Early Simplified Method Of Screening Of Iugr Biology Essay

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Introduction: Could ultrasonography be performed early in pregnant women as a screening test to predict IUGR? To justify its use, it must have a high enough positive predictive value.

Materials and methods: This study addresses the concept of early prediction of IUGR using echographic measurements in the first trimester. We studied one traditional and one new marker: the crown-rump length (CRL) and the cerebro-corporal coefficient (CCC). We retrospectively reviewed the charts of 450 pregnancies that gave birth to babies with IUGR and 25 charts of normal pregnancies that made the control group. Screening in the first trimester of pregnancy was done in 300 (89.9%) pregnant women between 10 and 14 weeks. We calculated the diagnostic and predictive values of these two parameters in IUGR.

Results: The sensitivity and specificity for reduced CRL were 29 and 100%, respectively, and for the CCC > 0.6, 46 and 100%, respectively. Using IUGR prevalence (10%) and the Bayes equation we calculated the positive predictive value of reduced CRL and > 0.6 CCC in general, moderate and severe IUGR and severe IUGR alone. They were 1, 1, 9%, 13, 19 and 29%, respectively.

Conclusion: The positive predictive value of the crown-rump length and the cerebro-corporal coefficient for IUGR in the general population increases with the severity of the disease. Using these two parameters, however, would be more useful in high-risk pregnancies.

Keywords IUGR Screening; Crown-rump length; Cerebro-corporal coefficient

Introduction

The ability to visualize the fetus with ultrasonography has dramatically changed the practice of obstetrics. Physicians caring for pregnant women can now determine gestational age and diagnose abnormalities during pregnancy with much greater accuracy than before. The use of sonography in problem pregnancies is widely encouraged.

These conditions include errors in gestational age, twin pregnancies, intrauterine growth restriction (IUGR), congenital anomalies, placenta previa, macrosomia, and fetal malpresentation. Women whose fetuses are labeled as IUGR have higher risks and costs of antepartum testing and higher rates of labor induction and cesarean sections. Most clinical studies demonstrate that when using physical examination alone the diagnosis of IUGR is missed or incorrectly made almost in half of cases [1].

The first screening tool in the general obstetrical practice for IUGR is the symphyseal- fundal height (SFH) measurement. The inherent limitations of the low sensitivity (27%) and the wide positive predictive value (29-79%) of SFH make it unreliable in detecting IUGR, especially in low-risk mothers [2, 3]. This is particularly important after 36 weeks, as most fetal deaths involving IUGR occur after 36 weeks of gestation and before labor begins. However, this is the first net that many cases of IUGR slip through. The incorporation of an efficient early prediction of IUGR, resulting in appropriate action being taken when required presents a major challenge.

Unless we do better in the initial clinical screening, we cannot expect to improve our outcome. Among the attempts to improve accuracy, one may use a single bio- metric parameter to predict growth abnormalities early in pregnancy. The crown-rump length has been shown in a recent study to influence final birth weight but with a predictive power not sufficiently good to be used alone for IUGR screening [4]. This paper compares the predictive value of two embryometric measurements using ultrasound in the first trimester for the early prediction of IUGR.

Materials and methods

After obtaining the approval of the Scientific Council of El-Minya University, we retrospectively studied the charts of 300 pregnancies that gave birth to babies with IUGR between 2006 and 2008 and 25 charts of normal pregnancies that represented the control group. The diagnosis of IUGR was established on the basis of regional normatives of birth weight. Echographic measurements were collected and compared with regard to their diagnostic and predictive value.

In this study, we were interested mainly in the crown-rump length (CRL) and the cerebro-corporal coefficient (CCC) as the most feasible ultrasound markers in the first trimester that can be used to predict IUGR in the general population.

CRL is the length of the embryo in the natural C-shaped state with an un- stretched body. The measurement of CRL is useful in determining the gestational age and the expected date of delivery. Different babies do grow at different rates and thus, it may play a role in predicting IUGR. CCC, a new parameter, is defined as the relation of the length of the head part to the body part of the embryo (Fig. 1).

Figure (1) shows a sonographic view of a fetus of nearly 11 weeks, demonstrating the ratio between the tranditional crown rump length (CRL) and the proposed cerebro-corporeal coefficient (CCC). The proposed new coorelation is quite easy to be assessed in few minutes. It is important to put the scan view in the best sagittal scan, to get the best corrected parameters. The scan view required is the same required to assess the CRL length, so we could assess both in the scan plan.

Figure (1)

Figure (1) The Crown-Rump length (CRL) and the cerebro-corporeal coefficient (CCC)

A is the head length, and B is the Body length

Figure (1) shows a sonographic view of a fetus of nearly 11 weeks, demonstrating the ratio between the tranditional crown rump length (CRL) and the proposed cerebro-corporeal coefficient (CCC). The proposed new coorelation is quite easy to be assessed in few minutes. It is important to put the scan view in the best sagittal scan, to get the best corrected parameters. The scan view required is the same required to assess the CRL length, so we could assess both in the scan plan.

We started measuring this coefficient in our department in an attempt to find a marker-predictor that can be used early in pregnancy to predict IUGR later in the third trimester. Ultrasound investigation of fetuses was performed using ''Logiq-5'' and ''Toshiba-530''. The reproduction of measurement was tested using three measurements by the same ultrasound specialist and other three measurements performed by three independent specialists; the error did not exceed 0.1.

In our study, we have analyzed 300 newborns with various degrees of IUGR. The clinical material was divided into four groups according to the presence and severity of IUGR using the clinico-diagnostic criteria of NP Shabalov and VV Abramchenko (Table 1); [5].

1. The first group (n = 50), the control group, included at-term-born babies from uncomplicated pregnancies with a satisfactory condition at birth, early neonatal period without peculiarities and baby discharged healthy.

2. The second group (n = 90) included at-term-born babies with first degree IUGR, condition at birth satisfactory and mild metabolic disturbances during early neonatal period.

3. The third group (n = 96) included at-term-born babies with second degree IUGR, hypoglycemia, polycythemia, improvement over the early neonatal period.

4. The fourth group (n = 64) included preterm-born babies (30-36 weeks) with second and third degrees IUGR that necessitated reanimation measures in the early neonatal period. In this group, there were 14 (15.6%) at-term-born babies with severe IUGR born in serious condition and 13 (12.5%) cases of perinatal death.

Results

Table (1) The standard criteria for diagnosis of IUGR after labour. The parameters included are: Body mass deficit in relation to the body length, the skin viability index, the amount of subcutaneous fat, the muscle mass index, the head shape and size parameters, and finally the growth progress during the early neonatal period. Those parameters might be a little pit complicated, which opens the way for the current research and similar work for easier ways to detect those IUGR cases as early as possible.

Table (1)

Table (1) Clinica-diagnostic signs for IUGR grading (VV Abramtshenko, NP Shabalov 2004)

Severe

Medium

Mild

Sign

>3 c

>2 c

>1.5 c

Body mass deficit in relation to body length

Pale, wrinkly, dry skin with scales and often cracks

Pale, dry and scaly skin with possible cracks

Absent or decreased elasticity

Skin trophy disturbamces

Totally absent

Absent in the abdomen

Thin everywhere

Subcutaneous fat

Skin folds on the buttocks, face and torso

Markedly decreased, flabby transverse folds on the extremities

Not changed and/or slightly decreased

Tissue turger

Decreased, especially in the buttocks and thighs

Decreased, especially in the buttocks and thighs

Not changed

Muscle mass

Looks enlarged, exceeds thorax circumference by >3cm. Sutures are wide. Anterior fontanel sunken wit soft pliant edges

Looks enlarged, exceeds thorax circumference by >3cm. Sutures are wide. Anterior fontanel sunken wit soft pliant edges

Circumfrence within normal limits, hair not changed

Head

As a rule, complicated with prevailing signs of brain and cardiovascular injury, infection, anaemia, late appearance of suckling reflexes, marked thermolability, often metabolic disturbances, hemorrhagic syndrome

Usually complicated asphyxia or signs of chronic intrauterine hypoxia, thermolability, often polycytosis, hypoglycaemia, hypocalcymia, hyperbilirubinemia, sometimes seizures, respiratory disturbances, edems, muscular hypotonia and hyporeflexia

Either without complications or with manefistations of excessive birth stress, mild metabolic disturbances, sometimes with signs of energetic deficiency

Progress of early neonatal period

The standard criteria for diagnosis of IUGR after labour. The parameters included are: Body mass deficit in relation to the body length, the skin viability index, the amount of subcutaneous fat, the muscle mass index, the head shape and size parameters, and finally the growth progress during the early neonatal period. Those parameters might be a little pit complicated, which opens the way for the current research and similar work for easier ways to detect those IUGR cases as early as possible.

Table (2) The table shows the relationship between the different clinical pictures of IUGR babies and the change of the CRL values. According to this relation, the IUGR cases have been classified into four clinico-pathological groups, indicating the severity and the prognosis of the case.

Table (2)

Table (2) Crown-rump length (CRL) values by clinical groups

CRL Clinical groups Total (n= 300)

-------------------------------------------------------------------------------------------------------------------------------------------

I (n= 50) II (n= 90) III(n= 96) IV(n= 64)

Abs. % Abs % Abs. % Abs. % Abs %

Coeformity to gest. Age 46 92 78 80 48 50 24 37.5 196 62.0

---------------------------------------------------------------------------------------------------------------------------------------------------------

Reduction 0 0 6 13.3 36 37.5 38 59.3 80 30.0

---------------------------------------------------------------------------------------------------------------------------------------------------------

Increase 4 8 6 6.7 12 12.5 2 3.1 4 8.0

The table shows the relationship between the different clinical pictures of IUGR babies and the change of the CRL values. According to this relation, the IUGR cases have been classified into four clinico-pathological groups, indicating the severity and the prognosis of the case.

Screening investigation in the first trimester of pregnancy was done in 300 (89.9%) pregnant women between 10 and 14 weeks. Conformity of the CRL to gestational age was determined using the percentile values of Medvedev 2002 [6].

As we see from Table 2, in the control group, in 46 (92%) pregnant women, the CRL of the embryo corresponded to normal values for gestational age, there were 4 (8%) cases in which increased values of CRL were registered that was probably due to constitutional reasons.

There was no reduced CRL in the control group. In the second group, the CRL corresponded to normal values for gestational age in 132 (80%) pregnant women. In 12 (13.3%) cases, a reduction of the given parameter was noted which we considered an early predictor of primary placental insufficiency and consequently of intrauterine growth retardation.

In 6 (6.7%) cases, an increase in this parameter was registered. In the third group, in 48 (50%) pregnant women, CRL of the embryo corresponded to normal values for gestational age. This is less than in the first and second groups.

In 36 (37.5%) cases, there were decreases in the given parameter which supported the hypothesis above. In 12 (12.5%) cases, there was an increase in this parameter. In the fourth group with a severe degree of IUGR, only 24 (37.5%) embryos had CRL corresponding to normal values for gestational age which was considerably less than in the first, second, and third groups.

In 38 (59.3%) cases, reductions in the given parameter were noted. An increase in this parameter was registered in 2 (3.1%) case only. In our search for a predictor of IUGR in the first trimester, we evaluated a new ultrasonic marker, the CCC, which is the ratio of the length of the embryonic head to the length of the trunk.

We hypothesized that a disproportion in the development of the embryonic parts would help predict the development of IUGR later in pregnancy. The measurement is to be done in a frontal scanning plane of the embryo head and trunk between 10 and 14 weeks gestation.

Earlier use of this parameter in pregnancy is impossible due to the absence of anatomic differentiation of the embryo into head and trunk. Later, this parameter is difficult to measure because of beginning of functioning of the tone center in the neural tube and assuming the natural bending position by the embryo. Norml values of 0.4-0.6 mean that the length of the trunk is approximately equal to the length of the head. Values more than 0.6 and less than 0.4 are considered pathological.

As we see from Table 3, in the control group with 50 (100%) pregnant women, the CCC of the embryo corresponded to normal values. In the second group, in 70 (77.8%) pregnant women, the CCC corresponded to normal values; in 18 (13.3%) cases, an increase in the given parameter was noted which we considered an early predictor of primary placental insufficiency and consequently of intrauterine growth retardation; and in 2 (2.2%) case, a reduction in this parameter was registered. In the third group, in 40 (41.7%) pregnant women, the CCC of the embryo corresponded to normal values for gestational age, which was less than in the first and second groups.

In 4 (4.1%) cases, there were reductions in the given parameter; and in 52 (54.2%) cases, there was an increase in this parameter. In the fourth group with a severe degree of IUGR, only 14 (21.9%) embryos had CCC corresponding to normal values for gestational age which was considerably less than in the first, second and third groups. In 6 (9.3%) cases, there were reductions in the given parameter, which probably was the starting moment in the development of future IUGR. In only 44 (68.8%) cases, an increase was registered that was probably due to a mistake in measurement. Forty-two percent of fetuses in the basic group showed a change in CCC.

It is known that sensitivity and specificity of a test do not depend on the prevalence (pre-test probability) of disease. We calculated the diagnostic and predictive values of these two parameter in IUGR in general. The sensitivity and specificity for the reduced CRL were 29 and 100%, respectively, and the sensitivity and specificity of > 0.6 CCC were 46 and 100%, respectively.

In Table 3, the control group with 50 (100%) pregnant women, the CCC of the embryo corresponded to normal values. In the second group, in 70 (77.8%) pregnant women, the CCC corresponded to normal values; in 18 (13.3%) cases, an increase in the given parameter was noted, and in 2 (2.2%) case, a reduction in this parameter was registered. In the third group, in 40 (41.7%) pregnant women, the CCC of the embryo corresponded to normal values for gestational age. In 4 (4.1%) cases, there were reductions in the given parameter; and in 52 (54.2%) cases, there was an increase in this parameter. In the fourth group with a severe degree of IUGR, only 14 (21.9%) embryos had CCC corresponding to normal values for gestational age which was considerably less than in the first, second and third groups. In 6 (9.3%) cases, there were reductions in the given parameter

Table (3)

Table (2) Cerebro-Corporeal Coefficient (CCC) values by clinical groups

CCC Clinical groups Total (n= 300)

-------------------------------------------------------------------------------------------------------------------------------------------

I (n= 50) II (n= 90) III(n= 96) IV(n= 64)

Abs. % Abs % Abs. % Abs. % Abs %

0.4-0.6 50 100 70 77.8 40 41.7 14 21.9 174 58.0

---------------------------------------------------------------------------------------------------------------------------------------------------------

> 0.6 0 0 18 20 52 54.2 44 68.8 114 38.0

---------------------------------------------------------------------------------------------------------------------------------------------------------

< 0.4 0 0 2 2.2 4 4.1 6 9.3 12 4.0

Table (3) demonstrates the co-relation between the newly proposed Cerebro-Corporeal Coefficient (CCC) and the developing IUGR in 3 proposed (CCC) parameters after dividing the included cases into 4 clinical groups as mentioned in the table.

Discussion

An ultrasound examination in pregnancy, unlike other screening procedures, for example sigmoidoscopy, is pleasant to the pregnant woman and often requested by her. Ultrasound imaging of a healthy fetus may be one of the most enjoyable procedures in medical practice.

Since routine ultrasonography is performed in pregnant women as a screening test to detect unsuspected conditions, it must meet several criteria to justify its use. It should have a high enough sensitivity to avoid missing problems, and an acceptably high specificity to avoid working-up too many false-positive diagnoses [7].

Patients should find it comfortable, accessible, and quickly performed. In addition, early diagnosis in the screening phase must offer the opportunity to render therapeutic benefits compared with later diagnosis by selective ultrasonography. Finally, the benefits of routine ultrasound testing should justify its cost as measured in economic terms as well as in human suffering.

The sensitivity, specificity, and predictive value of ultrasound diagnosis varies with the parameter used and the condition detected. Assessment of gestational age, detection of multiple gestation, and diagnosis of congenital anomalies can be attained reliably with sonography under optimal conditions.

Case reports of misdiagnosis of IUGR, however, illustrate the importance of accuracy in prenatal sonography. Mistakes are more likely with universal ultrasound screening, since accuracy is likely to be less than that reported by experts. In addition, false-positive diagnoses are more frequent in screening programs because of the low prevalence of the disease in the general low-risk population. And as long as the IUGR baby is not equal to small-for-gestational age (SGA) baby, the prospective point of view for diagnosing IUGR is required in clinical medicine [8]

IUGR is a good example with which to illustrate the importance of sensitivity, specificity, and predictive value with routine ultrasound use. In our study, we reviewed the charts of 300 pregnancies complicated by IUGR and the results of screening in early pregnancy. Using standard formulas, we calculated the sensitivity and specificity of the reduced CRL measurement for IUGR which came 29 and 100%, respectively.

It is known that the stricter the diagnosis criteria are, the less sensitive and more specific they are. Thus, we raised the cut point for IUGR and calculated the sensitivity and specificity for medium and severe IUGR and they became 46 and 91%, respectively.

The sensitivity increased to 46%, which was still not sufficiently high to be useful knowing that a sensitive test when negative rules out disease and, on the other hand, the specificity decreased. Thus, there is a trade off between sensitivity and specificity.

Resetting the cut point can improve one of them but at the expense of the other. The sensitivity and specificity of > 0.6 CCC for general IUGR were 46 and 100%, respectively. This changed to 60 and 87% when the cutpoint was raised. This marker showed better sensitivity and same specificity as CRL in the first setting and lower specificity in the second setting.

Sensitivity and specificity by themselves are only useful when either is very high (typically C95%) [9]. Predictive values are more practical to clinicians because the main question for them is: given a positive (or negative) test result, what is the probability of disease? But, they vary with the prevalence of the disease itself. Each pair of predictive values (post-test probabilities) is associated with a single pre-test probability.

Changing the pre-test probability changes the predictive value in a non-linear way. The prevalence of IUGR is 10% by definition, since fetuses with an estimated weight of less than 10 percentile are defined as growth restricted [10]. For medium and severe IUGR it would be 7 percentile and for severe IUGR 5 percentile. The positive predictive value (PPV) can be calculated using the Bayes equation: [11].

The positive predictive value (PPV) is the probability that an individual with a positive screening result has the disease. The sensitivity is the probability that an individual with the disease is screened positive and the specificity is the probability that an individual without the disease is screened negative.

Figure (2) demonstrates the graphics of the statistical analysis between the ratio of the CRL and the proposed CCC as a new way to predict the development of IUGR. The proposed ratio results were encouraging especially in high risk cases, but it is recommended to extend the current proposed research for another research work, recruiting only high risk cases.

Figure (2)

Figure (2), The sensitivity, specificity, and positive predictive values PPV

of CCC and CRL for different values of IUGR

Figure (2) demonstrates the graphics of the statistical analysis between the ratio of the CRL and the proposed CCC as a new way to predict the development of IUGR. The proposed ratio results were encouraging especially in high risk cases, but it is recommended to extend the current proposed research for another research work, recruiting only high risk cases.

The prevalence of the disease can be interpreted as the probability that a randomly chosen member of the population being screened has the disease. Thus, using three severity levels, the positive predictive value of reduced CRL and > 0.6 CCC in general, medium and severe IUGR and severe IUGR alone were 1, 1, 9, 13, 19 and 29%, respectively (Fig. 2). Thus, we notice that PPV increases with the severity of the disease and is better for CCC.

The low positive predictive values of these two echo- graphic markers for IUGR are due to the low sensitivities of these markers and the low prevalence of IUGR in the general population. The positive predictive values will be better if screening takes place in high-risk pregnancies like those with low socioeconomic status, smoking, anemia, etc.

This would be the subject for our future research. We should also remind that IUGR usually develops after 32 weeks and these markers are measured between 10 and 14 weeks of pregnancy [12]. Hence, we could say that the CRL and the CCC are not practical for the early prediction of IUGR in the general population but would be more useful in the high-risk population.

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