From placenta to cradle: Histopathology as a predictor of fetal and neonatal well-being

INTRODUCTION

The placenta is a dynamic organ essential for fetal growth and development. It mediates gas exchange, nutrient transfer, and waste elimination between the mother and fetus. Placental pathologies can disrupt these functions, leading to adverse fetal and neonatal outcomes.^[1] In clinical settings, histopathological examination of the placenta often provides critical insights into perinatal complications^[2] and has good predictive potential in clinical practice.^[3] Placental histopathology is important not only in understanding implantation and early pregnancy survival^[4] but also in giving evidence of insufficiency and its clinical implications.^[5] In addition, placental findings give significant insights into acute chorioamnionitis and funisitis, possible group B streptococcal neonatal sepsis,^[6,7] and may be useful in situations such as preterm premature rupture of membranes.^[8] Studies have also shown associations between placental disorders and conditions such as bronchopulmonary dysplasia and necrotizing enterocolitis in preterm infants, underscoring the necessity for comprehensive placental evaluation.^[9]

Understanding these pathologies is essential for timely diagnosis and management, thereby enhancing maternal-fetal well-being and reducing risks associated with adverse pregnancy outcomes. Research has increasingly highlighted the intricate relationship between placental health and neonatal outcomes, with various pathologies linked to long-term infant development and immediate postnatal complications. As advancements in diagnostic methodologies and a deeper understanding of placental physiology emerge, the potential for optimizing care and outcomes for both mothers and infants remains significant.

This review article aims to synthesize current knowledge on placental lesions, their clinical significance, and their impact on fetal and neonatal health.

PLACENTAL STRUCTURE AND FUNCTION

The placenta comprises two main surfaces: The fetal surface, smooth and amnion-covered, and the maternal surface, which is dull, grayish-red, and divided into cotyledons. Its histological layers include the chorionic plate, basal plate, and intervillous space. Villi, categorized into primary, secondary, and tertiary stages, form the functional units responsible for the exchange between maternal and fetal blood. Any disruption in this architecture can result in compromised placental function, manifesting as pregnancy complications such as intrauterine growth restriction (IUGR), preterm birth, or stillbirth.^[10]

CLASSIFICATION OF PLACENTAL LESIONS

Based on the Amsterdam Placental Workshop Group criteria,^[11] placental lesions are classified into vascular processes, infectious-inflammatory processes, and other processes.

CORRELATION OF SPECIFIC HISTOPATHOLOGIES WITH OUTCOMES

Understanding the correlation between specific placental histopathologies and neonatal outcomes is crucial for improving perinatal care. Various studies have explored these correlations, providing valuable insights into the impact of placental lesions on fetal and neonatal health [Table 1].^[2]

1. Hypoxic-Ischemic Encephalopathy (HIE): Hypoxic conditions often result from abruptio placentae, umbilical cord accidents, or chronic placental malperfusion. Placental examination in HIE cases frequently reveals vascular thrombi and villous infarctions, underscoring the role of placental vascular integrity in fetal oxygenation.^[2]

2. IUGR: Chronic MVM, characterized by villous infarctions and fibrin deposition, is a leading histopathological finding in IUGR cases. The presence of delayed villous maturation further accentuates the growth restriction.^[2]

3. Preterm Birth: Histological chorioamnionitis is a predominant lesion in preterm deliveries. It triggers inflammatory cascades that weaken fetal membranes and precipitate preterm labor. Chronic inflammatory processes, including villitis, are also frequently observed.^[2]

4. Stillbirth and Neonatal Mortality: Placental lesions, including severe vascular malperfusion and massive feto-maternal hemorrhage, are common in stillbirths. Pathologies such as placental abruption and umbilical cord abnormalities further contribute to these outcomes.^[2] Figure 1 explains pathophysiological concept of inflammatory process affecting neonatal outcomes.

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Figure 1:

Inflamatory process in chorioamnionitis and their neonatal impact. GBS: Group B Streptococcus, DAMP: Damage-associated molecular patterns, PROM: Premature rupture of membranes, BPD: Bronchopulmonary dysplasia, RDS: Respiratory distress syndrome, IVH: Intraventricular hemorrhage, COPD: Chronic obstructive pulmonary disease, CNS: Central Nervous System.

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CLINICAL APPLICATIONS OF PLACENTAL HISTOPATHOLOGY

Histopathological examination of the placenta offers a systematic approach to investigating adverse outcomes. CAP guidelines recommend placental evaluation in cases of stillbirth, IUGR, preterm delivery, and neonatal complications such as sepsis.^[18]

INDICATIONS OF PLACENTAL HISTOPATHOLOGY

Table 2 lists the indications for placental submission for histopathological evaluation as per the College of American Pathologists Guidelines [CAP].^[18]

Clinicians, obstetricians and neonatologists should understand the importance of placental examination and include placental examination as part of their routine protocols. The algorithm for placental examination which is given in Figure 2^[18] as per the College of American pathologists [CAP] guidelines.

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Figure 2:

Algorithm for placental examination CAP guidelines (1997). CAP: College of American pathologists.

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MICROSCOPIC EXAMINATION OF PLACENTA SAMPLES

In laboratory settings, placenta samples undergo both macroscopic and microscopic examinations. The macroscopic analysis involves evaluating the maternal surface, umbilical length, presence of hematomas, membrane transparency, and lobulation. Microscopic examination includes assessing for fibrosis, trophoblastic cells, villi, inflammation, and other pathological changes. Data from these assessments are meticulously recorded for further analysis.^[19]

DISCUSSION

The integration of placental histopathology into perinatal care has transformed the understanding and management of pregnancy complications. By offering a microscopic evaluation of placental tissue, this practice uncovers vital insights into the etiology of adverse pregnancy outcomes, shaping interventions for current and future pregnancies.

One pivotal area illuminated by placental histopathology is MVM, a condition arising from defective remodeling of uteroplacental spiral arteries. MVM compromises placental blood flow and is associated with adverse outcomes such as FGR, pre-eclampsia, and stillbirth. Early detection through histopathological criteria outlined by Redline et al. has enabled preventive strategies, including low-dose aspirin prophylaxis and heightened antenatal surveillance, to reduce maternal and fetal risks.^[20]

Infectious-inflammatory lesions are another significant category of placental pathology. These lesions include maternal chorioamnionitis and fetal vasculitis. Maternal chorioamnionitis is characterized by inflammation of the chorion and amnion, often due to bacterial infections ascending from the lower genital tract. This condition is commonly associated with preterm labor and neonatal sepsis. Histopathological examination of the placenta can reveal the presence and extent of inflammation, providing critical information for the management of both the mother and the neonate. Roberts et al.^[16] explored the inflammatory pathways involved in chorioamnionitis and their impact on neonatal health. Fetal vasculitis, characterized by inflammation of fetal blood vessels, can lead to complications such as neonatal sepsis and chronic inflammatory responses.

The predictive value of placental histopathology extends beyond immediate neonatal outcomes, informing the management of future pregnancies. Women with a history of MVM or other placental abnormalities benefit from increased surveillance, early interventions, and tailored antenatal care in subsequent pregnancies. Studies by Norwitz and Fox et al.^[4,5] underscore the importance of identifying recurrent placental pathology to optimize perinatal outcomes.

Despite these advances, significant gaps exist in standardizing placental examination protocols. Variability in histopathological reporting can hinder the consistency and utility of findings. Langston et al.^[18] have emphasized the need for standardized protocols to ensure systematic evaluations and improve inter-institutional comparability. Moreover, rare conditions such as chronic histiocytic intervillositis (CHI) demand further research. CHI, associated with severe FGR and stillbirth, remains poorly understood. Hecht et al.’s exploration of CHI has underscored the pressing need for evidence-based management guidelines.^[17]

Placental pathology findings have implications that extend beyond the neonatal period, offering insights into the child’s long-term health.^[21] Conditions such as IUGR and preterm birth –frequently linked to placental insufficiency – are associated with an increased risk of chronic diseases later in life. Research demonstrates that IUGR predisposes individuals to hypertension, cardiovascular disease, and type 2 diabetes due to fetal programming alterations.^[22]

Similarly, preterm birth correlates with long-term risks such as chronic kidney disease, neurodevelopmental disorders, and respiratory complications. Early identification of at-risk neonates, coupled with targeted interventions, can mitigate these risks and improve long-term outcomes.^[23]

Integrating placental histopathology into routine clinical practice requires collaboration between obstetricians, pathologists, and pediatricians. Multidisciplinary teams can ensure that placental findings are accurately interpreted and appropriately integrated into clinical care. This collaborative approach can facilitate early identification of at-risk pregnancies, timely interventions, and improved neonatal outcomes. In addition, educating healthcare providers about the importance of placental histopathology and its clinical implications is crucial for its successful integration into perinatal care.

Emerging technologies offer promising avenues for enhancing placental diagnostics. Advanced imaging techniques, such as three-dimensional ultrasound and magnetic resonance imaging (MRI), provide detailed insights into placental structure and function. In addition, non-invasive testing of fetal and placental DNA in maternal blood holds potential for early detection of placental pathologies. Machine learning applications in placental imaging are also being explored to refine diagnostic accuracy and accelerate clinical decision-making.

Placental histopathology serves as a cornerstone in elucidating the etiology of adverse fetal and neonatal outcomes. Incorporating comprehensive placental evaluations into perinatal care can significantly enhance prognosis and guide therapeutic interventions.

Future research should focus on refining diagnostic criteria for placental lesions, developing standardized examination protocols, and investigating the underlying mechanisms of rare pathologies. Advancements in imaging techniques and molecular diagnostics hold promise for enhancing the accuracy and utility of placental histopathology. For instance, the use of advanced imaging modalities such as three-dimensional ultrasound and MRI can provide detailed insights into placental structure and function. Similarly, molecular techniques such as genomic and proteomic analysis can uncover the molecular basis of placental pathologies and identify potential therapeutic targets.

CONCLUSION

Integrating placental histopathology into perinatal care provides crucial insights into pregnancy complications and informs the management of future pregnancies. Standardized protocols and further research into rare pathologies are essential to enhance perinatal outcomes and mitigate long-term health risks for the child.