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Keywords:

  • early onset intrauterine growth restriction;
  • early onset preeclampsia;
  • early second trimester;
  • logistic regression analysis;
  • serum placental growth factor

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

Aim

To determine whether maternal serum placental growth factor (PlGF) estimation in early second trimester (20–22 weeks of gestation) can predict the occurrence of early onset preeclampsia and/or early onset intrauterine growth restriction (IUGR).

Material and Methods

A prospective cohort study was conducted on 722 women with singleton pregnancies, screened from the antenatal clinic, and serum PlGF levels were estimated at 20–22 weeks of gestation. A cut-off value of <155 pg/mL for serum PlGF was determined by receiver operating characteristic (ROC) curve analysis for identifying pregnant women at risk of developing early onset preeclampsia and/or early onset IUGR. Preeclampsia and IUGR were classified as early onset when diagnosed by 32 weeks of gestation. Univariate logistic regression analysis was used to analyze the association between serum PlGF level <155 pg/mL and the two outcome measures (i.e. early onset preeclampsia and early onset IUGR) and odds ratio (OR) was computed. P-value < 0.05 was considered statistically significant.

Results

Maternal serum PlGF level <155 pg/mL at 20–22 weeks of gestation had a strong association with early onset preeclampsia (OR 8.35; 95% CI 1.79–18.94; P = 0.007) and with early onset IUGR (OR 10.73; 95% CI 4.08–20.23; P = 0.000). The sensitivity of serum PlGF < 155 pg/mL for predicting early onset preeclampsia and early onset IUGR were 82 and 84, respectively.

Conclusion

Maternal serum PlGF level estimation in early second trimester (20–22 weeks of gestation) may be useful in predicting the occurrence of early onset preeclampsia and/or early onset IUGR.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

Preeclampsia and intrauterine growth restriction (IUGR) are known major factors in perinatal morbidity and mortality.[1] Prediction of preeclampsia and/or IUGR has been a major research issue for the last two decades.[2] Researchers have now accepted that early onset and late onset preeclampsia are the two different forms of the disease.[3] Early onset preeclampsia is characterized by utero-placental insufficiency and is commonly associated with IUGR, whereas late onset preeclampsia is mostly associated with mild maternal disease and low incidence of fetal involvement with favorable perinatal outcome.[3, 4] Hence it may be opined that detection of pregnant women at an increased risk of developing early onset preeclampsia and/or early onset IUGR followed up by careful monitoring and appropriate intervention could have significant impact on the perinatal outcome.

The current etiological concept for both preeclampsia and IUGR implies an imbalance of angiogenic growth factors. The activity of these factors requires to be carefully orchestrated in the developing placenta to establish a suitable vascular network for supply of oxygen and nutrients to the fetus.[5] Mammalian placenta thus requires extensive angiogenesis, which is chiefly regulated by the vasculo-endothelial growth factor (VEGF) family.[6, 7] Placental growth factor (PlGF) is a polypeptide growth factor and is a member of the VEGF family,[8] which regulates the development of the placental villi during early gestation. This regulatory effect is essential for establishing placental blood circulation to ensure a normal pregnancy outcome.[9] The expected trend of PlGF concentration in normal pregnancy is a steady increase during first two trimesters, a peak at 29–32 weeks and a consistent decline thereafter.[10, 11] In preeclampsia and in IUGR maternal blood levels of serum fms like tyrosine kinase (sFlt-1) are upregulated.[10, 12] Concentrations of sFlt-1 are higher in women with early onset forms of the disease.[12, 13] The presence of excess sFlt-1 in the circulation of women with preeclampsia as well as in isolated IUGR lead to functional deficiency of serum PlGF levels.[3, 14] Differences in the levels of serum PlGF with respect to normal pregnancies are considerably more pronounced in early onset forms of the disease.[3]

The aim of the present study was to determine whether maternal serum PlGF level estimation in early second trimester (20–22 weeks of gestation) of pregnancy can predict the occurrence of early onset preeclampsia and/or early onset IUGR.

Material and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

During a 15-month period between January 2011 and March 2012 a prospective cohort study was conducted in the Department of Anatomy, Lady Hardinge Medical College, New Delhi, India, in association with the Department of Obstetrics and Gynecology and the Department of Radiology of the same institution. A total of 722 pregnant women with singleton pregnancies, between 20–22 weeks of gestation, were screened from the antenatal clinic of associated Smt. Sucheta Kriplani Hospital, to participate in the study. The first trimester ultrasound report was the basis for determining the gestational age and excluding any case of congenital abnormality. The study was approved by the hospital ethics committee (letter no. F12/7434/2010/LHMC/Ethics/102) and written consent from each woman included in the study population was obtained. The demographic and clinical characteristics of the study population have been documented in Table 1. Socioeconomic status of study population was determined according to the revised Kuppuswamy's socioeconomic status scale.[15]

Table 1. Demographic and clinical characteristics of the study population
CharacteristicNo early onset preeclampsia/early onset IUGR (n = 678)Early onset preeclampsia + early onset IUGR (n = 11)Early onset IUGR (n = 21)P-value*
  1. From the study population, 12 pregnant women developed miscarriage/preterm delivery (placental abruption/spontaneous preterm labor/premature rupture of membrane) and have not been included in this table. No newborn was reported with any congenital abnormality from the study population of pregnant women.

  2. *The statistical significance of the difference in the values between pregnant women with no early onset preeclampsia (EOPE)/early onset IUGR (EOIUGR) and those with EOPE + EOIUGR is expressed as p1; between those with no EOPE/EOIUGR and those with EOIUGR as p2; between those with EOPE + EOIUGR and those with EOIUGR as p3. The values represented in bold are statistically significant.

  3. †For this study the authors used the revised Kuppuswamy's socioeconomic status scale to determine the socioeconomic status of the study population. According to this scale there are five socioeconomic classes: upper; upper middle; lower middle; upper lower; lower; ‡Ethnicity of the study population was determined on the basis of domicile records; §Mean birth weight of the newborn in pregnant women with neither early onset preeclampsia nor early onset IUGR was relatively low and this could be due to the fact that majority of the pregnant women in this group belonged to lower middle/upper lower/lower socioeconomic class thereby subjected to poor nutritional intake.

  4. IUGR, intrauterine growth restriction; NA, not applicable; SD, standard deviation.

Maternal age at enrollment for study (years; mean ± SD)25.44 ± 3.1822.73 ± 2.0123.52 ± 2.75

p1- 0.009

p2- 0.042

p3- 0.07

Socioeconomic status

Upper middle – 14

Lower middle – 184

Upper lower – 266

Lower – 214

Lower middle – 2

Upper lower – 6

Lower – 3

Lower middle – 11

Upper lower – 5

Lower – 5

Body mass index (mean ± SD)23.56 ± 0.9522.14 ± 0.7922.82 ± 0.89

p1- 0.033

p2- 0.062

p3- 0.092

Nulliparous (%)374 (55%)9 (82%)17 (81%)
Ethnicity (%)

Indo-Aryan (74%)

Dravidian (22%)

Mongoloid (4%)

Indo-Aryan (86%)

Dravidian (14%)

Indo-Aryan (82%)

Dravidian (17%)

Mongoloid (1%)

History of smoking14NilNil
History of chronic hypertension2NilNil
History of autoimmune disease2NilNil
Consanguineous marriage51Nil
Gestational age at onset of preeclampsia (early onset) (weeks; range)NA29–31NA
Gestational age at delivery (weeks; mean ± SD)38.74 ± 2.3833.82 ± 0.6734.86 ± 0.79

p1- 0.007

p2- 0.019

p3- 0.12

Birth weight of newborn (kg; mean ± SD)2.45 ± 0.32§1.52 ± 0.091.61 ± 0.13

p1- 0.016

p2- 0.029

p3- 0.24

Serum PlGF estimation was done in all the 722 pregnant women enrolled in the study, at 20–22 weeks of gestation in the Department of Anatomy. Maternal venous blood samples were collected in EDTA vials from the medial cubital vein. All blood samples were centrifuged immediately after collection at 3000 rpm for 15 min and serum was aliquotted and stored at −80°C. Estimation of free PlGF levels were done by enzyme linked immunosorbent assay (ELISA) technique using the DRG PlGF Enzyme Immunoassay Kit (Marburg, Germany). All samples were measured in duplicate after being appropriately diluted such that the readings fitted within the standard curve. In this study the intra-assay co-efficient of variability (CV) was <5% and the inter-assay co-efficient of variability (CV) was <10%. These results substantiate the repeatability/precision of the immunoassay test results.

Following the estimation of serum PlGF, all the 722 pregnant women under study were admitted in the antenatal wards and the clinicians assigned to monitor them were blinded to the results of serum PlGF estimation. During their stay in the hospital 12 women developed either placental abruption/spontaneous preterm labor/premature rupture of membrane leading to miscarriage/preterm delivery, and they were subsequently transferred to the postnatal wards for observation. The remaining 710 pregnant women in this study underwent an ultrasound examination and pulse wave Doppler velocimetry of the umbilical artery at the onset of the 32nd week of gestation for diagnosis of IUGR. This procedure was performed in the Department of Radiology with Philips HD7 Ultrasound System (Manufactured in Shanghai, Peoples Republic of China), by a team of three experienced sonographers. The end-diastolic blood flow velocity in the umbilical artery was documented and umbilical artery pulsatility index (PI) was recorded in each case. In this study, both preeclampsia and IUGR were classified as early onset when the diagnosis was made by the onset of 32 weeks of gestation and this cut-off was chosen in accordance with the study by Crispi et al.[16] Preeclampsia was diagnosed in the study women according to the definition laid down by the International Society for the Study of Hypertension in Pregnancy.[17] IUGR was diagnosed sonographically, when the abdominal circumference and the estimated fetal weight was <10th centile in accordance with the formula by Hadlock et al.[18] and the Doppler PI in the umbilical artery >95th percentile for the 32nd week of gestation. Pathological umbilical artery pulsatility indices were included in the definition of early onset IUGR to ensure the inclusion of only those fetuses in which IUGR was caused by placental insufficiency.

The authors had conducted a similar study on 294 pregnant women (186 nulliparous) with singleton pregnancies, selected from the antenatal wards, before undertaking this study and serum PlGF estimation was done at 20–22 weeks, using the same procedure that would be used in the main study. Four pregnant women were diagnosed with both early onset preeclampsia and early onset IUGR and seven women were diagnosed with isolated early onset IUGR according to the same criteria that has been laid down by the authors in the main study. The distribution of serum PlGF levels in pregnant women (n = 294) from this study is shown in Table 2. With the help of these data, a cut-off value of <155 pg/mL for serum PlGF was determined by receiver operating characteristic (ROC) curve analysis, for identifying pregnant women at risk of developing early onset preeclampsia and/or early onset IUGR (Fig. 1).

figure

Figure 1. Receiver operating characteristic (ROC) curve to determine the cut-off value of serum PlGF level for identifying pregnant women at risk of developing early onset preeclampsia and/or early onset IUGR. Area under the curve (AUC) – 0.982; 95% confidence interval: 0.960–0.994; standard error 0.007; P < 0.000. PlGF, placental growth factor; IUGR, intrauterine growth restriction.

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Table 2. Distribution of serum PlGF levels in pregnant women for determining its cut-off value for predicting early onset preeclampsia and/or early onset IUGR
Distribution of valuesLevels of serum PlGF recorded at 20–22 weeks of gestation (pg/mL)
No early onset preeclampsia/early onset IUGR (n = 283)Early onset preeclampsia + early onset IUGR (n = 4)Early onset IUGR (n = 7)
  1. The above table shows the PlGF values from the study conducted on 294 pregnant women, prior to the actual study, exclusively to determine the cut-off value of serum PlGF that would be used in the actual study. The serum PlGF values in all those women who developed early onset preeclampsia + early onset IUGR and those who developed only early onset IUGR were taken into consideration while determining the cut-off value. IUGR, intrauterine growth restriction; PlGF, placental growth factor.

Minimum12296102
Q1 (first quartile)188107
Median204117128
Q3 (third quartile)264142
Maximum416138155

Statistical analysis

Interobserver reliability of umbilical artery PI was assessed with the help of interclass correlation coefficient (ICC), which was measured by MedCalc version 11.6.1.0. Univariate Logistic Regression analysis was performed to analyze the association between serum PlGF < 155 pg/mL and the incidence of early onset preeclampsia and early onset IUGR. Software named Logistic Regression (by John. C. Pezulto, instructions modification by Kevin M. Sullivan) version 05.07.20 was used for the same. ROC curve analysis was performed using MedCalc version 11.6.1.0. Box and whisker plot was prepared with the help of Microsoft Office Excel 2003 version. Comparisons between groups were performed by Kruskal-Wallis test. P < 0.05 was considered statistically significant for this study.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

The study population consisted of 722 pregnant women with singleton pregnancies, who underwent serum PlGF estimation between 20 and 22 weeks of gestation. Among them, serum PlGF levels were <155 pg/mL in 258 pregnant women and in the remaining 464 women serum PlGF levels were >155 pg/mL. Among the 258 pregnant women who had serum PlGF levels <155 pg/mL, nine women (9/258; 3.5%) went on to develop early onset preeclampsia, whereas two women (2/464; 0.4%) developed early onset preeclampsia among the 464 women in whom serum PlGF levels were >155 pg/mL (Fig. 2).

figure

Figure 2. Flowchart showing a schematic representation of the main events of the study from onset to the development of the outcome measures in the study population. PlGF, placental growth factor; EOPE, early onset preeclampsia; EOIUGR, early onset intrauterine growth restriction.

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At the onset of the 32nd week of gestation the available study population was subjected to ultrasound examination and Doppler velocimetric analysis of the umbilical artery, for the diagnosis of early onset IUGR. Umbilical artery pulsatility index (PI) was calculated in each case and the ICC for umbilical artery PI in this study was 0.78 (95% CI, 0.64–0.88). Such good repeatability[19, 20] suggests that the Doppler parameter is reliable in a clinical setting. All the 11 pregnant women who had developed early onset preeclampsia were diagnosed as having early onset IUGR. Further 21 pregnant women from the study population who did not develop early onset preeclampsia, were detected with early onset IUGR in the fetuses. In other words, total of 32 pregnant women from the study population were diagnosed as having early onset IUGR at 32nd week of gestation. Twenty-seven women (27/258; 10.5%) with early onset IUGR had serum PlGF < 155 pg/mL at 20–22 weeks of gestation and the remaining five women (5/464; 1.1%) had serum PlGF > 155 pg/mL at the same gestational interval (Fig. 2).

Univariate logistic regression analysis revealed that maternal serum PlGF < 155 pg/mL at 20–22 weeks of gestation is an independent variable in the occurrence of both early onset preeclampsia (odds ratio 8.35; 95% CI, 1.79–18.94) as well as early onset IUGR (odds ratio 10.73; 95% CI, 4.08–20.23) in pregnant women and in both cases, the association was found to be statistically significant (Table 3).

Table 3. Univariate logistic regression analysis to determine the association of maternal serum PlGF level <155 pg/mL at 20–22 weeks of gestation with the occurrence of early onset preeclampsia and early onset IUGR
Primary outcome measuresVariable under study
Serum PlGF < 155 pg/mL at 20–22 weeks of gestation
Odds ratio95% confidence intervalP-valueSensitivity (%)Specificity (%)
LowHigh
  1. IUGR, intrauterine growth restriction; PlGF, placental growth factor.

Early onset preeclampsia8.351.7918.940.0078265
Early onset IUGR10.734.0820.230.0008467

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

In recent times a two-stage model is commonly accepted to explain the pathophysiological basis of preeclampsia and IUGR: shallow trophoblast invasion and reduced placental perfusion.[21] During normal pregnancy, the fetus must receive sufficient oxygen and nutrients via the maternal spiral arteries. To ensure this, the spiral arteries should undergo vascular remodeling, which requires extra villous trophoblast cells to invade the decidual part of the spiral arteries between 8–12 weeks of gestation. These trophoblast cells adopt an endothelial phenotype from an epithelial one, thereby reducing the resistance of the maternal spiral arteries.[22] In pregnancies complicated by preeclampsia, the vascular remodeling of the maternal spiral arteries is restricted to the superficial portion of the deciduas.[23] With the advancement of pregnancy as the failure to dilate becomes more pronounced in the spiral arteries, placentation, placental angiogenesis and placental perfusion are further reduced. In addition to an increased secretion of sFlt-1, which may bind free PlGF, uteroplacental ischemia might also down-regulate the PlGF protein expression and production.[5] These alterations in the placental vascular bed worsens the blood supply to the fetus resulting in reduced fetal weight, which could be shown by an increased resistance in the umbilical arteries measured by umbilical artery Doppler ultrasonography.[24] In early onset forms of preeclampsia and/or IUGR the changes in the fetoplacental circulation are more pronounced, adversely affecting the maternal and fetal health, resulting in the delivery of the fetus with severe prematurity and its associated complications.[16]

Recent evidence suggests that estimation of serum PlGF levels could be useful for early prediction of preeclampsia.[10] Chappel et al. reported that maternal serum PlGF estimation at 24 weeks of gestation contributed significantly to the prediction of preeclampsia.[25] Madazli et al. noted that mid-trimester maternal serum PlGF has the highest predictive value for early identification of preeclampsia.[26] Erez et al. observed that serum PlGF levels increase considerably between first and second trimester of pregnancy and in pregnant women at an increased risk of developing preeclampsia this increase in serum PlGF levels is subnormal.[27] Hence it may be suggested that in early second trimester there would be less overlapping of the serum PlGF levels between normotensive pregnant women and those at risk of developing preeclampsia. The authors of the present study had observed that maternal serum PlGF levels at 20–22 weeks of gestation had a strong association with the occurrence of preeclampsia;[28] however, most of the preeclampsia cases reported in that study were of late onset (developing after 32 weeks of gestation).

In the present study the authors noted that serum PlGF level <155 pg/mL at 20–22 weeks of gestation had a strong association with the occurrence of early onset preeclampsia (odds ratio 8.35; 95% CI, 1.79–18.94) and also with early onset IUGR (odds ratio 10.73; 95% CI, 4.08–20.23) (Table 3). Maternal serum PlGF level <155 pg/mL had a sensitivity of 82 and 84 for identifying pregnant women at risk of developing early onset preeclampsia and early onset IUGR respectively (Table 3), and these values are reasonably high, which is an essential standard for any screening test. Our observations are in accordance with those of Espinoza et al., who had also established a strong association between serum PlGF levels at 22–26 weeks of gestation with early onset preeclampsia.[29] The results of our study are also consistent with the findings of Crispi et al., where they had showed that serum PlGF levels at 24 weeks of gestation had a high positive predictive value in predicting the occurrence of early onset preeclampsia/IUGR.[16] However, they had acknowledged that a small sample size (n = 114) limited the interpretations of the results of their study. In contrast to the above observations, Savvidou et al. had estimated maternal serum concentrations of sFlt-1 at 23–25 weeks of gestation and reported that the increase in sFlt-1 level was not evident in pregnancies with impaired placentation that subsequently developed preeclampsia/IUGR.[30]

Preeclampsia is characterized by utero-placental insufficiency that results in up-regulation of maternal serum levels of sFlt-1.[12] Increased sFlt-1 during preeclampsia is associated with decreased free PlGF levels in maternal blood,[14] which leads to defective angiogenesis and widespread endothelial injury.[10] These changes taking place in the placental vascular bed are actually responsible for the clinical features of preeclampsia and nutritional deficiency to the fetus.[13] Hence it may be suggested that a low maternal serum PlGF level highlights the existence of a deficit in placental angiogenesis and depicts the actual systemic endothelial damage in the placental vascular tree (characteristic of preeclampsia and IUGR) and this could be the possible explanation of the strong association between serum PlGF levels and the occurrence of early onset preeclampsia and early onset IUGR, as observed in the present study.

Although early onset preeclampsia and IUGR are often considered together as consequences of placental insufficiency (characterized by low maternal serum PlGF levels), in the present study the authors noted that of the 32 pregnant women who went on to develop early onset preeclampsia and/or early onset IUGR, only 11 women (11/32; 34%) developed both the conditions, whereas the remaining 21 women (21/32; 66%) did not develop preeclampsia but were detected with IUGR at the onset of the 32nd week of gestation (Fig. 2). The median and interquartile range (IQR) of serum PlGF levels in women with neither early onset preeclampsia nor early onset IUGR; with early onset preeclampsia + early onset IUGR; and those with isolated early onset IUGR have been documented in Table 4 Figure 3. The authors would like to mention at this point that there were no significant difference in median (IQR) serum PlGF level between women with early onset preeclampsia + early onset IUGR and those with isolated early onset IUGR (P = 0.8). In other words, utero-placental insufficiency was almost at the same level at 20–22 weeks of gestation in both the groups; however, the eventual outcome was different. Such disparate results could be explained by the fact that the placental oxidative stress in terms of increased generation of reactive oxygen species (ROS) is greater in cases with both preeclampsia and IUGR as compared to those with IUGR alone.[31, 32] Subsequently the maternal circulation to the placenta is compromised to a greater degree in cases of early onset preeclampsia associated with growth restriction in fetuses than in IUGR alone.[33] However, Burton et al. had opined that there are many common features in the placental changes seen in preeclampsia + IUGR and isolated IUGR and that the differences are mostly a matter of degree. They had suggested that the two conditions represent different points along a spectrum of placental pathologies secondary to deficient spiral artery conversion.[34] The above discussion justifies the ultrasound examination and Doppler velocimetry of the umbilical artery at the onset of the 32nd week of gestation for all the pregnant women with serum PlGF levels <155 pg/mL at 20–22 weeks of gestation, for confirming the diagnosis of IUGR in pregnant women who developed preeclampsia by 32 weeks of gestation, but more significantly to detect the cases with isolated IUGR from the population which did not develop early onset preeclampsia.

figure

Figure 3. Box and whisker plot showing the distribution of serum PlGF values in different subgroups of the study population. Boxes show median and interquartile range (IQR) and whiskers represent the extremes of distribution. The symbols representing different values are shown at the right side of the figure. PlGF, placental growth factor; EOPE, early onset preeclampsia; EOIUGR, early onset intrauterine growth restriction.

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Table 4. Distribution of serum PlGF levels in the different subgroups of the study population
Distribution of valuesLevels of serum PlGF recorded at 20–22 weeks of gestation (pg/mL)
No early onset preeclampsia/early onset IUGR (n = 678)Early onset preeclampsia + early onset IUGR (n = 11)Early onset IUGR (n = 21)
  1. From the study population, 12 pregnant women developed miscarriage/preterm delivery (placental abruption/spontaneous preterm labor/premature rupture of membrane). Serum PlGF levels recorded in these women have not been included in this table. IUGR, intrauterine growth restriction; PlGF, placental growth factor.

Minimum1128892
Q1 (first quartile)146120128
Median210134140
Q3 (third quartile)364150152
Maximum445205225

The authors observed that among those pregnant women who developed early onset preeclampsia + early onset IUGR (n = 11), the difference in the median serum PlGF levels (recorded at 20–22 weeks of gestation) for different gestational weeks of the onset of preeclampsia was statistically significant (P < 0.05). It was noted that lower the serum PlGF level was at 20–22 weeks of gestation, earlier was the onset of preeclampsia or in other words severer the disease was in these pregnant women (Table 5 & Fig. 4). Based on the above observation, the authors may comment that serum PlGF levels in pregnant women at 20–22 weeks of gestation could be correlated with the severity of preeclampsia.

figure

Figure 4. Box and whisker plot showing the distribution of serum PlGF values in pregnant women with early onset preeclampsia and early onset IUGR (EOPE + EOIUGR) according to the different gestational weeks for the onset of preeclampsia. Boxes show median and interquartile range (IQR) and whiskers represents the extremes of distribution. The symbols representing different values are shown at the right side of the figure. For the serum PlGF values at 30 and 31 gestational weeks, boxes were not formed as there were no first quartile (Q1) and third quartile (Q3) values. PlGF, placental growth factor; IUGR, intrauterine growth restriction.

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Table 5. Distribution of serum PlGF levels in pregnant women with early onset preeclampsia and early onset IUGR (EOPE + EOIUGR) according to the different gestational weeks for the onset of preeclampsia
Distribution of valuesLevels of serum PlGF recorded at 20–22 weeks of gestation in pregnant women who developed EOPE + EOIUGR (pg/mL) (n = 11)
Onset of preeclampsia at 29 weeks (n = 5)Onset of preeclampsia at 30 weeks (n = 3)Onset of preeclampsia at 31 weeks (n = 3)
  1. IUGR, intrauterine growth restriction; PlGF, placental growth factor.

Minimum88134150
Q1 (first quartile)110
Median120144188
Q3 (third quartile)124
Maximum128148205

Early prediction of pregnant women at risk of developing early onset preeclampsia and/or early onset IUGR is crucial for the effectiveness of prophylactic interventions.[21] Among various possible prophylactic interventions, low dose aspirin has been reported to be useful in reducing the risk of preeclampsia by reducing the resistance to the blood flow in the uterine artery,[35] which could lead to better placentation process and higher birth weight of the new born.[36, 37] The current goal in obstetrical management of complicated pregnancies is to allow the fetus to mature within a potentially hostile, intrauterine environment, while assuring safety of both the mother and the fetus.[5] Hence the authors would suggest that all the pregnant women identified as having utero-placental insufficiency (serum PlGF < 155 pg/mL) at 20–22 weeks of gestation should be monitored intensively, diagnosed cases of early onset preeclampsia could be managed as per standard protocol and once IUGR is detected at the onset of 32nd week of gestation, the affected fetuses could be subjected to serial biophysical profile evaluation or cardiotocography[38] and the timing for the delivery of the growth restricted fetus could be determined accordingly.

After analyzing the findings of the present study the authors came to the conclusion that maternal serum PlGF estimation in early second trimester (20–22 weeks) of pregnancy may be useful in predicting the occurrence of early onset preeclampsia and/or early onset IUGR. However, the authors would like to emphasize that the results of this study and the conclusions drawn thereof are to be interpreted cautiously, as this study has the inherent limitation of being a single center study. Nevertheless, it has the advantage of evaluating a homogenous low risk population involving a selected few investigators and a single machine for serum PlGF estimation. In the present study the cost of screening each pregnant women for serum PlGF level was Rs.500/- (US$10 US approx.) and the cost of diagnosing IUGR at 32nd week of gestation was Rs. 1200/- (US$US approx.). But we believe that with large scale usage the cost of the overall procedure could be brought down further.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

The authors are thankful to all the senior consultants of the Department of Obstetrics and Gynecology and the Department of Radiology, Lady Hardinge Medical College and Smt. Sucheta Kriplani Hospital, New Delhi, India, for their support and co-operation.

The authors are grateful to the authorities of Lady Hardinge Medical College for funding the entire project.

Disclosure

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References

The authors hereby declare that they have no conflict of interest whatsoever (financial, personal, political, intellectual or religious). We, to the best of our knowledge, hereby declare that we have nothing to disclose in this regard.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Material and Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Disclosure
  9. References
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