INTRODUCTION:

It is the functional unit of the entire pregnancy. If there is a disease process involving the mother or the foetus, it will cause changes in the placental pathology and influence the normal functioning of the placenta. Defective functioning of the placenta may lead to various complications in the mother and the growing foetus and may cause adverse outcomes of the foetus.¹ This study attempts to co-relate the USG-derived placental thickness with the foetal outcome and establish a relationship between this and the histopathological changes occurring in the placenta.

Whatever stress the placenta undergoes, the same is faced by the foetus in utero. Any pathological event that affects the mother will have similar consequences on both the foetus and the placenta.^2,3 Hence, placental specificities such as placental thickness and the histopathological findings of the placenta must reflect the changes occurring in the foetus during its period of growth and there must be a correlation between this and foetal outcome.

Similarly, macroscopic, and microscopic histopathological findings of the placenta provide pivotal details about the pathological events that occur in the placenta which may influence the normal functioning of the placenta.⁴Hence, it is indeed important to find a correlation between ultrasonographically assessed placental thickness and placental histopathology and to see if they have any role in determining foetal and neonatal outcome. The placenta, an intriguing and intricate organ, performs vital functions throughout a pregnancy. It functions as the fetus's lungs, gut, kidneys, and liver, providing a secure and protective environment for the fetus's development. Moreover, the placenta has significant endocrine effects that help regulate maternal physiology and metabolism.⁵

Studies have explored the connection between placental thickness measured through ultrasound in the third trimester and fetal outcome. The evidence suggests that a thinner placenta may be linked to fetal growth restriction, preterm delivery, low birth weight (LBW), and fetal distress. For instance, a placental thickness of less than 2cm in the third trimester was found to be significantly associated with fetal growth restriction. Women who delivered preterm were found to have a significantly thinner placenta than those who delivered at term. A thinner placenta was also associated with a lower birth weight. Additionally, fetuses with abnormal fetal heart rate patterns were found to have a thinner placenta. However, more research is needed to fully understand the relationship between placental thickness and fetal outcomes and to determine how these findings can be applied in clinical practice. During the third trimester of pregnancy, the thickness of the placenta can be measured using ultrasonography at two different time points: at 32 and 36 weeks of gestation. This non-invasive evaluation can provide valuable information about fetal well-being and can help healthcare providers predict potential complications such as fetal growth restriction, preterm delivery, LBW, and fetal distress. By monitoring changes in placental thickness over time, healthcare providers can adjust their management plans accordingly and take appropriate action to ensure the best possible outcome for both the mother and the baby. It is important to keep in mind, however, that placental thickness should not be the only factor considered when evaluating fetal well-being. A comprehensive assessment should include other factors such as fetal biometry, amniotic fluid volume, and fetal Doppler assessment to ensure that all aspects of fetal development are considered.⁶

The thickness of the placenta is an important factor in the evaluation of fetal well-being during pregnancy. Ultrasonographic assessment of placental thickness has been shown to be a useful tool in predicting potential complications and adverse outcomes in the fetus. A thinner placenta has been associated with fetal growth restriction, preterm delivery, LBW, and fetal distress. Placental thickness can be measured through ultrasonography at different time points during the third trimester, allowing healthcare providers to monitor changes in placental function and take appropriate action to mitigate potential complications.⁷ However, it is important to note that placental thickness should not be the sole factor in predicting fetal outcome, and other factors such as fetal biometry, amniotic fluid volume, and fetal Doppler assessment should also be considered. Ultimately, a comprehensive evaluation of fetal well-being that takes into account multiple factors can help healthcare providers make informed decisions and improve the chances of a positive outcome for both the mother and the baby.⁸

Placental histopathology is the examination of the placental tissue under a microscope to assess any abnormalities or changes that may have occurred during pregnancy.⁹ The placenta is a vital organ that develops in the uterus during pregnancy and plays a crucial role in providing oxygen and nutrients to the growing fetus. Placental histopathology can help identify a wide range of issues, such as infections, inflammation, abnormal cell growth, and blood flow problems. It can also reveal conditions like gestational diabetes, preeclampsia, and fetal distress. Placental histopathology is often performed when there are concerns about fetal growth, preterm labor, or other complications during pregnancy.¹⁰ It is an important tool that can provide valuable information to healthcare providers, allowing them to make more informed decisions about the management of pregnancy and to provide appropriate care for both the mother and the baby.¹¹

MATERIALANDMETHODS:

The study was conducted among antenatal women visiting ANC OPD in KIMS, Karad, Maharashtra. The duration of the study was of two years dated from 1st September 2018 to 31st August 2020.

(a) Selection Basis: Formula used to calculate the selection population:

N=(Z² Σ²)/E² ……………………………………… (1)

Where, Z is standard normal variate at 95% confidence interval=1.96. Σ is mean difference of placental thickness at 32^ndand 36^thweeks of gestation (7.5), E is precision percentage (1%) and N is sample size.

Putting in all the values, N becomes 216.Considering that a few patients will be lost to follow-up, we took 237 patients as our sample size (increase in 10%).

(b) Inclusion Criteria: It includes, all singleton pregnancies irrespective of gravidity, gestational age at enrollment was 30 weeks, women with known LMP and history of regular menstrual cycles, women with an early first trimester dating scan and the age group range between 20-35years.

(c) Exclusion Criteria: It included multiple pregnancies, foetal congenital anomalies, Known cases of maternal systemic and chronic medical diseases like diabetes, hypertension, chronic renal disease, sickle cell anaemia, etc., poor visualization of the placenta and patients with addictions.

(d) Methodology: A prospective observational study of 237 pregnant women from 30 weeks of gestation with a first trimester dating scan, was conducted in the Obstetrics and Gynecology department of a Tertiary Care Hospital. Detailed History of the patients was taken and general, systemic and obstetric examinations were done.

(e) Ultrasonographic Study: Each enrolled patient in this study underwent Ultrasonographic (USG) for measurement of placental thickness at the level of umbilical cord insertion, at 32^ndand 36^thweeks of gestation and were followed up after delivery.At the level of the cord insert point, the thickness of the placenta (measured in mm) was measured. In the thickest part of the placenta, the sonographic cord insertion site is seen as V-shaped hypoechoic regions close to the chorionic plate. Another way to think of it is as linear echoes that are parallel to the placental surface. The mid-placental region between the placental myometrial interface and the echogenic chorionic plate is where the placental thickness was estimated, or a region thereof.¹¹

(f) Parameters: The parameters under consideration were placenta at term, should not be thicker than 45mm. Patients whose placental thickness remains linear with gestational age, are considered as - normal thickness (10^thto 95^thpercentile) group A; thin placenta (<10^thpercentile) group B and thick placenta (>95^thpercentile) group C. Those with thin and thick placentae were closely monitored for the development of IUGR, oligohydramnios, preterm labour, maternal development of PIH, gestational diabetes mellitus¹, etc.

(g) Ethical Statement and Approval: This study was approved by the institutional ethical committee of KIMS(DU), Karad, (Ref. No. KIMSDU/IEC/09/2018). Additionally, a prior written, informed consent of all the patients enrolled in this study was taken before performing the study.

(h) Statistical Analysis: Descriptive and inferential statistical analysis was carried out in present study. The Microsoft Excel 2007 and SPSS 22.0 version software package be used for data entry and analysis. The categorical factors are represented by the number and frequency (%) of cases. The continuous variables be represented by measures of central frequency (like mean) and deviation (SD and range) wherever appropriate. Statistical analysis was done by unpaired student’s t-test, chi-square test and Univariate analysis of variance. P-value <0.05 was considered as statistically significant.

RESULTS:

The present study was conducted among 237 women to study the relationship of ultra-sonographically assessed placental thickness in the third trimester with foetal outcome and its correlation with placental pathology. Observations of the study were presented in following tables.

Table 1: Distribution of study cases by age

Age	Cases	Percentage (%)
20-24 years	101	42.6
25-29 years	115	48.5
30-35 years	21	8.9
Total	237	100.0

The Table 1 shows the distribution of cases by age group and the corresponding percentages. Among the cases analyzed, the largest group was women aged 25-29 years, which accounted for 48.5% of the total. Women aged 20-24 years comprised the second largest group, accounting for 42.6% of the cases. The smallest group was women aged 30-35 years, which represented only 8.9% of the cases analyzed.

Table 2: Distribution of cases according to parity

Parity	Cases	Percentage (%)
Prime para	178	75.1
2^nd para	35	14.8
3^rd para or more	24	10.1
Total	237	100.0

The Table 2 presents information on the number of cases analyzed by parity and the corresponding percentages. The majority of cases were prim parous women, accounting for 75.1% of the total. The second largest group was women who had previously given birth once, accounting for 14.8% of the cases. Women who had given birth three times or more represented the smallest group, accounting for only 10.1% of the cases analyzed. In total, there were 237 cases analyzed, with each case falling into one of the three parity categories.

Table 3: Placental thickness at 32^ndweek and 36^thweek

Parameters	Gestational Age
Parameters	32^nd week (mm)	36^th week (mm)
Cases	237	227*
Placental Thickness - Mean	33.50	35.8mm
Standard Deviation	1.78mm	2.28mm
10th Percentile	29.8mm	31.0mm
95th Percentile	35.7mm	39.9mm

The Table 3 presents data on the gestational age of the cases analyzed, specifically at the 32nd and 36th weeks of pregnancy, and their corresponding placental thickness measurements. The total number of cases analyzed was 237 at the 32nd week, and 227 cases at the 36th week. At the 32nd week, the mean placental thickness was 33.50mm with a standard deviation of 1.78mm. The 10th percentile of placental thickness was 29.8mm, while the 95th percentile was 35.7mm. At the 36th week, the mean placental thickness was 35.8mm with a standard deviation of 2.28mm. The 10th percentile of placental thickness was 31.0mm, while the 95th percentile was 39.9mm.

Table 4: Cases according to 95^thand 10^thpercentile of mean placental thickness at 32^ndweek and 36^thweek

Placental Thickness	Criteria for categories	Women	(%)
32 Week Placental Thickness
29.7mm or less (A)	< 10^th percentile	47	19.8
29.8mm-35.7mm (B)	Between 10^thto 95^th percentile	154	65.0
35.8mm or more (C)	> 95^th percentile	36	15.2
Total		237	100.0
36 Week Placental Thickness
30.9mm or less (A)	< 10^th percentile	46	20.3
31mm-39.9mm (B)	Between 10^thto 95^th percentile	158	69.6
40mm or more (C)	> 95^th percentile	23	10.1
Total		227	100

The categories according to placental thickness at 32nd week and 36th week are presented in Table 4. At 32nd week, cases less than 10th percentile (A) and more than 95th percentile (C) were 19.8% and 15.2% respectively. Cases in between were 65% (B). At 36th week, cases less than 10th percentile (A) and more than 95th percentile (C) were 20.3% and 10.1% respectively. Cases in between were 69.6% (B).

Table 5: Complication during pregnancy in the study participants

Complication During pregnancy	Cases	%
Total PIH PIH alone 23 9.7% PIH + GDM 4 1.7% PIH + IUGR 20 8.3% PIH + Oligohydramnios 7 3.0% PIH + Oligo + IUGR 5 2.1% PIH + severe Anemia 3 1.3%	62	26.1
GDM alone	28	11.8
IUGR + Oligohydramnios	8	3.4
IUGR alone	20	8.3
Oligohydramnios alone	5	2.1
Rh Iso-immunization	1	0.4
No complication	113	47.7

Various complication occurred during antenatal period of selected women for the study are presented in table 5. PIH was the most common complication during ANC period found in 26% cases. GDM was found in 32 cases. However, nearly half of the women there was no complication during pregnancy.

Table 6: Macroscopic characteristics of study placenta

Macroscopic Characteristics	No. of Placenta	Percentage
Placental shape:
Round	182	76.8
Ovale	55	23.2
Insertion of cord:
Central	213	89.9
Eccentric	24	10.1
Placental weight (g)	517.65	178.72
Placental diameter (cm)	16.42	4.09
Placental thickness at centre	2.52	0.94

The information provided in Table 6 represents the macroscopic characteristics of 237 placentas. The majority of placentas had a round shape, with 182 cases (76.8%), while 55 cases (23.2%) had an oval shape. The insertion of the cord was mostly central, with 213 cases (89.9%), while 24 cases (10.1%) had an eccentric insertion. The average placental weight was 517.65 grams, with a standard deviation of 178.72grams. The average placental diameter was 16.42cm, with a standard deviation of 4.09cm. The average placental thickness at the center was 2.52cm, with a standard deviation of 0.94cm.

DISCUSSION:

The placenta is a vital organ that performs essential metabolic, endocrine, and immunological functions. It serves as a protective barrier for the fetus by guarding against infections and harmful substances while also providing respiratory and nutritional support. A healthy placenta with normal structure and function is crucial for proper fetal growth and development.^4-6 Measuring placental thickness through ultrasound is a straightforward way to assess placental size. Additionally, placental histopathology can provide valuable information on changes that occurred during the antenatal period.¹

Patients with thin placenta at 32 weeks of gestation experienced higher rates of complications such as pre-eclampsia (53%), intrauterine growth restriction (27.6%), and oligohydramnios (6%) compared to those with normal placental thickness (20%, 6.4%, and 1% respectively). Patients with thick placenta at 36 weeks of gestation had a significantly higher rate of gestational diabetes mellitus (42.6%) than those with normal placental thickness (6.4%).¹³ Patients with normal placental thickness at 32 weeks of gestation had a lower incidence of complications (64%) than those with thin (6%) or thick (27%) placenta. Patients with thin placenta at 36 weeks of gestation had significantly higher rates of complications such as pre-eclampsia (58.6%), intrauterine growth restriction (15%), and oligohydramnios (6%) compared to those with normal placental thickness (16%, 9%, and 0% respectively). Patients with thick placenta at 36 weeks of gestation had a higher incidence of gestational diabetes mellitus (39%) than those with normal placental thickness (7%). Patients with normal placental thickness at 36 weeks of gestation had a lower incidence of complications (66%) than those with thin (8%) or thick (17%) placenta.^1,14

The study shows that there is a significant decrease in the rate of Cesarean section (CS) in cases with normal placental thickness at both the 32^nd and 36^th weeks of gestation (p<0.01). This suggests that there is an increased likelihood of CS with either thin or thick placenta at the 32nd week, and with either thick or thin placenta at the 36th week. The study revealed that calcification was the most common microscopic finding in 161 of the placentas analyzed, followed by vessel wall thickening and fibrinoid necrosis, which were found in 105 cases each. Calcification was observed exclusively in placentas aged 37 weeks or older, whereas vessel wall thickening and fibrinoid necrosis were found in placentas of all ages. Infarction was also present in placentas of all age categories.⁸ Among LBW babies with a birth weight below 2.5kg, calcification and fibrinoid necrosis were common findings, present in 48% and 30% of the placentas, respectively. Among babies with normal birth weight, calcification was found in 35% of the placentas, while vessel wall thickening and fibrinoid necrosis were found in 91% and 23% of the placentas, respectively. In over-weighted babies, syncytial knots and vessel wall thickening were observed in four cases each.^15,16. Consequently, at the 32nd week, but not at the 36th week, lower placental thickness is related with a poor APGAR score at 5 minutes. Lower placental thickness at weeks 32 and 36 is linked to a greater incidence of NICU admissions.¹⁷

Gupta & Khajuria¹⁸ conducted a study that revealed a higher occurrence of fibrinoid deposition, syncytial knots, and placental infarction in placentas of IUGR infants when compared to controls. This finding was also reported by Aagaard.¹⁹The form of the placenta changed from oval to spherical in more than three fourths of the cases. Cord insertion is central in about 90% of placentas. The average placenta weighed 517.65 gm, had a diameter of 16.42cm, and a thickness at the centre of 2.52cm.

CONCLUSIONS:

According to Kotgirwar et al.'s study, thin placental thickness (below 10th percentile) is linked with poor neonatal outcomes, such as low birth weight (<2.5 kg), low APGAR scores (<7 at 5 minutes), and higher NICU admissions. Additionally, thin placental thickness is linked with a higher risk of developing Pre-Eclampsia, IUGR, and Oligo Hydramnios. Conversely, thick placental thickness (above 95th percentile) is linked with a higher risk of developing GDM and increased NICU admissions. Both thin and thick placentae are linked with a higher rate of C-sections. Infarction is more common in thin placentae, while Syncytial Knots are more commonly seen in thick placentae. Vessel wall thickening is seen in both thin and thick placentae and is associated with poor neonatal outcomes. Vessel wall thickening is more commonly seen in babies with IUGR, while Syncytial knots are more commonly seen in babies with Macrosomia. Fibrinoid necrosis and calcifications are seen in the majority of babies irrespective of their outcome. Vessel wall thickening is associated with the maximum number of NICU admissions. Thus, measuring placental thickness ultrasonographically in the third trimester is a simple and useful method to identify high-risk pregnancies. Certain placental histological features like vessel wall thickening and infarction are associated with abnormal fetal and neonatal events. Placenta, being a readily accessible specimen, assists in identifying the aetiopathology of pregnancy complications.

REFERENCES:

1. Saha S. et al. Histologic and morphometric study of human placenta in gestational diabetes mellitus. Histologic and morphometric study of human placenta in gestational diabetes mellitus. Italian Journal of Anatomy and Embryology. 2014; 119(1): 1-9.

2. BaGhel P. et al. Correlation of placental thickness estimated by ultrasonography with gestational age and fetal outcome. Indian Journal of Neonatal Medicine and Research. 2015; 3(3): 19-24.

3. Patil S. et al. Inflammatory markers in cord blood for early diagnosis of neonatal sepsis. Research Journal of Pharmacy and Technology. 2023; 16(6): 2905-0. doi: 10.52711/0974-360X.2023.00479

4. Ravishankar S. and Redline RW. What obstetricians need to know about placental pathology. Obstetrics and Gynecology Clinics. 2020; 47(1): 29-48.

5. Burton GJ and Jauniaux E. What is the placenta? American journal of obstetrics and gynecology. 2015; 213(4): S6-e1.

6. RedlineRW.Placental pathology is necessary to understand common pregnancy complications and achieve an improved taxonomy of obstetrical disease. American Journal of Obstetrics and Gynecology. 2023; 228(2): 187-202.

7. Lee AJ, Bethune M. and Hiscock RJ. Placental thickness in the second trimester: a pilot study to determine the normal range. Journal of Ultrasound in Medicine. 2012; 31(2):213-218.

8. Durnwald C. and Mercer B. Ultrasonographic estimation of placental thickness with advancing gestational age. American Journal of Obstetrics and Gynecology. 2004; 191(6): S178.

9. Elchalal U.Sonographically thick placenta: a marker for increased perinatal risk—a prospective cross-sectional study. Placenta. 2000; 21(2-3): 268-272.

10. Balakrishnan, M. and Virudachalam T. Placental thickness: a sonographic parameter for estimation of gestational age. International Journal of Reproduction, Contraception, Obstetrics and Gynecology. 2016; 5(12): 4377-4382.

11. Effendi M et al. Association between first-trimester placental volume and birth weight. Placenta. 014; 35(2): 99-102.

12. Haretha A. Study of correlation of placental morphology with morphometrical features of fetus in high-risk pregnancy (Doctoral dissertation, Trichy SRM Medical College Hospital and Research Centre, Trichy. 2020.

13. Salmani D et al. Study of structural changes in placenta in pregnancy-induced hypertension. Journal of Natural Science, Biology and Medicine. 2014; 5(2): 352.

14. Soni RB and Nair S. Study of histological changes in placenta of anemic mothers. LAP Lambert Academic Publishing. 2019.

15. Siva Sree RangaMK. Morphological and histological variations of human placenta in hypertensive disorders of pregnancy. International Journal of Anatomy and Research. 2017; 5(1): 3591-98.

16. Sharma M, Bhatia JK and Malik A. A clinicopathologic study of placentae of low birth weight and normal birth weight babies born at a tertiary care center in western India. Medical Journal of Dr. DY Patil University. 2021; 14(2), 166-171.

17. Gupta N. and Khajuria A. Histomorphological features of placenta in pregnancy complicated with intrauterine growth retardation. JK Science. 2016; 18(1): 21.

18. Aagaard KM. Author response to comment on “the placenta harbors a unique microbiome”. Science Translational Medicine. 2014; 6(254), 254lr3-254lr3.

Received on 19.11.2023 Modified on 24.12.2023

Research J. Pharm. and Tech 2024; 17(2):746-750.

DOI: 10.52711/0974-360X.2024.00116

Digvijay Kadam¹*, Yamini Patil², R. P. Patange³, Supriya Patil⁴,

Shiju Sebastian⁵, Ravindra Jarag⁶

MATERIALANDMETHODS:

RESULTS:

REFERENCES:

Digvijay Kadam1*, Yamini Patil2, R. P. Patange3, Supriya Patil4,

Shiju Sebastian5, Ravindra Jarag6

MATERIALANDMETHODS:

RESULTS:

REFERENCES:

Digvijay Kadam¹*, Yamini Patil², R. P. Patange³, Supriya Patil⁴,

Shiju Sebastian⁵, Ravindra Jarag⁶