Abstract
BACKGROUND:
One key factor proven to increase quality of pregnancy outcome has been antenatal care (ANC) service. The perinatal triad of mother, placenta and fetus becomes functionally complete with a functional umbilical cord. The objective of the study was to establish mathematical models to predict the outcome of umbilical cord morphometric parameters using maternal first antenatal care visit biometric indices.
METHOD:
This analytical descriptive cross-sectional study was conducted on 240 pregnant women who attended antenatal care for the first time in their first trimester at the Victory Maternity Home and Clinic in the Kumasi Metropolis, between April 2016 and October 2019. Umbilical cord length, diameter, area, volume and weight were measured after delivery. Maternal first antenatal care visit blood pressure was taken and their non-fasting blood samples were collected and lipid profile done.
RESULTS:
Mean values for umbilical cord measurements were; cord length, 38.10±7.86 cm; diameter, 1.04±0.17 cm; area, 66.10±24.49 cm2 and volume was 34.02±11.16 cm3 respectively while mean cord weight was 65.01±21.35 g. The study found that a unit increase in total cholesterol led to an increase of 2.33 units in umbilical cord length, high-density lipoprotein also resulted in 0.06 units increase in cord diameter while low-density lipoprotein decreases cord length by 3.31 units. Also, a unit increase in maternal booking total cholesterol resulted in 2.33 units increase in umbilical cord length.
CONCLUSION:
Maternal first antenatal care visit total cholesterol, high-density lipoprotein and low-density lipoprotein could influence the outcome of umbilical cord length, diameter and area.
Keywords
Introduction
Antenatal care (ANC) is an important part of the Safe Motherhood Program that involves provision systematic medical attention to the pregnant woman during pregnancy till child birth [1]. One key factor proven to increase quality of pregnancy outcome has been antenatal care service [2]. According to a study, the first visit of a pregnant woman to the maternity unit of a hospital, clinic or health center is described as booking visit (BV). It happens to be the first encounter with healthcare providers as well as being introduced to the maternity services [3]. The perinatal triad of mother, placenta and fetus becomes functionally complete with a functional umbilical cord which offers a smooth passage of blood from the placenta to the fetus or fetus to placenta. The umbilical cord is morphologically composed of two arteries and a vein embedded in a nutrient –rich substance referred to as Wharton’s jelly. As a result of its special function, variations in the umbilical cord morphometry is often attributed to the Wharton’s jelly free fatty acids other than the cord vessels [4].
Owing to the important role played by serum cholesterols in the Wharton’s jelly functions as well as energy requirement and its influence on plasma membrane of cells of the developing fetus. It is imperative that endogenous cholesterol synthesised by the fetal tissues alone may not be enough and thus maternal-fetal cholesterol transfer is necessary in order to meet the cholesterol demand of the fetus. This is evident by the positive correlation observed between maternal and umbilical cord cholesterols in term pregnancies [5]. Maternal circulating cholesterol levels are known to relate to changes in umbilical cord vein functions [6]. The umbilical cord vein returns oxygenated blood to fetal heart while cord arteries return deoxygenated blood to the placenta. This practically implies that, all essential nutrient substrates from the mother across the placenta are conveyed to the fetus by the umbilical cord vein [7]. Also, volume of blood flow is a function of blood velocity and cross sectional area of vessels [8]. Hence, structural abnormalities of the umbilical cord vessels may associate with vascular resistance and in turn leads to hypoperfusion, poor transfer of nutrient-rich blood to the fetus and deficiencies in eliminating metabolic waste products.
Systemic arterial blood pressure, commonly called blood pressure (BP) is measured and recorded as systolic over diastolic pressures. The systolic pressure as the numerator is larger and corresponds to arterial pressure due to ejection of blood during ventricular contraction (systole), while diastolic pressure is the denominator which corresponds to arterial pressure due to ventricular relaxation (diastole). Studies have found that blood pressure development varies among uncomplicated pregnancies and pregnancies complicated by gestation hypertensive disorders. Although weakly, first and second trimester systolic and diastolic blood pressures directly relate to the development of preeclampsia [9, 10]. Changes in diastolic blood pressure levels are thought to influence preeclampsia development rather than altered systolic blood pressure levels, however, both diastolic and systolic blood pressure levels may indicate cardiovascular adaptation variations which probably influences fetal growth [11]. Following the potential adverse effects maternal lipid levels could have on perinatal outcomes, it is therefore important to develop an accurate, easy to use and cost-effective scientific approach to screen pregnancies at risk of adverse outcomes. The objective of this study was to determine maternal first antenatal care visit biometric indices as potential predictors of umbilical cord morphometric parameters.
Materials and methods
Study design and area
Analytical descriptive cross-sectional study was conducted between April 2016 and October 2019 on umbilical cord, neonates and maternal first antenatal care visit biometric indices. A simple random sampling was used to select a total of 240 pregnant women who attended antenatal care at the Victory Maternity Home and Clinic in Kumasi for the first time and consented to participate were enrolled into the study.
Inclusion and exclusion criteria
Included in the study were mothers who consented to the collection of their blood samples, have a singleton pregnancy with no pregnancy or delivery complication, and from whom the records about her and the neonate were complete.
Exclusion criteria included mothers who did not consent to the blood sample collection, multiple pregnancies, pregnancy or delivery complication, incomplete records about mother and the neonate.
Study variables
The study variables were categorized into umbilical cord and maternal booking biometric indices. After sample preparations, the under listed parameters were measured.
Umbilical cord length
The umbilical cord was immediately clamped at delivery and in all cases; 2.5 cm umbilical cord stump was left on the neonate. Umbilical cords measurements were made with the umbilical cord still attached to the placenta in its entirety using a standard non –elastic measuring tape from the fetal end to its point of insertion into the placenta. The 2.5 cm stump was added to each measurement made.
Umbilical cord diameter
Umbilical cord diameter (UCD) was measured with the use of a pair of electronic Vennier calipers placed outer - to-outer at three different points, precisely at the fetal end (D1), mid portion (D2) and at the placental surface (D3) so the average of these became the diameter of the cord. Wharton’s jelly content was also included in the measurement.
Umbilical cord weight
The cord weight was measured using an electronic weighing scale after the umbilical cord was excised from the placenta. The umbilical cord was then placed on the scale. The measurement was repeated three times and the average of the three weights was taken as the weight of the umbilical cord.
Umbilical cord volume
This was obtained by the use of water displacement method. The umbilical cord after cutting from the placenta was gently lowered into transparent graduated beaker (500 mL capacity) containing water, the initial water volume V1 was noted, and the volume V2 after placing in the cord was also recorded. The difference between V2 and V1 then gave the volume of water displaced and that became the volume of the umbilical cord according to Archimedes principle.
Umbilical cord area
The area of the umbilical cord in a free loop of the umbilical cord was computed using formula for surface area of a cylinder with the assumption that the umbilical cord takes the shape of a cylinder. That is: A = 2πr2L; Where
Maternal booking biometric indices
Maternal booking biometric indices included; total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), systolic and diastolic blood pressures which were obtained on their first ANC visit.
Statistical analysis
In this present study, mean value±SD was used for the descriptive characteristics of the study variables. Multivariate analysis of variance (MANOVA) was employed to model association between maternal booking biometric and umbilical cord indices due to its robust nature in taking care of the confounding factors.
Five umbilical cord indices were also modelled jointly with six predictors of maternal biometric indices using multivariate test. The final refitted model was assessed using Type II MANOVA, Pillai’s test statistics and DDA. The models are presented with coefficients, standard error (SE), t-value and model p-value < 0.05 for each predictor. In this study all statistical analyses were performed with IBM SPSS Version 22.0 (SPSS Inc., Chicago, IL).
Results
The results of umbilical cord morphometry are presented with mean, standard deviation and 95%confidence interval (Table 1). The mean umbilical cord length was 38.10±7.86 cm with 95%CI of 37.11–39.10. Mean value of umbilical cord was 1.04±0.17 cm (95%CI of 1.01–1.06). Umbilical cord area and volume had mean values of 66.10±24.49 cm2 (95%CI = 62.99–69.22) and 34.02±11.16 cm3 (95%CI = 32.60–35.44) respectively. The mean umbilical cord weight was recorded as 65.01±21.35 g with 95%CI of 62.30–67.73.
Descriptive Statistics of Umbilical Cord Measurements
Descriptive Statistics of Umbilical Cord Measurements
UCL = Umbilical cord length, UCD = Umbilical cord diameter, UCA = Umbilical cord area, UCV = umbilical cord volume, UCW = Umbilical cord weight, SD = Standard deviation, CI =Confidence interval, cm = centimetres, cm2 = centimetre square, cm3 = centimetre cube, g = grams.
The descriptive statistics of maternal booking biometric measurements are displayed in (Table 2). Mean of systolic blood pressure was 119.29±28.31 mmHg and had 95%CI of 115.70–122.90. The corresponding mean diastolic blood pressure was 73.84±13.65 mmHg (95%CI = 72.11–75.58). The mean total cholesterol was 4.03±1.10 mmol/L (95%CI = 3.89–4.17) while mean value for triglyceride was 1.48±0.77 mmol /L (95%CI = 1.38–1.58). The respective means and 95%CI for high-density lipoprotein (HDL–C) and low-density lipoprotein (LDL-C) were 1.11±0.47 mmol/L (1.05–1.17) and 2.24±0.84 mmol/L (2.14–2.35) respectively.
Descriptive Statistics of Maternal Booking Visit Biometric Measurements
SP = Systolic blood pressure, DP = Diastolic blood pressure, TC = total cholesterol, TG = Triglyceride, HDL = High-density lipoprotein, LDL = Low-density lipoprotein, SD = Standard deviation, CI = Confidence interval, mmol/L=millimole per litre, mmHg = millimetre mercury.
In determining models for maternal booking biometric and umbilical cord measurements, a stepwise multivariate linear regression was performed. The individual umbilical cord response variables (length, weight, diameter, area and volume) were analyzed against the six maternal booking biometric parameters (explanatory variables) using multivariate linear regression. Generally, the regression model can be expressed as:
Where;
xi ( i = 1, . . . . . . k) is the estimated explanatory variable.
Five regression models were fitted with the umbilical cord response variables (umbilical cord length, diameter, area, volume and weight) against the six maternal booking biometric indices. The results showed that maternal diastolic blood pressure, total cholesterol, triglyceride, HDL-C and LDL-C had similar significant linear effects on predicting the outcome of umbilical cord length, diameter and area, p value < 0.05. In general, the fitted models for umbilical cord length, weight, diameter, area, and volume could respectively be represented as:
Ylen = 29.479 – 0.007MSBP + 0.095MDBP + 2.390MTC + 0.124MTG + 0.242MHDL –3.476MLDL
YWET = 58.727 – 0.031MSBP + 0.227MDBP – 8.218MTC + 1.705MTG + 9.370MHDL + 5.924MLDL
YDIA = 1.012 + 0.001MDBP – 0.135MTC + 0.058MTG + 0.162MHDL + 0.134MLDL
YAREA = 49.056 – 0.071MSBP + 0.241MDBP – 18.032MTC + 9.993MTG + 25.340MHDL + 16.571MLDL
YVOL = 28.175 + 0.005MSBP + 0.077MDBP + 1.441MTC –1.119MTG + 0.899MHDL – 2.419MLDL
Where; Ylen is the predicted umbilical cord length; MSBP is maternal systolic blood pressure; MDBP is maternal diastolic blood pressure; MTC is maternal total cholesterol, MTG is maternal triglyceride; MHDL is maternal high-density lipoprotein; MLDL is maternal low-density lipoprotein; YDIA is predicted umbilical cord diameter; YAREA is predicted cord area; YVOL is predicted cord volume.
The multivariate linear regression models can be used to calculate a score for each of the respective umbilical cord response variable. However, by considering the level of statistical significance in (Table 3), the MMR models for umbilical cord length, diameter and area can be expressed respectively as:
Individual Regression Models between Maternal Biometrics and Umbilical Cord Indices
Individual Regression Models between Maternal Biometrics and Umbilical Cord Indices
Msystolic = Maternal systolic blood pressure, Mdiastolic = Maternal diastolic blood pressure, Mtcholesterol = Maternal total cholesterol, Mtriglyceride = Maternal triglyceride, MHDL = Maternal high-density lipoprotein, MLDL = Maternal low-density lipoprotein, * = p < 0.05, UC = Umbilical cord, EST = Estimated value, SE = Standard error.
In order to agree with the MMR analysis, a Type II MANOVA test: Pillai’s test statistics was conducted to determine which of the six maternal explanatory variables have joint effect on the umbilical cord response variables. The results of the MANOVA test: Pillai’s test statistics is shown in (Table 4). It was observed that maternal total cholesterol, HDL and LDL have joint significant effect on the umbilical indices.
Type II MANOVA Tests: Pillai test statistic of Maternal biometric with Umbilical cord indices
Msystolic = Maternal systolic blood pressure, Mdiastolic = Maternal diastolic blood pressure, Mtcholesterol =Maternal total cholesterol, Mtriglyceride = Maternal triglyceride, MHDL = Maternal high-density lipoprotein, MLDL = Maternal low-density lipoprotein, Df = Degree of freedom, test stat = test statistic, approx. f = approximation factor, num Df = numerator degree of freedom, den Df = denominator degree of freedom, Pr(>F) = Probability of an F-ratio greater than that obtained by this analysis.
A post hoc MANOVA procedure; descriptive discriminant analysis (DDA) was further conducted to establish a set of perfectly uncorrelated linear equations that together model the differences among the response variable. Therefore, the models were refitted with only the significant predictors from the joint effect test (Table 5).
Refitted Models for Maternal Booking Visit TC, HDL and LDL with Umbilical Cord Length and Diameter
EST = Estimated value, SE = Standard Error, UC = Umbilical cord, TC = Total cholesterol, HDL = High-density lipoprotein, LDL = Low-density lipoprotein, * = p < 0.05.
The mathematical functions that could predict the umbilical cord length and area using maternal booking lipids are respectively given as:
Ylength = 35.814 + 2.326MTC – 3.314MLDL . (R2 = 0.68).
Where; YLength is the predicted umbilical cord length. YArea = 1.022 + 0.059MHDL. (R2 = 0.42).
Where YArea is the predicted umbilical cord area.
The mean values for umbilical cord measurements reported by the present study were; cord length, 38.10±7.86 cm; diameter, 1.04±0.17 cm; area, 66.10±24.49 cm2 and volume was 34.02±11.16 cm3. The mean cord weight was 65.01±21.35 g. These observed measurements are closer to earlier studies conducted in Kumasi [12, 13]. The cord length and diameter in the present study are lower than that recorded in other studies, but these mean values are considered to fall within the normal ranges as reported [14, 15]. In this current study, mean values of maternal booking biometric parameters included 119.29±28.31 mmHg systolic blood pressure 73.84±13.65 mmHg diastolic blood pressure, 4.03±1.10 mmol/L total cholesterol, 1.48±0.77 mmol/L triglyceride, 1.11±0.47 mmol/L HDL-C and 2.24±0.84 mmol/L LDL-C. This finding of the present study clearly indicates that, the study participants were healthy as mean values were within the normal ranges of the respective parameters. Both American Heart Association and American College of Cardiology define normal blood pressure as systolic pressure < 120 mmHg and diastolic pressure < 80 [16, 17]. the Japanese Society for Hypertension also defines normal blood pressure as systolic pressure < 125 mmHg and diastolic pressure < 80 mmHg [18]. The European Society of Cardiology also describes normal blood pressure as 120 –129 mmHg systolic pressure and 80–84 mmHg diastolic pressure [19]. A study on worldwide trends in blood pressures found the global age –standardized mean systolic and diastolic pressures of 122.3 mmHg and 76.7 mmHg respectively [20].
According to these reports, it presupposes that the maternal booking systolic and diastolic blood pressures recorded in the present study align themselves to the definitions of blood pressure by American Heart Association and American College of Cardiology than with the definitions of European Society of Cardiology, Japanese Society for Hypertension and Non-Communicable Disease Risk Factor Collaboration (NCD –RisC). In comparing the maternal booking serum concentrations of total cholesterol, triglyceride, HDL –C and LDL –C found in this current study with first trimester concentrations of maternal lipids from other studies, it was realized that the mean values of this study were lower than first trimester mean values recorded in those studies [21, 22]. This is in line with the observations that maternal serum concentrations increase significantly with advancement in gestation. The rise in lipid concentration levels as pregnancy progresses is attributed to the increased fetal energy demand on maternal metabolism. There is therefore a switch from carbohydrate metabolism in providing energy to lipid metabolism which serves as alternative energy pathway for the developing fetus. Also there is high demand for cholesterol in the synthesis of plasma membranes of the cells as organogenesis begins [23].
Maternal first antenatal care visit biometric and umbilical cord indices modeling
Five models were fitted with umbilical cord response variables (Length, weight, diameter, volume and area) against six maternal explanatory variables (systolic and diastolic blood pressures –SBP and DBP, total cholesterol –TC, triglyceride –TG, high-density –HDL-C and low-density –LDL-C lipoproteins). Explanatory variables which showed statistically significant at p < 0.05 in the regression models were refitted into a final model.
The initial multivariate linear regression models indicated that there were significant joint effects of booking diastolic blood pressure with umbilical cord length, total cholesterol with cord diameter, triglyceride with cord area, HDL-C with cord diameter and area and LDL-C with cord area. These maternal booking explanatory variables were refitted into a final model using Type II MANOVA Test: Pillai’s Test statistic produced results which showed that booking systolic and diastolic blood pressures and triglyceride could not independently influence the outcome of umbilical cord indices. However, maternal booking total cholesterol, HDL-C and LDL-C significantly could influence umbilical cord indices. In the final post hoc analysis, it was observed that a unit increase in the maternal booking explanatory variables implied the following: total cholesterol could increase umbilical cord length by 2.33 units, HDL-C also resulted in a 0.06 unit increase in cord diameter while LDL-C decreases cord length by 3.31 units.
The finding from present study indicating that a unit increase in maternal booking total cholesterol resulted in 2.33 units increase in umbilical cord length presupposes that increase in umbilical cord length is not only influenced by the tension theory [24], and genetic principles [25], but also maternal pregnancy total cholesterol levels. Available evidence suggests that maternal cholesterol becomes the fetus’s main source of cholesterol supply in early parts of pregnancy for most structural and functional developments [26, 27]. Cholesterol is essential requirement for cell proliferation, structural development, cell differentiation, cellular communication and oxysterol necessary for metabolic activity [5]. Wharton’s jelly possesses large quantities of cholesterol esters. Cholesterol has been shown to exhibit concentration –effect on membranes and as such regulates membrane permeability through conformational sequencing of the lipid chains [28]. These could contribute to structural changes of cord length. This is also supported by the significant correlations found between maternal and umbilical cord blood lipids and neonatal outcome [29].
Significant influence of HDL-C on umbilical cord diameters is also reported by the finding of this current study, where a unit increase in maternal booking HDL-C results in 0.06 units increase in cord diameter. Wharton’s jelly characteristics determines the umbilical cord area and hence its diameter. It is known fact that mechanical and morphological nature of the umbilical cord is influenced by the Wharton’s jelly content [30]. Physiological role played by maternal booking HDL-C in influencing the cord diameter is unknown, however, it has been reported that HDL-C is involved in reverse transport of cholesterol, where it picks up excess cholesterol from surrounding cells and tissues and exports them to the liver for breakdown into bile substance [29], For this reason, HDL-C is able to reduce cholesterol levels in the Wharton’s jelly.
Another finding of present study was the observation that a unit increase in maternal booking LDL-C corresponded with 3.31 units decrease in umbilical cord length. In as much as the exact explanation to this observation could not be offered, it is known that factors such as tissues sensitivity to changes in metabolism, responsiveness to mechanical irritation and sensitivity to certain hormones could exert influence on organ development and consequently, causing anatomical, physiological or metabolic disturbances [31]. Again, small, dense LDL particles are subfractions of LDL -C known to be more likely to generate oxidized LDL species. When tissues are exposed to oxidized LDL, it initiates a chain of endothelial responses such as inhibiting release of vasorelaxation factor (nitric oxide) which has inflammatory and antithrombotic characteristics, controls endothelial permeability and angiogenesis modulation [32]. Another explanation offered for the adverse effect of increased maternal booking LDL-C levels on fetal organ systems development was multifactorial mediations of the various subclasses of LDL-C following modified epigenetic transmission mechanisms which may be passed on to the gametes or the intrauterine environment through nutrient supply [33]. The interplay of these could promote an adverse metabolic milieu for the determination of umbilical cord indices outcome.
Conclusion
The mean values of umbilical cord indices observed in this current study were similar to the findings of previous studies conducted in the Kumasi Metropolis on normal uncomplicated pregnancies.
It was found that maternal booking diastolic blood pressure could predict umbilical cord length, while TC, HDL-C. LDL-C and TG and HDL-C levels could significantly predict the outcome of umbilical cord diameter and area respectively. However, maternal booking TC, HDL-C and LDL-C could influence the outcome of umbilical cord indices. Individually, a unit increase in levels of maternal booking TC could results in 2.33 units increase in cord length, while HDL-C could lead to 0.06 unit increase in cord diameter and LDL-C also results in 3.31 units decrease in cord length.
Footnotes
Acknowledgments
This study was supported by the staff of Victory Maternity Home and Clinic in the sample collection process and the technical staff of the Anatomy department. Mr. Christopher Nkrumah of Wenchi Methodist Hospital Laboratory also needs a special mention in this paper for his guidance and direction. Dr. Nana Frimpong Kena of Mathematics Department, KNUST was supportive in the development of the models.
Ethical approval
Prior to the study, ethical approval was obtained from the Committee on Ethics and Human Research for Publication, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology. Kumasi. Ghana. Informed Consent was obtained from the study participants.
Financial and Non-financial competing interest
The authors declare that the research project was self-sponsored, hence there is no financial or non-financial competing interests with anybody or organization.
Data availability statement
The quantitative data used to support the findings of this study may be released upon reasonable application to the Head of Anatomy Department, School of Medicine and Dentistry, Kwame Nkrumah University of Science and Technology, who can be contacted at Telephone: +233 208 126 817 and email: E-mail:
