{"id":56155,"date":"2024-03-20T11:28:32","date_gmt":"2024-03-20T11:28:32","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=56155"},"modified":"2024-04-01T19:13:41","modified_gmt":"2024-04-01T19:13:41","slug":"association-between-cord-blood-placental-growth-factor-level-fetal-doppler-parameters-and-neonatal-growth-measures","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no1\/association-between-cord-blood-placental-growth-factor-level-fetal-doppler-parameters-and-neonatal-growth-measures\/","title":{"rendered":"Association Between Cord Blood Placental Growth Factor Level, Fetal Doppler Parameters and Neonatal Growth Measures"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Among the\nmost complicated fetal organs that achieves pleiotropic effects over the fetal\ngrowth is the placenta. It disconnects the maternal circulation from the fetal\ncirculation, with which it is in touch via<\/em> various surfaces, i.e. the\nsyncytiotrophoblast presents the placenta to the maternal circulation and the\nendothelium is in touch with the fetal blood 1<\/sup>. <\/p>\n\n\n\n

Early in the\npregnancy, the development of placental vascularity starts and undergoes modifications\nthroughout gestation. On the maternal aspect, the circulation of the\nuteroplacenta is stabilized by the termination of the first trimester 2<\/sup>.\nOn the fetal part, the initial villi of the placenta start to evolve at\nthirteen\u2019s day of conception, and the vascularization of the fetoplacental villi\nstarts at twenty one\u2019s day of conception 3<\/sup>. The adaptation of\nmaternal vascularization comprises modulating of the spiral arteries of the\nuterus by invasive trophoblasts derived from fetus to permit a reduction in\nblood flow resistance into the placental intervillous space 4<\/sup>. So\nthe placental vasculature growth and function are fundamental to reinforce the development\nof the uterus. Vasculogenesis, the de novo consistence of blood vessels and\nangiogenesis, the diverging and modulating of the presenting vasculature, intercede\nplacental villi expansion and maturation, forming the materno-fetal interface 5<\/sup>.<\/p>\n\n\n\n

Placental\nGrowth Factor (PlGF) is mostly implicated in the angiopoiesis of the placental\nchorion and the preservation of healthy growth and development of the placenta.\nPlGF binds primarily to the Flt1 (soluble fms-like tyrosine kinase-1) receptor\nand remodels spiral arteries to allow for sufficient blood supply to the\nplacenta 6<\/sup>. PlGF is primarily synthesized in the placenta and is\nalso produced from umbilical vein endothelial cells 7<\/sup>.\nInterestingly, PlGF has been reported to be expressed in cord blood 8<\/sup>.\nMoreover, Makrydimas et al. 9<\/sup> observed that the human amniotic fluid\nof 7-9 week of gestation has a concentration of PlGF about half that of matched\nmaternal serum. Over midgestation, PlGF and Vascular Endothelial Growth Factor\n(VEGF) showed enhanced levels in amniotic fluid but VEGF revealed a 6-fold higher\nlevel than PlGF 10<\/sup>.<\/strong><\/p>\n\n\n\n

PlGFs participate\nto the fetoplacental circulation development which starts in early gestation\nand evolves all over pregnancy.  Fetal\nsize has been shown to be affected by the fetoplacental circulatory system 11<\/sup>.\nUnluckily, at the end of pregnancy no maternal PlGF levels were detectable and throughout\npregnancy, the PlGF attains its high level about thirty one\u2019s week of conception,\nthen it turns down 12<\/sup>. Of note, around the ninteen weeks of conception the\nlevels of maternal PlGF are approaching with its level to that of the time of\ndelivery. Interestingly, a 10-fold difference between maternal and fetal\ncirculation regarding P1GF levels at the time of delivery with no significant\ncorrelation between them 13<\/sup>.<\/p>\n\n\n\n

Doppler ultrasound\nis utilized to determine the blood flow of the umbilical artery (UA) and fetal\nmiddle cerebral artery (MCA) 14<\/sup>. The cerebroplacental ratio (CPR) is\nmeasured by the pulsatility index (PI), that is applied to assess the oxygenation\nof the fetus 15<\/sup>. In the third trimester, aberration of Doppler\nfindings is usually accompanied by adverse perinatal outcome. Almost all of the\nclinical research works, on the utilization of Doppler parameters, have been concerned\nwith the estimation of small-for-gestational-age (SGA) fetuses, who are at high\nthreat for unfavorable perinatal consequences16<\/sup>.<\/p>\n\n\n\n

 Up to our knowledge, the focus of most studies was on maternal PlGF\nrather than the fetal P1GF, thus the purpose of the current approach was to appraise\nthe interrelation between fetal PlGF, fetal Doppler parameters, gestational age\nas well as neonatal growth parameters assessed by birth weight, birth length,\nhead circumference and mid arm circumference.<\/p>\n\n\n\n

Subjects and methods<\/strong><\/strong><\/p>\n\n\n\n

This cross-sectional investigation was performed\non 50 pregnant women in their third trimester and their newborns. Pregnant\nwomen were selected randomly from attendees at Al-Galaa Maternity Educational\nHospital throughout the time frame from August 2022 to September 2022. The\ninclusion criteria comprised pregnant mothers with age range from 18 and 35\nyears, experiencing their first pregnancy, with a single full term child (>\n37weeks) and the expected mode of delivery was normal vaginal or cesarean\nsection. Exclusion criteria included pregnant mothers with age more than 35\nyears, multiparity, diabetic and those suffering from preeclampsia,\nantiphospholipid syndrome, connective tissue diseases, chronic infections, as\nwell as those who engaged in alcoholism or smoking throughout pregnancy and\nthose with any birth complications involving perinatal asphyxia. <\/p>\n\n\n\n

The present investigation acted in\naccordance with the guidelines of the Committee of ethics for Medical Research\nof the National Research Centre(Code No. 3416072022). After explaining\nthe background, objectives and advantages of the research, formal written agreement\nto participate in the study was taken from all candidates who included in this approach.\nAlso, the informed consent was written by the mothers on the authority of their\nneonates who were incorporated in the research. <\/p>\n\n\n\n

-All the pregnant women were submitted to\nthe full history taking, general and obstetric examination, determining gestational\nage estimated by last menstrual period (LMP) and assured by assessment of crown-rump\nlength at 11\u201313 weeks, establishing the lack of physical deformation of the\nfetus or any genetic situation by ultrasound examination performed during the previous\nperiod of antenatal follow up. <\/p>\n\n\n\n

–<\/strong>Routine third trimester ultrasound examination\nwas done; fetal biometrics and doppler studies for candidates > 37 weeks were\ndone by a consultant via<\/em> utilizing sonography device GE Voluson P8 with\nRAB 2-6 RS Real-time convex transducer 2\u20135 MHZ (Chicago, IL, USA). The following items\nof sonography were determined: estimated fetal weight (EFW) which was quantified\nin an automated manner according to the formula of Hadlock\u2019s, mean umbilical\narterial pulsatility index (UAPI) and mean middle cerebral artery pulsatility\nindex (MCAPI). Based on the International Society of Ultrasound in Obstetrics\nand Gynecology (ISUOG) instructions in 2010, the subsequent sonographic items\nwere employed to determine fetal weight and size; biparietal diameter (BPD),\nhead circumference (HC), abdominal circumference (AC), and femur diaphysis\nlength (FDL), where Astraia software (copyright 2000\u20112009, version 1.20.0 Build 139) was used for entering data\nand generating reports.<\/p>\n\n\n\n

\u2013 Umbilical artery doppler: A free-floating cord was estimated, and the sample gate volume was placed over it, measuring 1 cm (two-third over the artery and one-third over the vein). The angle between the ultrasound beam and the direction of blood flow was maintained as close as possible to 0\u00b0. Measurement of 3\u20116 waves in the image must avoid any fetal or breathing movements throughout the measurement.<\/p>\n\n\n\n

The optimum method of MCA Doppler assessment was as follows.17  <\/strong><\/sup><\/p>\n\n\n\n

Brain axial section measurement (including thalami and sphenoid wings) and magnified.<\/p>\n\n\n\n

Using of color flow mapping to recognize the circle of Willis and the proximal MCA<\/p>\n\n\n\n

Placing of the pulse-wave Doppler gate at the proximal third of the MCA, close to the origin in the carotid artery.<\/p>\n\n\n\n

The angle between the ultrasound beam and the direction of blood flow must be maintained as close as possible to 0\u00b0.<\/p>\n\n\n\n

Recording of at least three to 10 successive waveforms.<\/p>\n\n\n\n

Auto trace measurement should be used to calculate PI.<\/p>\n\n\n\n

The detection of abnormal fetal blood\nflow was established by identifying diastolic block or reverse flow in the\numbilical artery, as well as observing signs of centralization in fetal\ncirculation, which included the increased resistance in the umbilical artery\nand\/or the reduced resistance in the middle cerebral artery. Furthermore, the mode\nof delivery was evaluated to emphasize fetal distress as a crucial indicator\nfor choosing the optimum delivery methods like vacuum extraction, forceps\ndelivery, or cesarean section.<\/p>\n\n\n\n

About 3ml blood of\numbilical cord of the pregnant women was withdrawn, before placental separation.\nThis collection was carried out from a portion of the umbilical cord that was\npromptly clamped and separated during delivery. The collected blood was then placed\ninto plain tubes. Then the blood specimens were centrifuged under cooling at\n1800 x g to isolate sera that were maintained at \u2013 70\u00b0C until analysis. This\nincluded cord blood placental growth factor (PlGF) that was estimated by\nenzyme-linked immunosorbent assay (ELISA) commercial kit according to operating\ninstructions.<\/p>\n\n\n\n

The clinical assessments for all newborns,\nincluding chest, abdomen, heart, and central nervous system examination were\nperformed by pediatrician. Also, the anthropometric measurements of the\nnewborns were assessed prior breast feeding started. The weight of the newborns\nin kilograms was taken without diapers utilizing a digital electronic scale\n(Laka) designed for infants. The length of each newborn (in centimeters) was estimated\nin the supine situation, utilizing a stadiometer (Seca 416) consists of a fixed\nheadboard and a movable foot board. Circumferences of the head and mid upper\narm circumferences (in centimeters) were also estimated by inelastic tape 18<\/sup>.<\/p>\n\n\n\n

Statistics<\/strong><\/p>\n\n\n\n

Data analysis was performed utilizing\nthe SPSS statistical package software for windows version 26 (SPSS Inc,\nPennsylvania, USA). Quantitative analyses were expressed as Mean \u00b1 Standard\ndeviation (SD). Qualitative data were illustrated as frequency and percentage.\nNon-parametric analyses was  presented by\nmedian and range. The analysis of data was done to examine the statistical\nsignificant difference between groups; differences between parametric variables\nwere established using 2-tailed unpaired t-test. Pearson\u2019s correlation\ncoefficients were applied to assess correlations between the data displaying\nparametric distribution. Multiple linear regression analysis for PlGF as a\ndependent factor with the infant anthropometric measurements as predictor\nfactors (Stepwise regression) was performed. P value < 0.05 was accounted\nsignificant difference and P < 0.005 was counted highly significant\ndifference, at a confidence interval of 95%.<\/p>\n\n\n\n

Results<\/strong><\/p>\n\n\n\n

Table (1) shows the correlation between fetal doppler parameters (UAPI, MCAPI, EFW) and PlGF.  UA PI showed significant negative correlation with neonatal weight and PlGF. (P<0.001). Whereas UA PI showed insignificant negative correlation with MCA PI and EFW (P>0.01). MCA PI and EFW showed insignificant positive correlation with neonatal weight and PlGF(P>0.01). MCAPI showed insignificant negative correlation with EFW and UA PI (P>0.01). EFW showed insignificant negative correlation with MCA PI and UA PI (P>0.01).<\/p>\n\n\n\n

Table (2) shows the anthropometric data and PlGF level in cord blood of the studied neonates. Also, the gestational age was included in Table (2).  The level of cord blood PlGF ranged from 102.33\u00b1173.33 pg\/ml with an average value of 142.67\u00b117.93. The gestational age of the participants ranged from 32 to 39 weeks with the mean value of 36.8\u00b12.00.<\/p>\n\n\n\n

Table (3) shows correlation between all the studied neonatal anthropometric parameters, gestational age and PlGF level in cord blood. The findings detonated there is a significant positive correlation between gestational age (GA) and the neonatal anthropometric measurements including mid arm circumference (MAC), head circumference, weight, length, weight Z score, length Z score, head Z score, weight to length (W\/L) and weight to length Z score (W\/L Z Score). Also, significant positive correlation between PlGF and gestational age as well as the neonatal anthropometric measurements were found except head Z Score.<\/p>\n\n\n\n

Table (4) represents multiple linear regression analysis for PlGF with UA PI and neonatal weight. Results indicated that UA PI and neonatal weight are significant predictors for fetal PlGF (P<0.001).<\/p>\n\n\n\n

Table 1: Correlation between fetal doppler parameters (UAPI, MCAPI, EFW) and cord blood PlGF level <\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

 <\/p>\n<\/td>\n

\n

PlGF<\/strong><\/p>\n<\/td>\n

\n

Neonatal weight<\/strong><\/p>\n<\/td>\n

\n

Fetal doppler parameters<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

MCA PI<\/strong><\/p>\n<\/td>\n

\n

EFW<\/strong><\/p>\n<\/td>\n

\n

UA PI<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

MCA PI<\/strong><\/p>\n<\/td>\n

\n

Pearson Correlation<\/p>\n<\/td>\n

\n

0.414<\/p>\n<\/td>\n

\n

0.408<\/p>\n<\/td>\n

\n

1<\/p>\n<\/td>\n

\n

-0.184<\/p>\n<\/td>\n

\n

-0.406<\/p>\n<\/td>\n<\/tr>\n

\n

Sig. (2-tailed)<\/p>\n<\/td>\n

\n

0.070<\/p>\n<\/td>\n

\n

0.074<\/p>\n<\/td>\n

\n

0.437<\/p>\n<\/td>\n

\n

0.075<\/p>\n<\/td>\n<\/tr>\n

\n

EFW<\/strong><\/p>\n<\/td>\n

\n

Pearson Correlation<\/p>\n<\/td>\n

\n

0.261<\/p>\n<\/td>\n

\n

0.247<\/p>\n<\/td>\n

\n

-0.184<\/p>\n<\/td>\n

\n

1<\/p>\n<\/td>\n

\n

-0.166<\/p>\n<\/td>\n<\/tr>\n

\n

Sig. (2-tailed)<\/p>\n<\/td>\n

\n

0.266<\/p>\n<\/td>\n

\n

0.294<\/p>\n<\/td>\n

\n

0.437<\/p>\n<\/td>\n

\n

0.484<\/p>\n<\/td>\n<\/tr>\n

\n

UA PI<\/strong><\/p>\n<\/td>\n

\n

Pearson Correlation<\/p>\n<\/td>\n

\n

-0.933**<\/sup><\/p>\n<\/td>\n

\n

-0.964**<\/sup><\/p>\n<\/td>\n

\n

-0.406<\/p>\n<\/td>\n

\n

-0.166<\/p>\n<\/td>\n

\n

1<\/p>\n<\/td>\n<\/tr>\n

\n

Sig. (2-tailed)<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n

\n

0.075<\/p>\n<\/td>\n

\n

0.484<\/p>\n<\/td>\n<\/tr>\n

\n

** Correlation is significant at the 0.01 level (2-tailed).<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

MCA PI: Middle cerebral artery pulsatility index<\/p>\n

EFW: Estimated fetal weight<\/p>\n

UA PI: Umbilical artery pulsatility index<\/p>\n\n\n

Table 2: Gestational age, anthropometric data and placental growth factor level (PlGF) in the studied neonates<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n<\/td>\n\n

Range<\/strong><\/p>\n<\/td>\n

\n

Mean<\/strong><\/p>\n<\/td>\n

\n

SD<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Gestational Age (GA) (weeks)<\/p>\n<\/td>\n

\n

37 – 39<\/p>\n<\/td>\n

\n

38.80<\/p>\n<\/td>\n

\n

2.00<\/p>\n<\/td>\n<\/tr>\n

\n

Neonatal Weight (Kg)<\/p>\n<\/td>\n

\n

2.40 – 3.50<\/p>\n<\/td>\n

\n

2.8972<\/p>\n<\/td>\n

\n

0.43900<\/p>\n<\/td>\n<\/tr>\n

\n

Neonatal Length (cm)<\/p>\n<\/td>\n

\n

47.0 – 53.0<\/p>\n<\/td>\n

\n

49.780<\/p>\n<\/td>\n

\n

1.3559<\/p>\n<\/td>\n<\/tr>\n

\n

W\/L (Kg\/cm)<\/p>\n<\/td>\n

\n

0.0 – 0.1<\/p>\n<\/td>\n

\n

0.084<\/p>\n<\/td>\n

\n

0.0370<\/p>\n<\/td>\n<\/tr>\n

\n

Neonatal Mid Arm Circumference (MAC) (cm)<\/p>\n<\/td>\n

\n

6.5 – 11.0<\/p>\n<\/td>\n

\n

8.988<\/p>\n<\/td>\n

\n

1.1726<\/p>\n<\/td>\n<\/tr>\n

\n

Neonatal Head Circumference (cm)<\/p>\n<\/td>\n

\n

30.0 – 36.0<\/p>\n<\/td>\n

\n

32.600<\/p>\n<\/td>\n

\n

1.5518<\/p>\n<\/td>\n<\/tr>\n

\n

Weight Z Score (Kg)<\/p>\n<\/td>\n

\n

(- 8.04) \u2013 (- 4.88)<\/p>\n<\/td>\n

\n

-6.9864<\/p>\n<\/td>\n

\n

0.96699<\/p>\n<\/td>\n<\/tr>\n

\n

Length Z Score (cm)<\/p>\n<\/td>\n

\n

(-1.78) – 1.87<\/p>\n<\/td>\n

\n

-0.0304<\/p>\n<\/td>\n

\n

0.87401<\/p>\n<\/td>\n<\/tr>\n

\n

W\/L Z Score (Kg\/cm)<\/p>\n<\/td>\n

\n

(-9.99) \u2013 (- 6.23)<\/p>\n<\/td>\n

\n

-8.7848<\/p>\n<\/td>\n

\n

1.15131<\/p>\n<\/td>\n<\/tr>\n

\n

Head circumference Z Score (cm)<\/p>\n<\/td>\n

\n

(-2.79) – 0.54<\/p>\n<\/td>\n

\n

-1.0352<\/p>\n<\/td>\n

\n

0.90455<\/p>\n<\/td>\n<\/tr>\n

\n

PlGF (pg\/ml)<\/p>\n<\/td>\n

\n

102.33 – 173.33<\/p>\n<\/td>\n

\n

142.6660<\/p>\n<\/td>\n

\n

17.92704<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
\"\"<\/td>\n\n

Table 3: Correlation between all the studied neonatal anthropometric parameters, gestational age and PlGF level in cord blood.<\/strong><\/p>\n

<\/p>\n

Click here to view Table<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Table 4: Linear regression analysis for cord blood PlGF level with UA PI and neonatal weight<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n\n
\n

Model<\/p>\n<\/td>\n

\n

Unstandardized Coefficients<\/p>\n<\/td>\n

\n

Standardized Coefficients<\/p>\n<\/td>\n

\n

T<\/p>\n<\/td>\n

\n

Sig.<\/p>\n<\/td>\n<\/tr>\n

\n

B<\/p>\n<\/td>\n

\n

Std. Error<\/p>\n<\/td>\n

\n

Beta<\/p>\n<\/td>\n<\/tr>\n

\n

1<\/p>\n<\/td>\n

\n

(Constant)<\/p>\n<\/td>\n

\n

196.293<\/p>\n<\/td>\n

\n

4.955<\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

39.614<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

UA PI<\/p>\n<\/td>\n

\n

-45.535<\/p>\n<\/td>\n

\n

4.129<\/p>\n<\/td>\n

\n

-0.933<\/p>\n<\/td>\n

\n

-11.029<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

2<\/p>\n<\/td>\n

\n

(Constant)<\/p>\n<\/td>\n

\n

30.087<\/p>\n<\/td>\n

\n

7.645<\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

3.935<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Neonatal weight<\/p>\n<\/td>\n

\n

38.428<\/p>\n<\/td>\n

\n

2.563<\/p>\n<\/td>\n

\n

0.962<\/p>\n<\/td>\n

\n

14.995<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

UA PI: Umbilical artery pulsatility index<\/p>\n

Dependent Variable: PlGF<\/p>\n\n\n

Discussion<\/strong><\/p>\n\n\n\n

Fetal growth\nis commonly modulated by the function of placenta, with the placenta serving\nthe fundamental respiratory, hepatic and renal functions of the fetus. The early\nproblems of the placenta can occur du to incomplete trophoblast invasion leading\nto a remodeling failure of the myometrial arteries and uteroplacental blood\nflow reduction that is generally correlated with pre-eclampsia and fetal growth\nrestriction19<\/sup><\/p>\n\n\n\n

Placental\ngrowth factor (PlGF) is a glycoprotein consisting of two subunits and belongs\nto the vascular endothelial growth factor (VEGF) family. It has been shown that\nPlGF has powerful proangiogenic impacts that lead to early placental vascular\ndevelopment 20<\/sup>. PlGF has a 53% homology to VEGF 21<\/sup> and it\nis a pleiotropic growth factor (angiokine) capable of stimulating blood vessel\nformation and stabilization of many tissues 22<\/sup>.<\/p>\n\n\n\n

The focus of\nour interest in the current research was to establish the interrelation between\nfetal PlGF, fetal Doppler parameters and neonatal growth parameters. The\nassessment of growth parameters at birth aids to predict the subsequent growth\nand development and risk of diseases. It has been demonstrated that the genetic,\nnutritional and the intrauterine conditions affect the fetal growth. Indeed growth\nparameters and gestational age assist in identifying the risk of neonatal\npathology. <\/p>\n\n\n\n

In our\nstudy, the abnormal fetal circulation was estimated by assessment of the latest\nDoppler ultrasound findings before delivery. Fetal blood flow was investigated\nin the umbilical and in the middle cerebral arteries and was correlated to PlGF\nlevel. Our findings indicated that regarding UAPI, there is a significant\nnegative correlation between PlGF and neonatal weight. However, insignificant\nnegative correlation was recorded between UAPI with MCAPI and estimated fetal\nweight (EFW). Gomez-Roig etal.23<\/sup> stated that in the third\ntrimester, UA Doppler PI and PlGF estimations aid for identifying the\npregnancies at the great risk of negative perinatal outcomes owing to intrauterine\ngrowth restriction (IUGR). They concluded that, even though testing of joint\ndoesn\u2019t provide any no predictive advantage over UA Doppler PI alone, both\ndiagnostic methods can be used interchangeably for this objective. Similarly,\nMolvarec et al. 24<\/sup>found slight or very slight level of PlGF in\nnormal blood flow fetuses and in the neonates with IUGR and the PlGF is negatively\ncorrelated with PI values in the umbilical and uterine arteries as well. The\ncorrelation between serum levels of the angiogenic growth factor in the fetus\nand Doppler ultrasound measurements of the uterine and umbilical arteries in\nIUGR mirrors the fetal disorders severeness. The incorporation of both parameters\ncan be helpful in the monitoring for early prognosis of pregnancy complications\nin the future25<\/sup>.<\/strong> Also, in agreement with our results, Taylor\net al. 26<\/sup>reported that, in women with normal blood pressure\nand with IUGR, PlGF levels are reduced versus normal controls. Thus, PlGF may\nprovide useful information to recognize fetuses demanding immediate delivery,\nand those at stake of subsequent unfavorable consequences not distinguished by\nfetal flow Doppler ultrasonography. <\/p>\n\n\n\n

The data in\nthe present research indicated significant positive correlation between\numbilical cord blood PlGF and GA. Interestingly, the levels of fetal PlGF have\nbeen found to be correlated with fetal growth; reduced values of fetal PlGF\nwere accompanied by delivery of SGA neonates 6<\/sup>. Fetuses with SGA represent\na heterogeneous category comprising fetuses who are less developed than normal\nand those with fetal growth restriction (FGR) leading to a low birth weight 27<\/sup>.<\/strong>\nDifferences of umbilical cord blood PlGF levels have been observed between neonates\nwith SGA and AGA 28<\/sup>. <\/strong>This is in accordance to the findings of\nthe present investigation.<\/p>\n\n\n\n

The\nanthropometric parameters of the new-born population are considered as a significant\nscientific research tools to study the determinants and consequences of weakened\nor exaggerated fetal growth 29<\/sup>.<\/strong> Our results showed significant\ncorrelation between the gestational age and all anthropometric measures. In accordance\nwith our findings, Thawani et al. 30<\/sup> mentioned that\ngestational age has an excellent linear correlation with birth weight, crown\nheel-length, mid-upper arm-circumference, and head circumference. <\/p>\n\n\n\n

The most fundamental\nfactor for growth, and development of newborns is the gestational age (GA),\nbecause newborns morbidity and mortality are mainly related to GA as well as anthropometric\nparameters like length, birth weight (BW), head, arm, and chest circumferences 31<\/sup>.<\/strong>\nRecently, a positive correlation between GA and anthropometric variables has\nbeen demonstrated within newborns. From anthropometric measurements, BW was the\nmost commonly used anthropometric indicator of birth size 32<\/sup>.<\/strong> Birth weight\n(BW) is a crude summary of fetal growth, and the similar birth weight may be\nthe consequence of many different paths of growth 33<\/sup>.<\/strong> Mid arm\ncircumference (MAC) was also correlated well with GA; it is\nconsidered as a good individual anthropometric parameter for GA assessment in\nneonates 34<\/sup>.<\/strong> Also, neonatal MAC within 72 h of birth is a good\nrepresentative for BW in the developing nations and it is accounted as easy,\nconvenient and significant anthropometrical parameter in detection of low birth\nweight newborn babies 35<\/sup>.<\/strong> <\/strong>Measuring the neonatal foot length, chest circumference and MAC have\nbeen found to be reasonable tools for estimating low BW (< 2500 g) and\nprematurity (gestational age < 37 weeks) 36<\/sup>.<\/strong> Paulsen et\nal.37<\/sup>observed that foot length, chest circumference and MAC all\ncorrelated well with BW and GA and had reasonable sensitivity and specificity\nfor the detection of SGA. Moreover, a positive correlation has been\ndetected between foot length as well as arm\/head and chest circumferences\nand GA, BW in addition to body length 38<\/sup>.<\/strong> Gandhi et al.39<\/sup>\nconducted a study in a Western Indian population about using head circumference\nas a primitive tool for estimation of GA in neonates and they found a strong\ncorrelation between GA and head circumference.<\/p>\n\n\n\n

Placental\ngrowth factor(PlGF) is generated by trophoblasts which promote\nproliferation, migration and activation of endothelial cells 10<\/sup>.<\/strong> <\/strong>PlGF has been known to cross placenta, thus PlGF of fetal and maternal\nor placental origin is existed in the umbilical cord blood. However, minute\ncorrelations were observed between the level of PlGF in the umbilical cord\nblood on one side and maternal levels of PlGF and weight of placenta on the\nother. This indicates the predominance of fetal origin of PlGF in the umbilical\ncord blood 28<\/sup>.<\/strong><\/p>\n\n\n\n

The current\nfindings showed significant positive correlation between cord blood PlGF and\nthe all anthropometric parameters of the neonates implicated in the present\nstudy. The interrelation between PlGF of fetal origin and the clinical outcome\nfetal growth restriction (FGR) has been reported 40<\/sup>. Broere-Brown et al. 28<\/sup> demonstrated that fetal PlGF is correlated with the\ngrowth of the fetus, with steady findings for BW, manner of growth, and the\nclinical outcome FGR. These investigators reported that there is an interrelation\nbetween fetal PlGF levels and fetal growth measures. Correlative\nstudies have demonstrated that the elevated maternal soluble Flt1 (sFlt1), PlGF\nreceptor, and the reduced PlGF, along with the decreased umbilical cord blood PlGF,\nare linked with low BW 6<\/sup>. <\/strong>These findings confirmed those of\nBroere-Brown et al. who established that the lower PlGF levels in the cord\nblood were linked with a lower BW 28<\/sup>Regarding the systemic impacts\nof sFlt-1 on fetal growth and development, it has been found that increased sFlt-1 umbilical\nlevels are inversely correlated with fetal growth in normal pregnancies 6<\/sup>and sFlt-1 levels are also inversely associated with body weight percentile\nin preterm infants 41<\/sup>.<\/strong> It is well known that the\nbioavailability of PlGF is reduced by binding to its receptor sFLT-1 42<\/sup>.<\/strong>\nGarcia-Manau et al. concerned with the ratio of  sFlt-1\/PlGF in the detection of FGR, exploring\nthat median values sFlt-1\/PlGF enhanced alongside the FGR severity and confirmed\nan inverse association between the values of sFlt-1\/PlGF ratio and GA at the\nmoment of delivery43<\/sup>.<\/p>\n\n\n\n

It has been\nstated that low PlGF MoM quintiles are also related to FGR. Thus, fetal PlGF\nmight be an optimistic biochemical marker to estimate the growth of the fetus\nand FGR aberrations retrospectively, allowing follow-up of these neonates 28<\/sup>FGR is usually proved by a low BW and a high probability for boring neonate\nwith SGA 44<\/sup>. <\/strong>Thus, the clinical outcome FGR is frequently recognized\nas SGA 45<\/sup>.   <\/strong><\/p>\n\n\n\n

Neonates who have FGR may represent\na susceptible category with a high chance of less efficient hearts in childhood\n46<\/sup>. Thus, low levels\nof PlGF in the cord blood could be an important indication of this high risk. Anyhow,\nit must account the probability that fetuses with small weight deliver little\nPlGF. In that situation the behind machinery of the fetuses being small induce\nthe probable counteractive consequences in the future life accompanied with FGR\nrather than PlGF itself. Fetuses with FGR are frequently delivered with a\nnormal BW, but still represent a susceptible class with a high risk for\ncardiovascular diseases in childhood. The epidemiologic\nstudies have proposed a correlation between low BW and\/or FGR and elevated rate\nof cardiovascular mortality in future life. Moreover, experimental and clinical\nresearches have evidenced that persistent nutrient and oxygen deficiency that\nare coupled with FGR stimulate adaptive cardiovascular alterations that might elucidate\nthis association. FGR led to metabolic programming that may enhance metabolic\nsyndrome risk and in turn cardiovascular morbidity in the adult life. Furthermore,\nFGR is highly connected with fetal cardiac and arterial remodeling and a\nsubclinical <\/p>\n\n\n\n

situation of\ncardiovascular dysfunction47<\/sup>. Recognition of this susceptible subjects\nby the follow-up of P1GF in the postnatal period, allows prohibiting the prospective\ndeleterious outcomes in later life 28<\/sup>.<\/strong> PlGF could be\nconsidered a promising tool for identifying the neonates at risk for adverse consequences\n48<\/sup>.<\/strong><\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

The data in\nthe present approach shed light on the impact of fetal placental growth factor (PGF)\nlevel, which may not represent maternal level of placental growth factor, on\nthe neonatal adverse growth pattern. In addition, fetal placental growth factor\nwith fetal Doppler parameters may be considered a promising predictive\nbiomarker for identifying those neonates at risk for detrimental childhood\noutcomes. <\/p>\n\n\n\n

Acknowledgements<\/strong><\/p>\n\n\n\n

Not applicable.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

The authors declare that\nthey have no competing interests.<\/p>\n\n\n\n

Funding Source<\/strong><\/p>\n\n\n\n

This\nresearch received no specific grant from any funding agency in the public,\ncommercial, or not-for-profit sectors.<\/p>\n\n\n\n

Authors’ contributions<\/strong><\/p>\n\n\n\n

E.R.A. suggested the idea\nof the manuscript, A.H.K. performed the anthropometric measurements of the\nneonates, L.S.S. performed the statistical analysis, H.H.A. conducted the\nbiochemical analysis of PlGF and wrote the manuscript, M.T.S. carried out the\nclinical examination of the neonates, S.S. carried out the clinical examination\nof the pregnant women at delivery time and collected the blood samples from the\numbilical cord, M.A.G. participated in writing the manuscript,  All authors reviewed the manuscript.<\/p>\n\n\n\n

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