Journal of Cancer Research and Therapeutic Oncology
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Placental Biometric Parameters: The Usefulness of Placental Weight Ratio and Birth/Placental Weight Ratio Percentile Curves for Singleton Gestations as a Function of Gestational age

Rosete Nogueira, MD,PhD Auxiliary*
AFFILIATIONS
School of Medicine, University of Minho, Surgical Sciences Domain Research, Campus de Gualtar, 4710-057, Braga, Portugal
Corresponding author (Address):
Rosete Nogueira, Life and Health Sciences Research Institute (ICVS) / ICVS-3B's, Surgical sciences domain School of Medicine, University of Minho, Campus de Gualtar; 4710-057 Braga, Portugal; E-mail: rosete.nogueira@med.uminho.pt
, Pedro Luís Cardoso, BSc, MSc
AFFILIATIONS
CGC Genetics, Unilabs, Molecular Laboratory, R. Sá da Bandeira, 706, 1º, 4000-431, Porto, Portugal
, Cristina Pace
AFFILIATIONS
Department of Diagnostic and Interventional Radiology, University Hospital Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
, Ana Azevedo, BSc
AFFILIATIONS
CGC Genetics, Unilabs, Embryo-fetal Pathology Laboratory, R. Sá da Bandeira, 706, 1º, 4000-431, Porto, Portugal
, Marcos Gomes, BSc
AFFILIATIONS
CGC Genetics, Unilabs, Embryo-fetal Pathology Laboratory, R. Sá da Bandeira, 706, 1º, 4000-431, Porto, Portugal
, Cláudia Almeida, BSc, MSc
AFFILIATIONS
CGC Genetics, Unilabs, Embryo-fetal Pathology Laboratory, R. Sá da Bandeira, 706, 1º, 4000-431, Porto, Portugal
, Catarina Varela, BSc
AFFILIATIONS
CGC Genetics, Unilabs, Embryo-fetal Pathology Laboratory, R. Sá da Bandeira, 706, 1º, 4000-431, Porto, Portugal
, Ana Cristina Braga, PhD
AFFILIATIONS
Engineering School, University of Minho, Department of Production and Systems, Campus de Gualtar, Braga, Portugal
, Jorge Correia Pinto, MD, PhD
AFFILIATIONS
Life and Health Sciences Research Institute (ICVS), ICVS/3B's - PT Government Associate Laboratory, Campus de Gualtar, 4710-057, Braga/Guimarães, Portugal
Received Date: July 16, 2019Accepted Date: August 27, 2019Published Date: August 29, 2019

Citation:Rosete Nogueira (2019) Placental Biometric Parameters: The Usefulness of Placental Weight Ratio and Birth/Placental Weight Ratio Percentile Curves for Singleton Gestations as a Function of Gestational age. J Clin Anat Pathol 4: 1-15.

Abstract

Objective: To produce reference values for the placental weight (PW), Placental diameters (PDs), Placental thickness (PT), placental weight ratio (PW-R) and birth/placental weight ratio (BPW-R) in singleton gestations as a function of gestational age (GA).

Study Design and Setting: A retrospective 4-years case study of singleton placentas reports between, 1st of January 2014 to 31st of December 2017. The placentas were sent for histopathological diagnosis to Embryofetal Pathology Laboratory, Centro de Genetica Clínica (CGC), Porto, Portugal. In a cohort of singleton placentas, PW, PDs, PT, PW-R, and BPW-R were analyzed to produce percentile curves. Considering the inclusion criteria, 1,951 singleton placentas were selected from a sample of 7,321 placentas. We recorded the PW, PDs, PT, PW-R, and BPW-R between 12th and 41st GA.

Results: PW, PDs, PW-R and BPW-R tables and percentiles curves for singleton placentas across GA were produced.

Conclusions: Placental percentile curves may act as a reference for other populations as well until population-specific curves can be produced. PDs could predict placental volume and could help to estimate the prenatal PW-R and BPW-R.

Keywords: Placental weight; placental diameter; placental weight ratio; birth/placental weight ratio; percentiles; singleton gestation.

Introduction

Recently we have seen an increasing interest on the evaluation of biometric parameters of the placenta and its relation with the obstetric outcome. However, the relative lack of interest in the study of the placenta when compared to the fetal study was responsible for the existence of a great gap in the understanding of the biological significance of the placental lesions related to perinatal and neonatal context [1-5].

Macroscopic placental evaluation in the delivery room may improve a selection of placentas to histopathological study and, on the other hand, allow the evaluation of the placental weight (PW) and consequently the placental weight ratio (PW-R) and birth/placental weight ratio (BPW-R). Knowing these are factors that may be associated with pregnancy complications [1-5].

While birthweight (BW) percentile curves are relatively common in most countries, percentile curves for PW are rare, even in large series of placental studies [6,7]. At present we have available some fetal and placental percentiles curves which the majority refers to gestational age (GA) above 24 weeks [6,7]. However, some of the existing information may be out of date, as documented for the BW percentile curves [6,7]. Thus, the updating of percentile curves and their comparison between regions and even between countries are important to manage the pregnancy risks and to enhance the mother education and healthcare [1-4].

Although additional evidence is needed, the percentile curves are useful in evaluating fetal follow-up and maternal and child diseases. The percentile curves comprehension can optimize a targeted intervention in fetal adverse contexts such as intrauterine growth restriction(IUGR) and maternal diseases such as hypertension and diabetes also.

Objective

To produce gestational age-specific percentile curves for PW, placental diameters (PDs), placental thickness (PT), PW-R and BPW-R.

Material and methods
Sample and Definition

We conducted a retrospective case-study of 7,321 placentas sent to Embryo-fetal Pathology Laboratory, Centro de Genética Clínica (CGC), Unilabs, Porto, Portugal. The specimens had been sent for histopathological examination to confirm or determine suspected or unsuspected lesions that explain the obstetric outcome such as fetal demise and perinatal morbidity and mortality.

We collected information of 4-years placental pathological report performed between 1st of January of 2014 to 31st of December of 2017. The GA range of 12 to 41 weeks. Biometric parameters were collected from placentas and fetal deaths autopsy reports. Also, biometric parameters of newborns were obtained through the information contained in the clinical requisition of the placental pathological study. The registry involved data on maternal age and parity; GA; pathological placental reports; fetal autopsy reports and newborns clinical data. Placental parameters biometry's: PW, placental shape and diameter, umbilical cord length, diameters, and type insertion. Fetal deaths parameters acquired: weight and gender. Newborns parameters: weight and gender. Inclusion criteria: – 1. Known GA – 2. Maternal: i. Portuguese population-based woman; ii. Singleton deliveries ≥ 12 weeks of gestation. – 3. Placental: i. Formalin fixation equal or inferior lesser than 24 hours; ii. Absence of macroscopic lesions before 36th weeks of GA; iii. Macroscopic peripheral parenchymal lesion < 5% at ≥37 weeks of GA. – 4. Fetal deaths: i. Maceration is lesser than 12 hours; – 5. Newborns: i. Known birthweight. Exclusion criteria – 1. Maternal: i. Non-Portuguese woman; ii. Multiple pregnancies; iii. Singleton gestation relating to assisted reproductive technology. iv. Known chronic maternal disease (e.g., diabetes, hypertension with or without preeclampsia).–2. Placental: i. Macroscopic lesions more than 5% at any GA; ii. Gestational trophoblastic diseases; iii. Tumors; iv. Disease processes with high-grade histopathological lesions; v. Hydrops. vi. Incomplete, fragmented or disrupted placenta; vii. Placental curettage.–3. Fetal: i. maceration≥12h; ii. Hydrops; iii. intrauterine growth restriction (IUGR).–4. Newborn: i. Unknown BW; ii. IUGR.

The PW and FW were acquired using a balance GS6202 with measuring range 0.01g-620g – scale 0.01g (serial number 12105085, Kern); a balance MOD 470 with measuring range 0.5g-2,000g – scale 0.1g (serial number 42770096, Kern) and balance MOD 734 with measuring range 0g-20,000g – scale 0.1g (serie 1/1, Seca). The placental measures were acquired with a visual scale linear millmetric graduation ruler. Also, to smallest specimens, a comparative measures study achieved with a two linear scale ruler and a digital Vernier gauge 0-150mm scale Würth® was performed with similar results. BW was achieved in the delivery room care unit.

To produce percentile curves, 1,951 placentas were selected from a sample of 7,321 placental histopathological reports. Corresponding fetal gender, BW and FW registry were analyzed. We exclude non-native Portuguese woman (701); Newborn cases with missing data (846); Maceration traducing fetal demise with retention ≥ 12h (438); congenital abnormality was recorded as: no abnormalities, minor abnormalities, and major abnormalities (e.g., neural tube defects, such as, anencephaly, cranium-rachischisis, exencephaly and holoprosencephaly, skeletal dysplasia; limb body stalk complex). So, major defects were excluded (108); Fetal hydrops, or placental findings suggesting aneuploidy or metabolic storage diseases (306); IUGR (190); Multiple pregnancy (621); Partial hydatidiform moles (14); Extravillous trophoblastic diseases (4); Giant chorioangioma (7); Placental maternal vascular processes (652); Placental fetal vascular processes (314); histopathological pattern consistent with high grade immune / idiopathic inflammatory lesions (257) and infectious inflammatory lesions such as chronic plasma cell villitis (CMV, Parvovirus B19, Herpesvirus, Toxoplasma, listeria) (80) and chronic histiocytic intervillositis (CHI) (36); Other placental processes as massive fibrin deposition and maternal floor infarction (98); Single placenta gestation relating to assisted reproductive pregnancy technology (135); Incomplete, fragmented or disrupted placenta (474); Placenta accreta (37); and Placental curettage associated with retention (52). Knowing that PW increase approximately 5% after formal in fixation and the weight loss is little and most significant in hydropic or edematous placentas [6-9]. Initially, placentas were fixed in formalin for 24 hours. Then, after remoting the capsular membrane and umbilical cord, the PW, PDs and placental thickness (PT) were achieved in accordance with international guidelines. [8-9]. Placental disk dimensions include the measurements of the placenta in three dimensions at manual macroscopic examination in embryofetal pathology laboratory, and were achieved as: The maximum linear dimension (largest diameter = length) and the minimum linear dimension (smallest diameter = width) always acquired through the insertion point and perpendicular to each other. The maximum thickness was acquired in the central two-thirds of the disc, in accordance with international guidelines [8-9]. In addition, newborns were weighted in the delivery room care unit and fetus were weighted in the autopsy room. Placental macroscopic examination, sampling, and classification of placental lesions were performed in accordance with international guidelines [6-9].

All the samples used in the present study were unlinked and unidentified from their donors. Due to the retrospective nature of the study, the Local Ethical Review Committees of the involved institutions and Minho University Medicine School (Braga, Portugal) approved the work and waived the need for written informed consent.

Statistical Analysis

The percentiles curves for PW, PDs, PT, PW-R, and BPW-R were based on the same observations.The statistical analysis was conducted in IBMSPSS Statistics version 25 using the most appropriate tests according to the nature of the variables involved. To evaluate the normality, we used the Q-Q plots due to the sample size.

Results

The final sample was 1,951 singleton placentas. PW, PDs, PT, BPW-R, and PW-R mean, standard deviation (SD), median, minimum and maximum to maternal, placental and fetal or newborn quantitative and qualitative variables are summarized in (Table 1) and (Table 2). Maternal age range from 15 to 48 years. Sex was defined as either: female, male and ambiguous or unknown if the data was missing. So, the gender distribution was female in 818 (47.7%) cases, male in 884 (51.5%) cases and ambiguous in 13 (.8%) cases (Table 2). GA was a key variable for this research and played an integral role in establishing BPW-R and PW-R. For the purpose of this study, GA remained as a continuous integer variable, but only the gestational week was used, not the number of days. According to clinical practice, GA estimation was derived from the first day of the last menstrual period. Otherwise, GA was corrected on the basis of ultrasound measurements that are routinely obtained for all pregnant woman in Portuguese hospitals. Placental weight, Fetal and newborn BW was recorded in grams as a continuous variable.

Measures of interest for this study were PW, PDs [e.g., largest placental diameter (LPD or PD>) smallest placental diameter (SPD or PD< ) and placental thickness (PT)], BW, BPW-R, and PW-R. The t-student test was used to compare the mean value of PW at each GA according to gender and likewise for the BW or FW. According to gender, with the exception of 27 weeks (p = .033), there were no statistically significant differences between mean PW for male and female fetuses (p> .05). These results are summarized in the graph of Figure 1. Also, except for 16 weeks (p = .021) and 40 weeks (p = .018), there were no statistically significant differences between mean BW for male and female fetuses (p> .05). These results are shown in the graph in Figure 2. Taking into account these results, it was decided to draw tables for percentiles, a number of observations, mean and standard deviation, minimum and maximum for the PW, BW (e.g., fetal weight and newborn weight). These results are shown in (Table 3) and (Table 4) respectively. The same analysis was performed to BPW-R and PW-R percentiles as a function of GA. These results are shown in (Table 5) and (Table 6 ) respectively.

Percentiles curves for PW, BW, PBW-R, and PW-R, between 12th and 41st weeks of GA, were produced. These results are shown in (Figure 3), (Figure 4), (Figure 5) and (Figure 6) respectively. An approach to placental volume (PV) was determined using the calculation [LPD x SPD x PT]. So, graphs to evaluate PV – PW, and PDs – PW correspondences were produced. These results are shown in (Figure 7).

To assess whether there was an association between PW and PV a Pearson correlation test was performed to evaluate the linear association between variables. The results obtained are found in the matrix (Table 7). It is verified that there is significant linear association with: Positive Very Strong association between: LPD and SPD (r=.918, p < .01); Positive Strong association between: PW and PV (r=.833, p < .01); PW and LPD (r=.826, p <.01); PW and SPD (r=.829, p < .01); PV and LPD (r=.833, p< .01), and PV and SPD (r=.877, p <.01); Moderate Positive association between: PW and PT (r=.619, p < .01) and PV and PT (r=.621, p < .01); Weak Positive association between: LPD and PT (r=.396, p <.01) and SPD and PT (r=.398, p < .01).

Discussion

The placental examination has been important in documenting a pathophysiological complex process associated with poor obstetric outcomes such as fetal and neonatal morbidity and mortality and chronic diseases in later life [1-5].

Over the years there has been the production of percentile curves for BW as a function of GA to guide physicians and parents about fetal and newborn growth [5-7]. Those mostly charts are restricted to 3rd trimester gestation [5-7]. Also, some of these studies address specific contexts such as fetal gender, parity, and ethnicity [10-12]. Beings a positive association between PW and BW with ethnicity and parity [10-12]. Moreover multiparous increases the odds of having a PW-R≥90th percentile, and the effect is most pronounced in the infants born at ≤32 weeks [10]. Knowing that fetal gender shows association with PW, the categorization into male and female-specific curves is important because male weigh more than female at each GA [11-18]. Unlikely, the present study discloses non-statistically significant differences between gender for PW, FW, and BW, except for the PW at 27 weeks of GA (p=.033) and BW at 25 weeks (p=.021) and 40 weeks (p=.018). This suggest that the association between or BW and gender will not be relevant at early GA.

There is some evidence that the shape and size of the placenta are factors that may be statistically associated with pregnancy complications (e.g, IUGR, reduced fetal movements) and an individual's long-term health [19-24].

Besides PW has been described as an independent predictor of BW and a good predictor for chronic diseases in later life [2,3,11,13,15,17-24]. PW percentile curves are rare and mostly refer to GA ≥ 24 weeks [14-18,21,22]. BPW-R (e.g. the BW over the PW) and PW-R (e.g. PW over the BW) percentile curves were a significant contribution to the literature and medicine practice [14-18,21,22] However, rare population curves to date have looked at an early GA such as 12th weeks or earliest [25].

Although reversed, PW-R percentile curves are more specific to the purpose of the present study see (Figure 5) and ( Figure 6). Also, a significant linear association with a very strong or strong positive association between placental biometries may improve the charaterization of the PW and PV and consequently the placental function evaluation.

Knowing that BPW-R and PW-R are important parameters for the balance between fetal and placental growth and considering the functional reserve capacity of the placenta, those may be the greatest predictors of IUGR and diseases in later life than PW and BW alone [1,12,15-18,21,22]. PW-R appears to reflect differences in growth pattern and placental efficiency and correlates significantly with fetal morbidity and short-term adverse perinatal outcomes also [19-24].

Thus, the existence of a linear correlation between placental measurements and a good association with placental volume demonstrated in the present study, may improve prenatal diagnosis and anticipate measures in specific placental and/or fetal situations to prevent the adverse outcome of pregnancy.

Conclusions

Gestational-age-specific placental percentile curves for PW, BPW-R, and PW-R for singleton delivery between 12th and 41st weeks of gestation are available to liken results between countries and regions. The significant association between placental measurements contributes to the assessment of placental function (related to size and volume) and its implication in fetal growth, assisting clinicians in preventing fetal life risks and improving maternal and child health.

Acknowledgments

This work was developed under the scope of the project NORTE-01-0145-FEDER- 000013 and NORTE-01-0145-FEDER- 000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER), and through the Competitiveness Factors Operational Programme (COMPETE) and by National funds, through the Foundation for Science and Technology (FCT),under the scope of the projectPOCI-01-0145-FEDER-007038.

The authors thank Rute Gonzalez Gomes for her logistic support.

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Tables at a glance
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