been prenatally identified and managed during labor.(267),(268) Reported retrospective studies on various specific UCA's had poor identification rates because the UCA's were not being sought at the time of the ultrasound exam.(565),(566) Two prospective observational study in humans have been published investigating prenatal diagnosis and management of UCA in a low risk cohort of pregnancies. The results of these studies suggest it is possible to identify UCA prenatally and manage it.(268),(19) The results of these studies and case reports do not validate prevention of stillbirth due to management of UCA in singletons but does suggest it may be possible as with UCA managed MAT.

Can the risk of UCA be predetermined and prevented.
It is unknown what genetic or physiologic factors directly predispose the fetus to UCA. Possibilities are ; maternal effects, placental location, umbilical cord insertion, umbilical cord structure and morphology, and umbilical cord length relative to fetal dimensions, are variables to be considered.(567) Maternal side uterine blood flow restriction such as uterine ischemia may lead to the risk of fetal asphyxia over time. Milestones of supply and demand may not be met by the mothers vasculature relative to the fetus or under stressful conditions.(568) Maternal disease, as seen with cardiovascular disease in pregnancy, can interfere with fetal blood flow.(569) Further support for this concept is found in supine hypotesive syndrome (Posiero effect).(31),(570). Uterine ischemia may be a predisposing maternal factor leading to UCA and stillbirth. This may be an important issue throughout gestation. Fertility patients are known in some cases to have impaired uterine blood flow.(571),(572) It may be that over time, milestones of supply and demand are not met due to uterine blood flow restriction. (573),(574) Fetal heart rate decelerations are known to occur during maternal hypotension impaired circulation. Is there an association between maternal hypotension and stillbirth in the third trimester?(575),(576),(577),(578),(579) A review of the CPP database for hypotension and poor outcomes did not uncover an obvious effect. A small significant effect, <5%, may be present and more specific review of stillbirth cases between 36-38 weeks is being considered. (580),(581) Another unknown element is maternal hypotension, especially during maternal sleep. There may be a synergistic effect between maternal sleep, Posiero effect, a fall in fetal cortisol production, and uterine ischemia, all of which may be detrimental to the fetus . The fetal response to uterine ischemia at 3 a.m. may be hyperactivity to stimulate maternal movement and increased uterine blood flow. This fetal repositioning may lead to cord compression and or entanglement. Continuation of the sequence each night may combine with Braxton Hicks contractions or prolonged contractures due to uterine ischemia, to create fetal stress. The fetus that could not compensate to the extremes (between 36-38wks) may result in stillbirth. With these factors in mind, management of UCA requires an awareness of possibilities as there are few absolute facts at this time. Patients who report hyperactivity, especially during maternal sleep could have at least a NST .(582),(583) A persistence of unusual fetal movements, whether hyperactive or hypoactive, or fetal hiccups (on a daily basis) could include an ultrasound study to specifically look for cord compression or UCA. If a site of cord compression or UCA is seen , the patient could be informed to be aware of the fetal diurnal rhythm of movement and report any change which is uncharacteristic. If necessary, the patient could be admitted for observation and maternal-fetal monitoring overnight. Special attention should be given to maternal vital signs every hour and fetal heart rate patterns during 2-4 a.m. Presence of a non-reassuring fetal heart rate should lead to current obstetrical practices being followed. Ultrasound identification of UCA is possible and follow up of these fetuses requires current obstetrical practices of NST, Biophysical profile , and induction when indicated. Special attention during labor and delivery may help avoid an unexpected UCA adverse event in an otherwise normal pregnancy.(584)

Summary

The practical goal of 21st Century Obstetrics is not only to successfully deliver an infant but to do so without a poor outcome. This includes the best possible start in life mentally and physically.(441),(585) SADS ( sudden antenatal death syndrome, which accounts for @ 30,000 fetal deaths a year) is an important national health policy issue. UCA is a type of SADS which can be detected with ultrasound and can be managed with already established obstetrical practices. There may be UCA morbidity present in liveborns where previously unexpected. The interval from 36-38 weeks may require more scrutiny of the fetus, especially where a UCA is identified. Once more information is known about UCA, it may ultimately be recommended to consider delivery of the fetus at term and not manage the UCA associated fetus postdates. There may be a synergistic effect between maternal hypotension-uterine contracture-fetal cortisol-between 2-4 am and umbilical cord compression putting the fetus at risk for injury or unexplained stillbirth. A complete autopsy and placental-umbilical cord study should be considered when a UCA stillbirth is encountered. Evaluating all births with a placental-umbilical cord review may be cost prohibitive, but all stillbirths should be considered for pathologic review if the answers to unexplained stillbirth and direct cause of death are to be discovered.(586),(587),(588),(589) Research efforts should be encouraged into the study of stillbirth due to SADS and Umbilical Cord Accidents.(590) Well designed prospective studies are needed to evaluate the ability of ultrasound to consistently identify UCA. Management of prenatally diagnosed UCA and determination of fetal intervention, will create the ability to avoid stillbirth.(591),(592) Possible risk factors such as maternal hypotension need review. Finally the effects of UCA stillbirth on the family is significant. Care and support for the whole family is required and a suitable explanation of cause of death is needed .(593),(594),(595),(596) "Women want to be informed and have high expectations about the safety of their unborn child".(12)

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