Document Type : Original Article
Authors
1 obstetrics and gynecology department Faculty of medicine. Alazhar University Cairo ,Egypt
2 obstetrics and gynecology department Faculty of medicine .Alazhar university, cario,EGYPT
Abstract
Keywords
INTRODUCTION
For providing adequate obstetric and neonatal care, precise estimation of gestational age (GA) is essential; including management of diseases through pregnancy with medications which may be considered unsafe during the first trimester, diagnosis of growth restriction or intrauterine growth retardation and post-term pregnancy (≥42 weeks of gestation), Provision of preterm labor antenatal corticosteroids and decisions about whether to administer or withhold intensive care to severely premature babies, which depends mainly on accurate gestational age estimation .1
Growth-restricted fetuses need to be recognized by obstetricians because this fetal condition is correlated with substantial perinatal mortality and morbidity. In fetal, neonatal, and adult life, IUGR can have substantial consequences. 2 IUGR raises the likelihood of intrapartum asphyxia, preterm birth and complications correlated with preterm birth include
but are not limited to, intraventricular hemorrhage, necrotizing enterocolitis and respiratory distress syndrome. Increased occurrence of low Apgar scores, umbilical cord pH lower than 7.0, requirement for intubation, seizures, sepsis and neonatal mortality was also observed in these babies.3 Increased perinatal mortality and morbidity due to a higher likelihood of intrauterine fetal demise (IUFD) and an increased rate of iatrogenic premature birth was correlated with IUGR.4
To evaluate fetal growth, independent parameters for pregnancy age are also required. The maximum transverse diameter of the fetal cerebellum is the transcerebellar diameter (TCD). In the posterior cranial fossa, which resists external pressure and development deviations, the fetal cerebellar hemispheres are found.5 Owing to the brain sparing phenomenon that contributes to sustained blood flow to the brain at the expense of systemic supply, it is relatively resistant to hypoxia.6 It can also be utilized as a tool to help evaluate gestational age in third trimester.7,8 In comparison, the first impacted factor in the process of impaired fetal development is fetal abdominal circumference (AC). Therefore a TCD/AC ratio that becomes independent of pregnancy age is very helpful in forecasting IUGR.
PATIENTS AND METHODS
This study was done at Al Azhar University Hospitals Obstetrics & Gynecology Department from August 1st, 2018 to February 1st, 2020. Patients were selected from outpatient clinic. It is a Prospective observational study. Included 500 pregnant ladies with periods of pregnancy among 18 and 34 weeks. After receiving approval from the Ethical Committee of the Faculty of Medicine, Department of Obstetrics and Gynecology, Al Azhar University . All women solicited for enrollment and given informed written consent.
All patients selected for our study underwent the following conditions: complete history taking include age, history of any medical disorders, and history of any previous operations. Clinical examination including height, weight, gait, vital signs, chest, heart examination and limb examination. Verification of gestational age by the last menstrual cycle prior to 20 weeks of pregnancy and/or ultrasound verification of gestational age by ways of 1st trimester crown rump length measurement. The Voluson E6 system is the ultrasound unit used in this research (Voluson Expert, General Electric Medical Systems, Milwaukee, WI). Either 3 or 5 MHz abdominal transducers have been attached to the system. A trained obstetric sonologist, blinded to gestational age, and a patient id number, inspected every fetus only once. Biometric fetal parameters were measured, such as head circumference, biparietal diameter, transverse cerebellar diameter, abdominal circumference and length of the femur. The cerebellum has been situated in the posterior fossa and visualized at the BPD level by minor posterior and inferior transducer rotations. As specified by Goldstein et al., electronic calipers were used to calculate the TCD in an outer to outer fashion.9 Abdominal circumference (AC) was measured by the cross-section (as circular as possible) of the fetal abdomen; the umbilical vein was visualized at the portal sinus level; the stomach bubble was visualized; the kidneys were not noticeable. The AC was calculated directly by ellipse calipers on the outside surface of the skin line.10 The TCD/AC ratio was measured by dividing the TCD by AC and then multiplying it by 100.11 The research was carried out in the usual way, typically brief, usually lasting around or less than 15 mins, with close attention provided to obtaining a setting suited to create the best image possible. In order to mitigate the error obtained from the caliper method, image magnification has been attempted.
Criteria for inclusion: Pregnant ladies with singleton uncomplicated pregnancy before 20 weeks of pregnancy at gestational age.
Criteria for exclusion: Women with multiple gestation, history of metabolic disease, any maternal medical conditions complicating pregnancy (hypertension, diabetes mellitus, renal disease, cardiac conditions, etc.), fetal congenital anomalies were excluded.
Outcome: pulation specific transcerebellar diameter/abdominal circumference ratio (TCD/AC ratio) for the evaluation of natural fetal development in women who attend Al Azhar University hospitals. Investigate other TCD based ratios for evaluation of natural fetal development. Investigate sensitivity, specificity and predictive value of TCD/AC ratio in evaluation of natural fetal development.
Statistical Methods: Using the statistical software SPSS (statistical package for social science version 26.00), all statistical calculations were performed, at 0.05, 0.01 and 0.001 likelihood levels 18. Non-parametric quantitative data distribution was conducted using the Mann Whitney variance analysis to compare two groups, and three groups were compared using the Kruskal Wallis test. The best cut-off point with its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under curve (AUC) has been evaluated by the receiver operating characteristic curve (ROC) using Medcalc (version 15.80). The confidence interval became set at 95% and the accepted error margin became set at 5%. The p-value at the level of >0.05 was deemed to be non-significant (NS), significant at the <0.05, 0.01 level, and extremely significant at the 12
RESULTS
Variable |
||
Age (years) |
Range |
20.0-35.0 |
Mean ±SD |
29.32±4.90 |
|
Height (m) |
Range |
1.5-1.8 |
Mean ±SD |
1.68±0.11 |
|
Weight (kg) |
Range |
46.5-96.0 |
Mean ±SD |
66.66±15.68 |
|
BMI (kg/m2) |
Range |
16.5-32.9 |
Mean ±SD |
23.74±5.57 |
|
Gestational age by LMP (days) |
Range |
126-238 |
Mean ±SD |
195.89±45.90 |
|
Gestational age by LMP (weeks) |
Range |
18-34 |
Mean ±SD |
24.49±5.60 |
|
Gestational age by US (days) |
Range |
127-245 |
Mean ±SD |
192.24±37.01 |
|
Gestational age by US (weeks) |
Range |
18.1-34.9 |
Mean ±SD |
27.49±5.86 |
Table 1: Descriptive statistics for the whole study cohort (gestational age 18-34 weeks): Numerical variables (N=500).
Variable |
||
BPD (cm) |
Range |
3.7-8.9 |
|
Mean ±SD |
6.43±2.07 |
HC (cm) |
Range |
13.1-32.4 |
Mean ±SD |
28.89±8.40 |
|
AC (cm) |
Range |
11-33.6 |
Mean ±SD |
22.94±5.01 |
|
FL (cm) |
Range |
2.7-7.1 |
Mean ±SD |
5.33±1.35 |
|
TCD (cm) |
Range |
1.6-4 |
Mean ±SD |
3.07±1.36 |
|
TCD/AC ratio |
Range |
8.54-16.87 |
Mean ±SD |
12.10±2.20 |
|
TCD/BPD ratio |
Range |
22-53.43 |
Mean ±SD |
39.50±9.81 |
|
TCD/HC ratio |
Range |
4.76-15.6 |
Mean ±SD |
9.90±3.07 |
|
TCD/FL ratio |
Range |
34.9-77.9 |
Mean ±SD |
45.79±12.64 |
|
EFW (g) |
Range |
190-2648 |
Mean ±SD |
1175.86±579.87 |
Table 2: Descriptive statistics for the whole study cohort’s biometry (gestational age 18-34 weeks): Numerical variables (N=500).
Variable |
Frequency |
Percent |
|
Parity |
P0 |
182 |
36.40% |
P1 |
168 |
33.60% |
|
P2 |
126 |
25.20% |
|
P3 |
18 |
3.60% |
|
P4 |
6 |
1.20% |
|
Previous CS |
No previous CS |
342 |
68.40% |
Previous CS |
158 |
31.60% |
|
Previous abortion |
Nil |
438 |
87.60% |
Once |
52 |
10.40% |
|
Twice |
10 |
2.00% |
|
IUGR |
No IUGR |
415 |
83.00% |
IUGR |
85 |
17.00% |
Table 3: Descriptive statistics for the whole study cohort (gestational age 18-34 weeks): Categorical variables.
Variable |
No IUGR N= 415 |
IUGR N= 85 |
p-value |
|
Median (IQR) |
Median (IQR) |
|||
Gestational age 18-34 weeks |
TCD (cm) |
3.97 (2.40-3.90) |
3.01 (2.30-3.90) |
|
TCD/AC ratio |
11.00 (9.87-13) |
16.00 (12.-17.0) |
||
TCD/BPD ratio |
45.00 (29.0-47.00) |
44.1 (27.0-50.00) |
0. 340 ns |
|
TCD/HC ratio |
10 (7 -13) |
9 (8-10.0) |
0.081 ns |
|
TCD/FL ratio |
40.00 (36.1 -60) |
36 (34.9 -38) |
Table 4: Comparison of the TCD and related measures in patients with or without IUGR in whole cohort study group.
Fig 1: Shows a highly statistically significant variation among patients with IUGR and patients without IUGR according to TCD , TCD/AC ratio and TCD/FL ratio in whole cohort study group.
Cut off point |
AUC |
Sensitivity |
Specificity |
+PV |
95% Cl |
-PV |
95% Cl |
Z test |
p value |
TCD/AC ratio >13 |
0.937 |
99.03 |
83.45 |
58.0 |
50.3 - 65.3 |
99.7 |
98.5 - 100.0 |
40.65 |
<0.0001 |
Table 5: Receiver-operating characteristic (ROC) curve analysis at 18-34 weeks for differentiation among patients with or without IUGR.
Fig 2: Diagnosis of IUGR at 18-34 week using TCD/AC Ratio.
DISCUSSION
A common and complex obstetric issue has been intrauterine growth restriction (IUGR). It is estimated that IUGR affects nearly 10-15% of women who are pregnant.13 The perinatal rate for unscreened/ undetected SGA is 21.3 per 1,000 live births compared with 8.4 for screened/detected SGA (RCOG Guideline No. 31). Thus it is necessary to identify these fetuses, begin early antenatal surveillance and implement prompt obstetric measures to decrease perinatal mortality. Compared with SGA children, IUGR babies are reported to have an elevated risk of adverse short- and long-term effects.3
IUGR is often induced by asphyxia or decreased flow of utero-placental blood. The flow of blood primarily transfers to the central parts of the heart, brain, and adrenal glands (Loughna, 2006). There has been a research that cerebellar blood flow stayed constant in acute asphyxia as a result of cardiac output redistribution.14 Cerebellar growth in humans is less influenced by IUGR, so measuring of TCD is mostly effective in predicting gestational age.15 Hepatic glycogen and subcutaneous fat stocks have reduced in IUGR fetuses, resulting in reduced AC. Thus the AC has been sensitive for predicting fetal IUGR.16 The TCD/AC ratio has been the biometric parameter that is the least impacted and might be a sensitive tool at any gestational age to detect asymmetric IUGR.
This study that included 500 Egyptian women with uncomplicated normal pregnancy who attended the antenatal clinic for routine scan with Mean (SD) of age was 29.32(4.9) years, as regards Mean (SD) of BMI were 23.74(5.57) and as regards the parity 36.40% were PG, 34.60% were P1, 25.20% were P2, 3.60% were P3 and 1.20% were P4., Mean (SD) gestational age by Last menstrual period (LMP) was 24.49, we have found that the average TCD/AC ratio for the various gestation periods was:
18-22 weeks |
10.98 |
23-26 weeks |
12.21 |
27-30 weeks: |
12.58 |
31-34 weeks: |
12.67 |
While Dhumale et al. 17. who conducted a prospective observational research at the teaching hospital of KLE University, Belgaum on 434 obstetric patients 18-34 weeks of singleton pregnancy and confirmed gestational age similar to this study found that Mean for TCD/AC ratio for the various gestation periods was:
18-22 weeks |
13.4 |
23-26 weeks |
13.5 |
27-30 weeks: |
13.6 |
31-34 weeks: |
14.0 |
It was found that difference in TCD/AC ratio between patients with IUGR vs. patients with no IUGR are statistically significant in all gestational age groups with a p-value of <0.001, also agreed with Dhumale et al.
Our study showed that TCD/AC seems to have an excellent predictive value in 18-34 weeks gestational age groups with Best cutoff value on TCD/AC ratio of >13 this cutoff value with 99.03% sensitivity and 83.45 % specificity, 58.0 with a positive predictive value and 99.7 with a negative predictive value. That agreed by Dhumale et al. in which they stated that the TCD/AC ratio in the gestational age group 18-34 weeks is an age independent constant parameter and a comparatively good indicator of IUGR.
While in earlier studies Chawanpaiboon et al.18 conducted on a total of 634 women who are pregnant among 13 and 40 weeks of pregnancy and attending the Siriraj hospital antenatal clinic, discovering that the TCD/AC ratio is a stable, gestational age independent parameter between 20-30 weeks of pregnancy which could be helpful in early diagnosis of fetal intrauterine growth retardation (IUGR).
In our study difference in TCD between patients with IUGR vs. patients with no IUGR was statistically significant in all gestational age groups.
TCD is effective and accurate even at extremes of fetal growth in predicting GA.19 It was found that the transcerebellar diameter among normal and growth-restricted fetuses was the same. This parameter can also be used as one of the significant methods for evaluating pregnancy age in normal and growth restricted fetuses.20 Cerebellar size is decreased in the case of intrauterine growth retardation (IUGR) in relation to the seriousness of the disease and thus the TCD cannot be used to gain accurate info on the gestational age of small fetuses and the TCD/AC ratio cannot provide accurate data on whether or not fetuses are growth retarded fetuses.21 For fetuses with asymmetric but not symmetric growth restriction, TCD is a helpful indicator of pregnancy age.22
CONCLUSION
This study concluded that difference in TCD/FL ratio between IUGR vs. patients with no IUGR is statistically significant in 18 -34 weeks gestational age groups difference in TCD/BPD and TCD/HC ratio between patients with IUGR vs. patients with no IUGR is statistically significant. As shown in the ROC curve comparisons for all gestational age groups TCD/AC ratio has good predictive value for discrimination between patients with IUGR and patients with no IUGR in gestational age group 18-34weeks compared to other TCD based ratios and all are statistically.