Reference values for umbilical cord diameters in placenta specimens

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Reference values for umbilical cord diameters in
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placenta specimens
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H. Pinar1, Murat Iyigün2
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Halit Pinar, MD
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Brown Medical School
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Women and Infants Hospital
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Division of Perinatal Pathology
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101 Dudley Street
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Providence, Rhode Island 02905
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Murat Iyigün, PhD
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University of Colorado
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Department of Economics
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Boulder, CO
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Corresponding Author:
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Halit Pinar, MD
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Division of Perinatal and Pediatric Pathology
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Brown Medical School-Women and Infants Hospital
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101 Dudley Street
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Providence, RI, 02905
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Phone: (401) 274-1122 1190
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Fax: (401) 453-7681
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[email protected]
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Running Title: reference values for umbilical cord diameters in placenta
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specimens
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Abstract
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Context
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To determine the normal values for umbilical cord diameters in placenta
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specimens.
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Methods
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We retrospectively collected values of umbilical cord diameters from 973
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placenta specimens examined in the Division of Perinatal Pathology at Brown
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University. The specimens were examined using the same standard protocol
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during the calendar years 2005 t0 2007. Gestational ages of the newborns ranged
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from 20-41 weeks. Placentas originated from pregnancies associated with any
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condition known to cause fetal growth impairment were excluded. In addition,
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cases without complete clinical or pathological information and samples from
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multifetal gestation, or with developmental abnormalities such as umbilical cord
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masses were also excluded. The longest diameter of umbilical cords
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representative of the entire sample was measured and recorded. Since only cord
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segment(s) close to the placental insertion site were received in the laboratory, the
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measurements were obtained from these samples. No measurements were
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available from the remainder of the cords left with the newborns. To establish the
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link between umbilical cord diameters and gestational age, polynomial regression
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analysis was conducted.
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Results
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Measurements from 973 singleton placentas were used in the statistical
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estimates and distribution of normal values throughout gestation was calculated.
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The regression equation was y = - 11.9994 + 1.33966x - .018231x2 where y
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denotes the umbilical cord diameter in millimeters and x is gestational age in
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weeks. A statistically significant non-linear relationship was found between
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umbilical cord diameters and gestational age. The direct measurements of
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umbilical cords during the pathological examination were smaller than the
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ultrasound measurements by 30-40% over the gestational age range of 20 to 41
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weeks.
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Conclusions
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Reference values for umbilical cord diameters in placenta specimens were
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determined and their distribution according to gestational ages was calculated.
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Our nomograms are novel and derived from the pathological specimens rather
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than in vivo ultrasound examinations. Therefore, instead of published reference
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values of umbilical cord thickness in the pathology literature, which reflect in vivo
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ultrasound measurements, we recommend that the values collected from placental
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specimens should be used.
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Introduction
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Ultrasonographic evaluation of the fetus is very significant in the obstetrical
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management. In addition to fetal parameters it includes placental measures such
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as umbilical cord length, diameter, and degree coiling among others [1-8]. The
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values obtained in the ultrasonographic evaluation are compared with normal
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reference values allowing certain diagnoses. For example thin umbilical cords
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have been associated with fetal growth impairment. A study comparing growth-
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restricted fetuses with an appropriate for gestational age group has shown that the
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cross-sectional area of all components of the umbilical cord is reduced in the
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former [9-10]. In pregnancies complicated by early pre-eclampsia, the cross-
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sectional areas of the Wharton jelly and umbilical vein were found to be reduced
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in comparison to normal pregnancies [11-13]. An increase in the umbilical cord
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diameter has been described in pregnancies complicated by gestational diabetes,
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various causes of macrosomia and aneuploidies [7, 14-15].
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Evaluation of the umbilical cord is also an essential part of the pathological
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examination of the placenta. Proper macroscopic examination technique includes
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measurement of the length and diameter of the umbilical cord among other
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features [16-21]. Although most of the normal reference values for placental
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parameters were derived from pathological samples, umbilical cord diameter was
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not [19-21]. They have been derived from various studies that used
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ultrasonography in ongoing pregnancies [18-21]. Umbilical cords in vivo are
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active vascular conduits connecting the placenta to the fetus and
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hemodynamically active. Measurements obtained in vivo reflect active blood flow
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in the umbilical vessels. Blood flow keeps the vessels patent and prevents them
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from collapse. After delivery, blood flow ceases and the vessels constrict and
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collapse. These changes affect the shape and dimensions of the umbilical cord.
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The purpose of this study was to define the reference values of umbilical cord
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diameters between 20 and 41 weeks gestational ages using placental samples.
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Materials and method
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Population
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We retrospectively reviewed 5,499 placenta specimens that were examined
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during the years 2005-2006 using the same standard protocol by the Division of
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Perinatal Pathology at Brown University. Medical records were reviewed for
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demographic characteristics, maternal antepartum history and associated
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complications, birth data and neonatal findings. The pathology records of the
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placenta specimens were also examined and data extracted.
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Inclusion and exclusion criteria
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The criteria for placental examination at Women and Infants Hospital include
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similar conditions to the College of American Pathologists (CAP)
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recommendations (Table 1) [17]. Since our objective was to collect a cohort as
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normal as possible, any sample from a mother with any condition that has been
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associated with fetal or placental growth impairment has been excluded from the
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study. In addition, cases without complete clinical or pathological information and
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samples from multifetal gestation, or with developmental abnormalities such as
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umbilical cord masses were also excluded. Since placentas from term and
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uncomplicated pregnancies routinely were not sent to the Laboratory to be
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examined, 503 term placentas were randomly chosen and records reviewed. 372
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of these placentas were included in the study.
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Macroscopic examination of the placenta
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Placentas were examined fresh using a standard method. After inspection, the
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umbilical cords were trimmed leaving a stump at the insertion site measuring 0.5-
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1 cm. Next, the membranes were examined and trimmed. The trimmed placental
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disc was weighed after draining all the blood. The longest and shortest diameters
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of the placental disc were measured. After the placental disc was sliced into 1 cm
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thick slices, thickest and thinnest slices were measured.
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Measuring and sampling of the umbilical cords
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The length of all the received cord segments was measured. The umbilical
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cord segment closer to the insertion site to the placental disc was designated as the
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placental end (proximal end). The opposite segment towards the fetus was
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designated as the fetal end (distal end). Only the segments of the umbilical cords
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close to the placental insertion site (proximal) were available for examination.
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Irrespective of the shape of the cross section, the longest diameter representative
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of the entire umbilical cord sample was measured and recorded (Fig. 1).
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Data Analysis
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Data were collected into a central database and analyzed using Stata Version
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9.2 (2006, StataCorp LP, College Station, TX). We derived our baseline estimates
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using a non-linear (polynomial) Ordinary Least Square regression (OLS). We
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included gestational age as the main explanatory variable (x) and umbilical cord
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diameter measures as the dependent variable (y). We allowed gestational age to
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enter the empirical specifications non-linearly (i.e., we included x2 as a separate
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explanatory variable). This is done to capture a potentially non-linear relationship
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between gestational age and umbilical cord diameter, whereby the growth rate in
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the umbilical diameter can vary over gestational time. The distribution of the data
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by gestational age is summarized in Table 2. As shown, the average umbilical
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cord diameters peak during the 37th week and then drop somewhat in the
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remaining four weeks.
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Results
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During the study period, a total of 5, 499 placenta specimens were examined
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between 20 and 41 weeks of gestation. 973 (17.7%) specimens met the inclusion
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criteria. Maternal ages ranged from 18-49 years, whereas the median parity was
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two, ranging from zero to five. In all the 973 cases included in the study,
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estimated date of confinement was determined based on an accurate last
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menstrual period and confirmed by a first- or second-trimester sonogram. The
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gestational ages ranged between 20 and 41 weeks.
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Regressing the umbilical cord diameter (y) on gestational age (x) in a non-
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linear polynomial OLS equation produced y = - 11.889 + 1.352x - .01888x2 and a
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fit measure of R2 = 0.172. All variables yielded statistical significance with the
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intercept term -11.889 yielding P < 0.0001, the coefficient 1.352 on gestation age
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(x) producing P < 0.0001 and the coefficient of -0.01888 on the squared value of
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gestational age (x2) generating P < 0.002. The 5th, 95th percentile bands as well as
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the fitted mean values of umbilical cord measures that the regression equation
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produced are depicted in Figure 3.
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Discussion
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The umbilical cord serves an essential role in fetal intrauterine survival, but
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for a long period of time, it was one of the least studied components of the fetal
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anatomy during an ultrasound examination [1-2]. Prenatal morphological
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assessment of the umbilical cord is usually limited to the evaluation of the number
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of umbilical cord vessels. Other morphometric umbilical cord parameters, such as
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cord thickness and the amount of Wharton's substance or umbilical cord coiling
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have been reported but not routinely used [11-12, 22].
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Weissman and colleagues conducted the first study constructing nomograms
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for the umbilical cord components using ultrasound [2]. The authors established
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reference measures for the diameters of the umbilical cord, vein, and arteries. In a
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more recent study Raio et al. published nomograms of the umbilical cord diameter
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and area according to gestational age from 10 to 42 weeks of gestation [1]. In
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their study, umbilical cords were evaluated at the level of the umbilical cord
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insertion on 557 patients. They demonstrated an increase in umbilical cord
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thickness as a function of gestational age up to 34 weeks of gestation, followed by
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a reduction of this parameter. These findings were similar to the nomogram
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published by Weissman except the cessation of cord thickness in the latter study
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was observed later after 36 weeks [2].
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We replicated the findings of Raio et al., which are shown in Figure 4 [1].
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Based on a sample of 557 patients and gestational age range of 10 weeks to 41
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weeks, the Raio et al. study generated y = - 10.0563 + 1.4265x - .0194x2 with
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umbilical cord diameter as the dependent variable, y, and gestational age and its
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square as the explanatory variables (x and x2). In Figure 5, we compare Raio, et
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al.’s findings with ours. As shown, there is considerable similarity between the
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two results generated with the in vitro direct measurement of the umbilical cord
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and in vivo measurements obtained by ultrasonography which form the basis of
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the Raio et al. data [1]. We found a statistically significant non-linear relationship
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between umbilical cord diameters and gestational age. But the direct
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measurements of umbilical cords during the pathological examination were
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smaller than the ultrasound measurements by 30-40% over the gestational age
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range of 20 to 41 weeks.
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Although evaluation of the umbilical cord has been part of every
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recommendation on pathological examination of the placental specimens,
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reference values for umbilical cord diameters applicable to pathological
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specimens are not currently available. The sources of the nomograms in the
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published pathology literature are from ultrasound studies obtained in ongoing
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pregnancies. Since after delivery the fetal circulation ceases through the umbilical
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cord, the shape and measurements of this conduit changes. Thus they are not
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compatible [17-21].
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In this study, we determined the reference values for average umbilical cord
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diameters in placenta specimens and their distribution according to gestational
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ages. Our nomogram is the first derived from the placental specimens rather than
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in vivo ultrasound examinations. Since the published reference values of umbilical
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cord thickness in the pathology literature reflect in vivo ultrasound measurements,
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they are not appropriate. We recommend the use of the new values during the
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pathologic examinations.
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References
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Raio L, Ghezzi F, Di Naro E, Gomez R, Franchi M, Mazor M and Brühwiler
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H. Sonographic measurement of the umbilical cord and fetal anthropometric
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parameters. Eur J Obstet Gynecol Reprod Biol. 1999;83(2):131-5.
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Weissman A, Jakobi P, Bronshtein M, Goldstein I. Sonographic
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measurements of the umbilical cord and vessels during normal pregnancies. J
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Ultrasound Med. 1994;13(1):11-4.
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Sherer DM, Anyaegbunam A. Prenatal ultrasonographic morphologic
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assessment of the umbilical cord: a review. Part I. Gynecol Surv.
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1997;52(8):506-14.
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de Laat MW, Franx A, van Alderen ED, Nikkels PG, Visser GH. The
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umbilical coiling index, a review of the literature. J Matern Fetal Neonatal
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Med. 2005;17(2):93-100.
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de Laat MW, Franx A, Bots ML, Visser GH, Nikkels PG. Umbilical coiling
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index in normal and complicated pregnancies. Obstet Gynecol.
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de Laat MW, van Alderen ED, Franx A, Visser GH, Bots ML, Nikkels PG.
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Predanic M, Perni SC, Chasen S, Chervenak FA. Fetal aneuploidy and
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Predanic M, Perni SC, Chasen ST. The umbilical cord thickness measured at
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18-23 weeks of gestational age. J Matern Fetal Neonatal Med.
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Raio L, Ghezzi F, Di Naro E, Franchi M, Maymon E, Mueller MD,
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Brühwiler H. Prenatal diagnosis of a lean umbilical cord: a simple marker for
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the fetus at risk of being small for gestational age at birth. Ultrasound Obstet
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Gynecol. 1999B;13(3):176-80.
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10. Raio L, Ghezzi F, Di Naro E, Duwe DG, Cromi A, Schneider H. Umbilical
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intrauterine growth-restricted fetuses. J Ultrasound Med 2003;22:1341–7.
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11. Prabhcharan G, Jarjoura D. Wharton’s jelly in the umbilical cord. A study of
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its quantitative variations and clinical correlates. J Reprod Med 1993;38:612–
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12. Ghezzi F, Raio L, Di Naro E, Franchi M, Balestredi D, D'Addario V.
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Nomogram of Wharton's jelly as depicted in the sonographic cross section of
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the umbilical cord. Ultrasound Obstet Gynecol 2001;18:121–5.
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sonographic umbilical cord morphometry in early-onset preeclampsia. Obstet
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Gynecol 2002;100:311–6.
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Table 1 Indications of placental examination at Women & Infants Hospital of Rhode Island
Placental indications
Macroscopic abnormality of the placenta, membranes, or cord noted by U/S or at the delivery
Abruptio placenta
Retained placenta
Suspected small or large placenta
Suspected short or long cord (indicate on requisition length of cord that we will not receive)
Maternal indications
Systemic disorders with clinical concerns for mother or infant
Diabetes during any portion of pregnancy
Hypertensive disorders
Autoimmune disorders
Hematologic disorders
Seizures
Premature delivery
Delivery at ≥42 weeks
Oligohydramnios or polyhydramnios
Peripartum fever and/or infection
Clinical concern for infection during gestation
– Viruses, including HIV
– Bacteria, including Mycobacteria
– Fungi
– Parasites, etc.
Prolonged (≥18 hrs) and/or premature rupture of membranes
Heavy or repetitive bleeding other than minor first trimester spotting
Abruption
Intrauterine invasive procedures with suspected placental, umbilical cord or fetal injury
Current known substance abuse or positive drug screen
Severe trauma
FETAL/NEONATAL INDICATIONS
Fetal or perinatal death
Fetal or neonatal congenital anomalies, known or suspected
Compromised clinical conditions similar but not limited to the following examples:
Cord blood ph <7.0
Apgar scores <6 at 5 minutes
Ventilatory assistance >10 minutes
Anemia - Hct <35%
Hydrops fetalis
Seizures, persistent hypotonia, and hypoxic-ischemic encephalopathy
Infections, known or suspected
Intrauterine growth retardation or macrosomia (>4500 g for term infants)
Multiple gestation, including vanishing twin
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Prematurity 34 weeks or postmaturity weeks
Hematologic disorders as defined by:
– Anemia of any cause
– Erythroblastosis of any cause
– Hemoglobinopathies
– Thrombocytopenia of any cause
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