Epistemic concern

SECOND TRIMESTER THIRD TRIMESTER

50

Table 1: Changes in fetal kidney length with gestational age as observed in this study.

GESTATIONAL AGE (LMP; weeks)

FETAL KIDNEY LENGTH (Mean; mm ± SD)

N

20 20.7056 ± 0.72139 36 21 21.3967 ± 0.34562 15 22 22.1667 ± 0.59107 30 23 23.5217 ± 0.49677 23 24 24.6844 ± 0.61323 90 25 25.9647 ± 0.40161 49 26 26.1969 ± 0.35034 17 27 27.2167 ± 0.57627 21 28 28.6357 ± 0.68922 133 29 29.4431 ± 0.48109 36 30 31.0422 ± 0.77676 64 31 31.3750 ± 0.38358 18 32 32.7112 ± 0.86808 49 33 33.6267 ± 0.48330 30 34 34.3561 ± 0.88347 180 35 35.5589 ± 0.70331 56 36 36.9444 ± 1.08821 125 37 38.0585 ± 0.90966 41 38 39.7643 ± 1.60916 35 39 40.8342 ± 1.17143 19 40 41.4167 ± 0.68459 6

TOTAL 1073

51

Table 2: Changes in fetal biometric indices (BPD, HC, AC and FL) with gestational age as observed in this study.

GESTATIONAL AGE (LMP; weeks)

BPD (mm) Mean ± SD

HC (mm) Mean ± SD

AC (mm) Mean ± SD

FL (mm) Mean ± SD

N

20 48.703 ± 4.1987 194.300 ± 22.1693 167.489 ± 24.1872 35.031 ± 3.8381 36 21 50.287 ± 2.9609 197.940 ± 14.4648 169.393 ± 18.5347 35.193 ± 2.4610 15 22 53.820 ± 4.0685 199.707 ± 10.5110 172.593 ± 10.1290 38.947 ± 3.7077 30 23 56.287 ± 3.1071 212.365 ±14.0576 183.517 ± 15.1092 40.548 ± 2.9139 23 24 60.750 ± 4.2847 229.557 ± 13.8095 204.723 ± 15.1901 44.723 ± 4.0633 90 25 63.592 ± 4.0870 236.749 ± 17.8123 213.678 ± 16.9081 46.833 ± 3.4512 49 26 65.724 ± 2.5198 243.329 ± 14.9191 220.765 ± 13.8420 49252 ± 3.7759 17 27 67.076 ± 4.2965 248.957 ± 19.8870 226.505 ± 24.0405 50.200 ± 4.9790 21 28 70.585 ± 4.4175 258.242 ± 11.8633 242.458 ± 18.0488 53.591 ± 3.6369 133 29 73.911 ± 2.7153 282.581 ± 22.4116 252.161 ± 11.8619 56.653 ± 1.6614 36 30 75.959 ± 3.6065 279.433 ± 12.5489 263.550 ± 11.4844 58.345 ± 2.7808 64 31 77.444 ± 3.1853 295.606 ± 10.7403 265.128 ± 10.8108 59.289 ± 1.9122 18 32 79.780 ± 2.6524 300.483 ± 8.5153 268.859 ± 12.9871 61.847 ± 2.7738 49 33 81.823 ± 2.7423 306.873 ± 15.0818 279.417 ± 19.9158 64.987 ± 3.4975 30 34 84.226 ± 4.1137 316.736 ± 11.8155 291.041 ± 19.3887 65.383 ± 4.1021 180 35 87.364 ± 3.0783 326.736 ± 10.7152 308.318 ± 13.0951 68.398 ±2.9145 56 36 91.200 ± 3.8361 328.407 ± 9.5156 323.948 ± 18.0651 72.238 ± 3.1708 125 37 91.393 ± 3.4227 331.039 ± 17.6986 324.024 ± 13.2665 72.520 ± 2.4374 41 38 92.411 ± 2.4480 339.123 ± 11.5227 332.279 ± 15.0168 74.242 ± 3.2635 35 39 93.626 ± 2.9193 342.816 ± 7.5429 332.940 ± 15.4863 74.369 ± 2.1046 19 40 97.767 ± 1.3692 350.433 ± 4.3122 345.900 ± 13.3005 79.867 ± 1.8554 6

TOTAL 1073

52

The fetal biometric indices measured (BPD, HC, AC and FL) all showed a strong positive linear relationship with the gestational age (in weeks). These are depicted in figures 19-21. This relationship with the gestational age was also observed with the fetal kidney length as illustrated in figure 22. The strongest correlation was observed between LMP and the FL; R=0.97; followed by FKL; R=0.96, while the least correlation was exhibited between LMP and AC; R=0.94 (p<0.001) (see Table 3). ANOVA linear regression analysis was used to assess the accuracy of the individual biometric indices (including fetal kidney length) in predicting the gestational age between 20-40 weeks of gestation (see Table 4). The most accurate was the FL with a standard error (SE) of 3.58 days, followed by the FKL (SE: 3.62 days) and BPD (SE: 4.90 days). The least accurate at predicting gestational age were the HC (SE: 15.99 days) and AC (SE: 17.57 days) respectively.

The derived models for predicting gestational age (GA) using a combination of various biometric indices (including fetal kidney length) is shown in Table 5. The models show that the GA is best predicted by the one which incorporates all the five indices; i.e. BPD, HC, AC, FL and FKL respectively. The accuracy of predicting gestational age from these indices was ±4.29 days.

The values of the fetal kidney lengths along with the respective standard deviations for different gestational ages from 20 to 40weeks were related to the predicted gestational age for BPD in weeks (Table 6). This is the normogram of the study.

53 Slope: y= 1.236 + 2.457x

Majority of the observed measurements are clustered about the hypothetical trajectory expected for strongly correlated variables.

Figure 18: Correlation of Biparietal Diameter (BPD) with Gestational age (LMP; weeks).

54 Slope: y= 28.018 + 8.266

Majority of the observed measurements are clustered about the hypothetical trajectory expected for strongly correlated variables.

Figure 19: Correlation of Head Circumference (HC) with Gestational age (LMP; weeks).

55 Slope: y= 9.432x – 24.487

Majority of the observed measurements are clustered about the hypothetical trajectory expected for strongly correlated variables.

Figure 20: Correlation of Abdominal Circumference with Gestational age (LMP; weeks).

56 Slope: y= 2.209x – 8.724

Majority of the observed measurements are clustered about the hypothetical trajectory expected for strongly correlated variables.

Figure 21: Correlation of Femur length with Gestational age (LMP; weeks).

57 Slope: y= 1.040 – 0.535x

Majority of the observed measurements are clustered about the hypothetical trajectory expected for strongly correlated variables.

Figure 22: Correlation of Fetal Kidney Length (FKL) with Gestational age (LMP; weeks).

58

Table 3: Correlation between fetal kidney length, the other standard biometric indices and gestational age (LMP weeks).

LMP (weeks) FKL P-value

BPD 0.95 0.94

< 0.001 HC 0.94 0.93

AC 0.93 0.92 FL 0.97 0.95 FKL 0.96 1 LMP 1 0.96

All the standard biometric indices and the fetal kidney length showed a very significant positive correlation with the gestational age as determined by the LMP.

59

Table 4: Accuracy of gestational age prediction between 20-40 weeks using the fetal biometric indices; including the fetal kidney length.

Dependent variable: LMP; SEpred: Standard error of prediction (days).

Parameter P-value R² SEpred (days)

FL

<0.001 97.3 3.58

FKL

<0.001 94.2 3.62

BPD

<0.001 91.1 4.90

HC

<0.001 88.5 15.99

AC

<0.001 87.7 17.57

60

Table 5: Accuracy of predicting gestational age between 20-40 weeks gestation using various models incorporating different biometric indices (without fetal kidney length).

INDICES REGRESSION EQUATION R² SE

FL,BPD GA=3.63+0.508BPD+0.467FL 93.1 6.36

FL,HC GA=3.719+0.642FL+0.332HC 92.3 6.44

FL,AC GA=5.573+0.623FL+0.348AC 92.2 6.44

FL,FKL GA=1.814+0.172FL+0.823FKL 97.6 5.79

BPD,AC,HC GA=2.276+0.557BPD+0.288AC+0.131HC 92.6 7.41

FL,BPD,AC GA=3.691+0.372FL+0.418BPD+0.189AC 93.4 7.35

BPD,FL,HC GA=3.037+0.425FL+0.416BPD+0.138HC 93.2 7.33

BPD,HC,AC,FL GA=3.315+0.375BPD+0.085HC+0.162AC+0.360FL 93.2 6.33 BPD,FL,HC,AC,FKL GA=1.185+0.121BPD˗0.027AC+0.042HC+0.771FKL+0.091FL 97.7 4.29

61

Table 6: Predicted Fetal Kidney Length measurements at specific menstrual gestational ages; i.e. FKL Normogram for Gestational Age.

LMP (weeks) Mean FKL 95% Confidence Interval Lower Bound Upper Bound

20 20.7056 20.4615 20.9496

21 21.3967 21.2053 21.5881

22 22.1667 21.9460 22.3874

23 23.5217 23.3069 23.7366

24 24.6844 24.5560 24.8129

25 25.1647 25.0816 25.3123

26 25.0647 25.7846 26.1448

27 27.2167 26.9544 27.4790

28 28.6357 28.5175 28.7539

29 29.4431 29.2803 29.6058

30 31.0422 30.8482 31.1843

31 31.3750 31.3362 31.5657

32 32.7112 32.4619 32.9606

33 33.6267 33.4462 33.8071

34 34.3561 34.2262 34.4861

35 35.5589 35.3706 35.7473

36 36.444 36.7518 37.1370

37 38.0585 37.7714 38.3457

38 39.7643 38.5214 40.1346

39 40.8342 39.2140 42.1351

40 41.4167 42.3988 42.6982

62 DISCUSSION

In this study, the fetal kidney length showed a linear increase with advancing gestational age - a weekly increase of 1mm from one successive gestational age to another. This validates the first hypothesis and is in agreement with the findings of Kansaria et al, Konje et al and Kumar et al respectively3^,6^,34. However, there were some slight variations. Although the values for the fetal kidney length obtained in this study were similar to those reported by Konje et al in the United Kingdom6, they were greater than the values obtained by Kansaria et al in Bombay (India)3 for all gestational ages. On the other hand, while the values obtained in this study were higher than those reported by Kumar et al in Uttar Pradesh (India)³⁴ between the 20^th to the 24^th week of gestation;

similar values were observed as from the 26^th week of gestation onwards. A number of reasons could explain these differences. These include number of operators (multiple in their studies versus one operator in this study), type of study (theirs were longitudinal studies while this was a cross-sectional study), quality of ultrasound machine (older versus newer) and racial differences respectively. In this study, all the measurements were taken by one operator, exact measurements were used; i.e. not rounded off to the nearest single figure, the ultrasound machines used were recent models and the patients included in the study are of African descent with body habitus that is different from Asian populations.

A strong correlation was established between the fetal kidney length, gestational age and the other fetal biometric indices; i.e BPD, HC, AC, and FL. This also validates the first hypothesis. The strongest correlation was observed between LMP and the FL; r=0.97; followed by that between LMP and FKL; r=0.96. While the least correlation was exhibited between LMP and AC; r=0.94 (p<0.001).

63

Similar findings were reported by Kumar et al ³⁴ in India. Although Kansaria et al4 in Bombay (India) and Konje et al7 in the United Kingdom also demonstrated a strong correlation between mean kidney length and gestational age in their studies, the most accurate single predictor of gestational age according to their findings was the mean kidney length. This disparity in observations could be explained by the difference in sample sizes of the respective studies. Konje et al and Kansaria et al each had a study population of less than a hundred (fifty and seventy-three respectively)3^,6. Kumar et al on the other hand had a study population of 199³⁴ while this study had over a thousand participants.

This study demonstrated that by measuring fetal kidney length, pregnancies could be dated to within 3.62 days in those presenting late for antenatal booking or in those women who have forgotten their last menstrual period (LMP). This validates the second hypothesis. These findings are similar to those reported by Kansaria et al3 (9.17 days), Konje et al6 (10.29 days) and Kumar et al³⁴ (8.4 days) respectively. On the other hand, the most inaccurate biometric index was abdominal circumference (AC) with a standard error (SE) of 17.57 days in this study, 14.54 days by Konje et al6 and 11.14 days by Kansaria et al3 respectively.

This provides an advantage in those fetuses whose biparietal diameter and/or head circumference cannot be accurately measured because the fetal head is too low6, or the correct plane of measurement cannot be obtained due to abnormal fetal lie²⁹ or where congenital anomalies distorting the fetal skull are present²⁹; e.g. hydrocephalus. In these circumstances therefore, the length of the fetal kidney can be used on its own to provide an estimate of the gestational age.

Models for prediction of gestational age were derived using a combination of the various biometric indices. These models demonstrated that the best gestational age predictor was obtained using the model that incorporated the BPD, HC, AC, FL and FKL with a standard error of prediction (SE) of 4.29 days.

64

This was more accurate than the model that incorporated only four of the biometric indices excluding the fetal kidney length with a standard error of prediction (SE) of 6.33 days. Similar findings were reported in the study by Konje et al6 where a similar model best predicted gestational age (8.48 days) when compared to the other models that did not include the fetal kidney length in combination with others (9.45 days)6.

It has been established that there is no statistical difference between the measurements of the right and left kidney as reported by other authors1^,3^,6^,7^,21. This was also confirmed in this study where no statistical difference was established between measurements of the right and left fetal kidneys;

p>0.34. Therefore, failure to obtain measurements of both kidneys will not negate the use of a single kidney measurement in estimation of gestational age. Although various fetal positions were encountered in the course of this study, manipulations of the transducer and angle of insonation relative to the plane of the kidneys allowed identification in all of the cases. A case where both kidneys could not be measured was not encountered in this study.

65 CONCLUSION

Fetal kidney length showed a linear increase with advancing gestational age and was shown to correlate well with gestational age. A mean increase in length of 1mm per week was observed from one successive gestational age to another among the fetuses studied.

The fetal kidney length is more accurate than the BPD, HC and AC in predicting gestational age but less accurate than the femur length in predicting the gestational age.

The model which best predicted gestational age is that which incorporated the four fetal standard biometric indices (BPD, HC, AC and FL) and the fetal kidney length with a standard error of

±4.29 days. Thus, fetal kidney length can be used as a tool for estimating the gestational age in the late second and third trimesters.

66 LIMITATIONS OF THE STUDY

1. Visualisation of the fetal adrenal gland separate from the kidney before measurement is necessary to prevent errors in measurement. This can be quite challenging due to the similar echogenic characteristics of the two structures and their close proximity to one another. This resulted in prolonged scanning times and this can be uncomfortable for the pregnant women.

2. Due to its nature of being a cross-sectional study, the measurements were one-time observations obtained from different patients at different stages of pregnancy. A longitudinal study where measurements would be obtained from the same group of patients at the different stages of their pregnancies over time was not undertaken due to the low follow up rate in our environment.

67 RECOMMENDATIONS

1. In developing countries such as Nigeria where the literacy level is much lower than what is obtainable in the developed nations, proper menstrual history at antenatal booking is usually a challenge. In addition, most of the patients present in the later part of their pregnancies. Thus, in these cases, fetal kidney length can be used as a reliable tool for estimating the gestational age to increase the accuracy of dating.

2. Radiologists should acquaint themselves with the measurement and sonographic appearances of the fetal kidneys as a routine practice. It has been shown that apart from its application in the assessment of fetal gestational age, it aids in early detection of renal anomalies which are a relatively common occurrence.

3. Further research work should be encouraged to develop a comprehensive normogram for the entire country which should be incorporated into the routine sonographic obstetric evaluation in the second and third trimesters.

68 REFERENCES

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6(7):4990-4993.

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15 Salvesen KÅ. Ultrasound in Pregnancy and non-right handedness: Meta-analysis of Randomised Trials. Ultrasound Obstet Gynecol. 2011; 38: 267-271.

16 Stalberg K, Axelsson O, Haglund B, Hultman CM, Lambe M, Kieler H. Prenatal Ultrasound Exposure and Children’s School Performance at age 15-16: Follow-up of a Randomised Controlled Trial. Ultrasound Obstet Gynecol. 2009; 34: 297-303.

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35 Damen-Elias HAM. Fetal Renal Anomalies: Diagnosis, Management, and Outcome. Intra-observer and Inter-Intra-observer Variability of Fetal Kidney and Adrenal Gland Measurements [Dissertation- PhD]. The Netherlands: Universiteit Utrecht; 2004.

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74 APPENDIX 1

PATIENT INFORMATION

This is to inform you, Mrs/Ms --- that certain information that will be collected during the course of this sonographic examination of your unborn child will be used for a study being carried out by me; Dr Maimuna A. Halliru as part of a research titled “SONOGRAPHIC ESTIMATION OF GESTATIONAL AGE USING FETAL KIDNEY LENGTH IN AMINU KANO TEACHING HOSPITAL KANO, NIGERIA.”

All information gathered from you is strictly for research purposes to the benefit of mankind. In addition, all your personal details will remain confidential and on no account will your identity or any information that can identify you appear in any of the documents related to this study before and after publication.

Please note that your cooperation in this study will not attract any financial compensation.

Your agreement to participate in this study is voluntary and your decision to accept or reject participation will not affect your care. You are free to withdraw consent at any stage either verbally or in writing.

75 APPENDIX II

CONSENT FORM

I --- hereby consent to partake in the study titled; “SONOGRAPHIC ESTIMATION OF GESTATIONAL AGE USING FETAL KIDNEY LENGTH IN AMINU KANO TEACHING HOSPITAL KANO, NIGERIA.” being conducted by Dr Maimuna A. Halliru.

I am aware of the nature of the study and its anticipated benefit to humanity.

I give my consent voluntarily without any inducement and not in any anticipation of financial remuneration or favour.

Date --- Signature ---

76 APPENDIX III

PROFORMA FORM

1. Serial Number: --- 2. Hospital Number: --- 3. Ultrasound Number: --- 4. Age: ---

5. Marital Status: Married ( ) Single ( ) Divorced ( ) Widowed ( ) 6. Parity: Gravida ( ) Para ( ) Alive ( ) Miscarriages ( )

7. LMP: / /

8. Clinical GA: --- Weeks --- Days 9. Clinical Information

 Menstrual History: Regular ( ) Irregular ( )

 Contraceptive Use: Yes ( ) No ( )

 If yes, for how long? Months ( ) Years ( ) 10. Medical History

 Hypertension: ---

 Diabetes Mellitus: ---

 Sickle Cell Disease: --- 11. Ultrasound Findings

 Singleton/Multiple: ---

 Congenital Anomaly: ---

 Fetal Lie and Presentation: ---

 Placenta: i) Location: ---

ii) Grade of Previa if present: ---

77

 Amniotic Fluid Index: ---

12. Fetal Biometry

BIOMETRY MEASUREMENT GESTATIONAL AGE BPD

HC AC FL

FKL (Right) FKL (Left)

 Fetal Heart Rate:

Ultrasound Gestational Age: --- Weeks --- Days

Clinical Gestational Age (from LMP): --- Weeks --- Days

Dr. --- RADIOLOGIST

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