|Year : 2021 | Volume
| Issue : 2 | Page : 166-171
A clinicopathologic study of placentae of low birth weight and normal birth weight babies born at a tertiary care center in western India
Manish Sharma1, Jasvinder Kaur Bhatia2, Ajay Malik2
1 Department of Laboratory Medicine, Army Institute of Cardio-Thoracic Sciences, Pune, Maharashtra, India
2 Department of Pathology, Armed Forces Medical College Pune, Maharashtra, India
|Date of Submission||13-Apr-2020|
|Date of Decision||07-Jul-2020|
|Date of Acceptance||22-Aug-2020|
|Date of Web Publication||3-Mar-2021|
Jasvinder Kaur Bhatia
Department of Pathology, Armed Forces Medical College, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Context: Low birth weight (LBW) of newborn is associated with various clinical parameters as well as with placental pathology. Aims: This study aims to assess and compare the clinical parameters and placental pathology in LBW infants with normal infants. Subjects and Methods: Thirty-four placentae of full-term babies weighing <2.5 kg were taken as cases and 34 placentae of newborns weighing more than 2.5 kg were taken as controls. Clinical data parity, maternal age, weight, height, body mass index (BMI), mode of delivery, and period of gestation were collected. Gross examination, placental parameters: attachment of cord, placental dimensions, placental weight, infarction, and hematoma were noted. Sections were studied for accelerated villous maturation (syncytial knots), developmental villous capillary lesion (chorangiosis), acute infectious inflammatory lesions (chorioamnionitis), chronic infectious inflammatory lesions (stromal fibrosis), and other placental processes (massive perivillous fibrin deposition [ MPVFD], fibrinoid necrosis, atherosis, and calcification). Statistical Analysis: Chi-square test and logistic regression were performed on dichotomous variables with SPSS 20 to find association. Quantitative variables were analyzed by Unpaired T-test and Mann–Whitney's test for significance. P < 0.05 was taken as statistically significant. Results: The mean maternal age (26.7 years) was higher (P = 0.039) than controls (24.8 years); mean maternal weight (P = 0.14)], BMI (P = 0.029), and period of gestation (P = 0.0) were lower in cases than in controls. Cases and controls showed significant difference in eccentric attachment of umbilical cord (61.76% vs. 32.35%, [P = 0.015*]). On microscopy cases showed significant MPFD (P = 0.015*). A significantly higher stromal fibrosis (P = 0.028), atherosis (P = 0.024), ST knots (P = 0.012), and chorangiosis (58.82% vs. 26.47% [P = 0.007]) were noted in cases. Conclusions: We conclude that all placentas should be examined thoroughly to look for associated characteristic histomorphologic and gross findings which reflect hypoxia and decreased maternal fetal nutrient transfer.
Keywords: Hypoxia, intrauterine growth restriction, low birth weight, placental pathology
|How to cite this article:|
Sharma M, Bhatia JK, 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. Med J DY Patil Vidyapeeth 2021;14:166-71
|How to cite this URL:|
Sharma M, Bhatia JK, 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. Med J DY Patil Vidyapeeth [serial online] 2021 [cited 2021 Oct 18];14:166-71. Available from: https://www.mjdrdypv.org/text.asp?2021/14/2/166/310705
| Introduction|| |
Low birth weight (LBW) is the cause for two thirds of perinatal mortality. Irrespective of period of gestation, birth weight <2.5 kg is defined as LBW by international consensus. Those born before 37 weeks of gestation are preterm where as those born at term with birth weight < 10th centile are small for gestational age (SGA). Those SGA fetuses have clinical growth restriction are termed a intrauterine growth restriction (IUGR). On the basis of ratio of head measurement to abdomen measurement, IUGR fetuses can be subdivided into two groups. First group has fetuses with both small head and abdomen proportionately small. It is known as symmetrical IUGR. In the second group, the abdominal girth is reduced in comparison to head size. This group is known as asymmetric IUGR.
Fetal growth is largely determined by the availability of nutrients to the fetus. The fetus is at the end of a supply line that ensures delivery of nutrients from the maternal/uterine circulation to the fetus through the placenta. Placental function is pivotal to materno-fetal nutrient and metabolite transfer. We conducted this study to evaluate the clinical features and study gross and histological features of placenta in LBW newborns.,
| Subjects and Methods|| |
This was a case–control prospective study at a tertiary care center conducted over a period of 2 years. Thirty-four placentae where newborns were more than 2.5 kg were taken as controls and cases were taken as placentae of all newborns with birth weight <2.5 kg irrespective of period of gestation, mode of delivery, or sex of fetus. Permission was taken from the Institutional Ethical Committee to conduct the study (AFMC IEC November 2016 dated November 15, 2016).
We excluded placentae of intrauterine death and multiple pregnancy cases as there are other factors responsible for growth restriction in these cases.
Parity of mother, maternal age, maternal weight, height, body mass index (BMI), period of gestation, and mode of delivery was collected from hospital records. The birth weight was taken as weight taken in 1st h after birth.
Placenta was grossly examined before fixation. Its dimensions were recorded. Fetal surface was examined for color and health of membranes. Maternal surface was examined for loss of cotyledons, hemorrhage, calcification, or necrosis. Clots if any were removed. The membranes were examined for staining with meconium, edema, or foul smell and then were trimmed up to the margins of the placentae. Umbilical cords were cut at 5 cm from their insertions. Placentae were then dried with blotting paper and weighed on digital weighing scale. The umbilical cord was examined for true and false knots, Wharton's jelly, hemorrhage, and areas of marked edema. Umbilical cord insertion was recorded as central or eccentric. The distance of attachment of cord was recorded from the two opposite ends of the disc on two axes perpendicular to each other. If the cord was away from the center on either of the axis, it was away from center of mass and therefore recorded as eccentric attachment.
After gross examination, two full thickness sections were taken from midzonal area and two sections from central area of placental disc. One section each was taken from placental and fetal ends of umbilical cord. One section was taken from fetal membranes from point of rupture to attachment at placental margin.
3–5 μ sections were cut from paraffin embedded blocks. These sections were stained with hematoxylin-eosin and following findings were recorded. Two pathologists studied the sections to reduce the interobserver bias. Subjectivity of the assessment of features was minimized using criteria based on the placental classification (incorporating the 2014 Amsterdam placental workshop group criteria) to quantify the histological findings.
Placental vascular processes
Maternal stromal vascular lesions - accelerated villous maturation (syncytial knots)
A total of 100 villi were counted in each section and the number of villi having syncytiotrophoblast with highly condensed chromatin, either dispersed throughout the nucleus or in the form of a dense peripheral ring were noted per 100 villi. The number of villi with syncytial knots per 100 villi observed was recorded.
Fetal stromal vascular lesions - developmental villous capillary lesion (chorangiosis)
Using Altshuler's criteria, chorangiosis was defined as “at least 10 vascular profiles per terminal/intermediate chorionic villus see in 10 chorionic villi per three 10× objective microscopic field in at least 10 areas of 3 or more random cotyledons”. Chorangiosis was recorded as present or absent in the section.
Placental inflammatory-immune processes
Acute infectious inflammatory lesions - chorioamnionitis
The presence of neutrophils in the section from fetal membranes was taken as positive for chorioamnionitis.
Maternal inflammatory response was graded and staged as per diagnostic criteria by Perinatal Section of Society for Pediatric pathology. However, inflammatory response was recorded as present or absent for comparison between cases and controls.
Chronic infectious inflammatory lesions - stromal fibrosis
One hundred villi were counted in each section. Sections with fibrosis of stroma in more than 3 villi per 100 villi count were recorded as positive for stromal fibrosis.
Other placental processes
Massive perivillous fibrin deposition (MPVFD)
Defined as marked increase in perivillous fibrinoid deposition in the intervillous space adjacent to the basal plate with varying degrees of upward extension into the midzonal and subchorionic regions. All the three types namely (1) Classic MPVFD—basal villous encasement by fibrinoid along entire maternal floor and of 3 mm or greater thickness on at least one slide, (2) Borderline MPVFD - involvement of 25%–50% of villi on at least one slide in transmural or nearly transmural distribution, and (3) Transmural MPVFD - - transmural perivillous fibrinoid extension, with encasement of 50% or greater of villi on at least one slide; were marked as positive for MPVFD.,
Following findings not in the placental classification were also studied:
- Fibrinoid necrosis: The presence of fibrin around the villi and the villi showing necrosis in more than 3 villi per 100 villi was recorded as positive for fibrinoid necrosis
- Atherosis: Decidual arteries having vessel wall with mural foamy cells were recorded as positive for atherosis
- Calcification: Basophilic amorphous acellular material present in villi/intervillous space in any of the sections was recorded as positive for calcification.
The statistical analysis was done using Statistical Package for Social Sciences (SPSS) v20, IBM, USA. Chi-square test was performed as test of significance on dichotomous variables. Clinical quantitative variables were divided into parametric and nonparametric based on one-sample Kolmogorov-Smirnov test. Parametric Variables were analyzed by Independent samples test with Levene's test for equality of variances. Nonparametric variables were analyzed by Mann–Whitney's test. Logistic regression was studied on dichotomous variables to find association. P < 0.05 was taken as critical level of significance for all the tests.
| Results|| |
In our study, 34 cases and 34 controls were included. The age of mothers of cases ranged from 19 years to 42 years while those for controls ranged between 19 and 32 years. The maternal weight for cases ranged from 45 kg to 85 kg while for controls ranged between 48 and 84 kg. The maternal height of cases ranged from 122 cm to 170 cm while for controls ranged between 137 cm and 168 cm. The maternal BMI of cases ranged from 17.6 kg/m2 cm to 33.5 kg/m2 while of controls ranged between 19.3 kg/m2 cm and 35.2 kg/m2. The caesarean section rates in cases were 47.06% which was eight times higher than in controls (5.88%). The period of gestation for cases ranged from 24 weeks to 40 weeks while of controls ranged between 36 and 40 weeks.
The difference between mean maternal age of cases and controls was statistically significant (26.7 years vs. 24.8 years, [P = 0.039]) whereas mean weight (58.06 kg vs. 63.71 kg, [P = 0.14]), BMI (23.7 kg/m2 vs. 25.82 kg/m2, [P = 0.029]) and period of gestation (36.08 weeks vs. 39.23 weeks, [P = 0.000]) of cases were lower than controls. However, primiparity of mother had no significant difference in the two groups (55.88% vs. 44.12%, [P = 0.33]).
Gross and histological parameters in normal placentae (controls) and LBW placentae (cases) along with P values for Test of significance are shown in [Table 1]. Statistically significant difference in eccentric attachment of umbilical cord (61.76% vs. 32.35%, [P = 0.015*]) and weight of placental disc (432.65 g vs. 325.912 g, [P = 0.000]) was found between the cases and controls. Gross findings of placentae showing central attachment and eccentric attachment are shown in [Figure 1].
|Table 1: Gross and histological parameters in normal placentae (controls) and LBW placentae (cases) along with P values for test of significance|
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|Figure 1: a) Placenta with central attachment, (b) Placenta with eccentric attachment|
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[Figure 2] and [Figure 3] show the histological features studied.
|Figure 2: (a) Accelerated villous maturation: Increased syncytial knots (H and E, ×400), (b) Developmental villous capillary lesion: Chorangiosis (H and E, ×200), (c) Chronic infectious inflammatory lesions: Stromal fibrosis (H and E, ×200), (d) Massive perivillous fibrin (oid) deposition (maternal floor infarction) (H and E, ×200)|
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|Figure 3: (a) Fibrinoid Necrosis (H and E, ×400), (b) Maternal stromal vascular lesion: Atherosis (H and E, ×400), (c) Calcification-(H and E, ×200), (d) Maternal inflammatory response to amniotic infection (acute chorioamnionitis, maternal Stage 2 Grade 1) (H and E, ×400)|
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Mean number of syncytial knots per 100 villi for cases (50.3 + 19.02) was significantly higher than for controls (39 + 17.0). About 58.82% placentae of cases showed chorangiosis, which was more than that seen in controls (26.47%). 26.47% of cases showed chorioamnionitis of fetal membranes as against 23.53% in controls.
About 58.82% placentae of cases showed stromal fibrosis, which was more than (32.35%) that seen in controls. 50% placentae of cases showed MPVFD, which was higher than controls (17.65%). Fibrinoid necrosis was seen in 55.8% placentae of cases while 23.53% of controls showed fibrinoid necrosis. 20.59% placentae of cases showed atherosis, which was more than that (2.94%) seen in controls. The calcification was noted in 32.35% of the cases. While controls showed calcification in 20.59% placentae, 26.47% placentae of cases showed maternal inflammatory response (chorioamnionitis) which was similar to controls (23.53%). Cases showing chorioamnionitis were graded to reveal Grade 1 response in in 37% and Grade 2 response in 63% placentae. On staging a majority (62%) placentae showed stage 2 response, while 25% showed stage 3 while the rest (13%) showed Stage 1 response. Control placentae had similar findings.
The statistical analysis showed significant difference in syncytial knots (50.3 vs. 39/100 villi [P = 0.012]) and Chorangiosis (58.82% vs. 26.47% [P = 0.007]). Cases showed a significantly higher stromal fibrosis (58.82% vs. 32.35% [P = 0.028]), MPVFD, (50% vs. 17.7%, [P = 0.015]), fibrinoid necrosis (55.8% vs. 23.53% [P = 0.006]) and atherosis (20.59% vs. 2.94% [P = 0.024]). However, chorioamnionitis and calcification showed no significant difference.
| Discussion|| |
Placenta and fetus share a common origin. Besides genetic code and growth potential, they also share the same environment, the uterus, in which they develop in parallel. Fetal nutrition, gas exchanges, and removal of products of catabolism depend on placental function. Any change in placenta during fetal life could affect the development of normal fetus, leading to an impaired perinatal outcome. Thus, anatomopathologic analysis of the placenta becomes very important, either to confirm retrospectively a pathological pregnancy course, and to predict the newborn outcome.
Insufficiency of placenta which is directly related to weight of the placenta accounts for a major cause of IUGR. The present study has studied gross and microscopic features in placenta in cases of LBW babies. We also analyzed the significance of each microscopic feature.
The study has found statistically significant findings in placenta of LBW newborns. Clinically, maternal age of mothers delivering LBW newborns was higher than those delivering NBW newborns while maternal weights were less in mothers delivering LBW newborns.
On gross examination, we found that mean placental weights were also on lower side in LBW newborns at the same time the incidence of eccentric attachment was found on higher side.
The results reported here indicate that a relationship exists between morphological changes in the placentae of IUGR and LBW. On microscopic examination, we found ST knots, chorangiosis, stromal fibrosis, MPVFD, fibrinoid necrosis, and atherosis were significantly higher in LBW placentae whereas calcification and chorioamnionitis showed no significant difference.
In this study, eccentric attachment of umbilical cord was significantly more in cases than controls. Our findings are comparable to Dhabhai and Gupta., Nigam et al. and Kotgirwar et al. have reported eccentric attachment of umbilical cord in LBW in 66.7% and 60% while 0% and 56% of placentae of controls showed eccentric attachment, respectively. Our study, Nigam et al. and Dhabhai et al., show statistically significant difference whereas Kotgirwar et al. did not find a significant difference. Since we have observed eccentricity both in short and long axes, the prevalence of eccentricity in the present study is almost double in both cases and controls and hence our results are comparable to Dhabhai and Gupta., Some studies suggest an association between abnormal and adverse pregnancy outcomes in singleton pregnancies including SGA infants, preterm birth, perinatal death, intrauterine fetal death, and intrapartum complications including emergency cesarean delivery.
The mean placental weight of cases (325.9 + 82 g) was significantly lower (P < 0.05) than the mean placental weight (432.6 + 73.3 g) for controls. Nigam et al., Kotgirwar et al. and Park et al. reported mean placental weight of LBW newborns as 266 g, 281 g and 317 g in cases while 399 g, 573 g, and 475 g in controls, respectively. Our results are comparable to other studies.
We found statistically significant difference (P < 0.05) in mean number of syncytial knots. Nelson have given proof that perivillous fibrin/fibrinoid might be a necessary component of syncytial repair especially in instances of syncytial apoptosis. The results of our study are comparable with Kavita Mardi and Lalita Negi. Our study has found fibrinoid necrosis in 55.8% placentae of LBW newborns (cases) which was statistically significant (P = 0.006).
Kotgirwar et al., Kavita Mardi & Lalita Negi and Günyeli et al. have found the prevalence of perivillous fibrin in 16.7%, 64% and 62% placentas of LBW whereas in 1.8%, 12% and 0% controls respectively, our results as comparable with these studies.
It is believed that chorangiosis is an outcome of low-grade placental hypoxia which is independently associated with risk in pregnancy and poor outcomes. It is not known yet whether it a consequence of chorangiosis by itself or independently related with other placental pathology. Chorangiosis has a negative prognostic significance only when diffuse hypoxic patterns are present in the placenta alongside. In our study, statistically significant (P = 0.007) difference between cases and controls was found. Park et al. studied chorangiosis and found it significantly higher in cases than controls.
We found statistically significant difference in stromal fibrosis (P = 0.028). Kavita Mardi and Lalita Negi, Nigam et al., and Park et al. have found prevalence of massive perivillous fibrin in 56%, 25%, and 31.1% placentae of LBW whereas in 12%, 0%, and 38% controls, respectively. Our results most closely resembling those of Kavita Mardi and Lalita Negi.
Massive perivillous deposition of fibrin is a very consistent finding seen in placenta of LBW newborns. It is also associated with recurrent fetal loss. We studied this major factor and found it in 50% of the placentae of LBW babies. Kavita Mardi and Lalita Negi, Günyeli et al., Kotgirwar et al. and Park et al. have the prevalence of massive perivillous fibrin in 64%, 62%, 16.7%, and 26.7% placentas of LBW whereas in 12%, 0%, 1.8%, and 4.2% controls, respectively. Findings of the present study are comparable to Kavita Mardi and Lalita Negi.
Atherosis in the uteroplacental bed manifests as fibrinoid material in spiral arterioles surrounded by foam cells. It is not specific to preeclamptic placentae and has been seen in LBW placentae. We have found the difference statistically significant (P = 0.024).
| Conclusions|| |
We conclude that all placentas should be examined thoroughly to look for associated histomorphologic and gross findings which ultimately reflect hypoxia and decreased maternofetal nutrient transfer leading to poor outcome in the perinatal period.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]