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

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.


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][2][3][4][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][2][3][4][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][2][3][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.

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 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.

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 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 (  Legend: CI, confidence interval; g, grams; GA, gestational age; F, female; M, male.    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 (

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][2][3][4][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][6][7]. Those mostly charts are restricted to 3rd trimester gestation [5][6][7].
Also, some of these studies address specific contexts such as fetal gender, parity, and ethnicity [10][11][12]. Beings a positive association between PW and BW with ethnicity and parity [10][11][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][12][13][14][15][16][17][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][20][21][22][23][24].
Although reversed, PW-R percentile curves are more specific to the purpose of the present study see ( Figure 5) and (  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][16][17][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][20][21][22][23][24].
Thus, the existence of a linear correlation between placental measurements and a good association with placental vol-ume 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.