Archive
Search

You can search published articles.

Journal Information

Online ISSN
1305-3124

Established
1993

Editors-in-Chief
​Cihat Şen, ​Nicola Volpe

Editors
Daniel Rolnik, Mar Gil, Murat Yayla, Oluş Api

Statistics Editor
Resul Arısoy

Fetal gender-specific difference for placental volume assessed with 3D-ultrasonography

Burcu Artunç Ülkümen, Halil Gürsoy Pala, Yıldız Uyar, Faik Mümtaz Koyuncu, Yeşim Bülbül

Article info

Fetal gender-specific difference for placental volume assessed with 3D-ultrasonography. Perinatal Journal 2016;24(3):156-161 DOI: 10.2399/prn.16.0243008

Author(s) Information

Burcu Artunç Ülkümen1,
Halil Gürsoy Pala2,
Yıldız Uyar1,
Faik Mümtaz Koyuncu1,
Yeşim Bülbül1

  1. Celal Bayar Üniversitesi Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, Manisa
  2. Sağlık Bilimleri Üniversitesi Tepecik Eğitim ve Araştırma Hastanesi, Kadın Hastalıkları ve Doğum Kliniği, İzmir
Correspondence

Halil Gürsoy Pala, Sağlık Bilimleri Üniversitesi Tepecik Eğitim ve Araştırma Hastanesi, Kadın Hastalıkları ve Doğum Kliniği, İzmir, [email protected]

Publication History

Manuscript Received: December 06, 2016

Manuscript Accepted: December 18, 2016

Earlyview Date: December 18, 2016

Conflicts of Interest

Conflicts of Interest: No conflicts declared.

Objective
The aim of this study was to evaluate the effect of fetal gender in placental volume and the placental mean gray value assessed by three-dimensional (3D) ultrasonography.
Methods
This case-control prospective study consisted of 60 healthy singleton pregnancies, 29 of which were male fetuses and 31 of which were female fetuses, matched for gestational age, maternal age and parity. Placental volume and placental volumetric mean gray values were evaluated. Umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices were calculated.
Results
Placental volume was 296.93±108.08 and 399.12±135.08 cm3 in male and female groups, respectively (p=0.012). Mean gray value of the placenta was 39.68±7.83 and 39.27±7.22 in male and female groups, respectively (p=0.863). UA pulsatility index (PI) was 1.03±0.21 and 1.00±0.24 in male and female groups (p=0.761) and MCA PI was 1.84±0.85 and 2.16±0.67 in male and female groups, respectively (p=0.197). Correlation analysis revealed that placental volume was not correlated with the fetal weight at the time of delivery (r=0.224, p=0.164). There was negative significant relation between placental volume and UA PI (r=-0.401, p=0.006).
Conclusion
Female fetuses have larger placental volumes which may contribute to get better results through the adverse maternal environmental conditions.
Keywords

Placental volume, 3D ultrasonography, gender-specific difference, VOCAL analysis.

Introduction
New concept for analyzing the pregnancy physiology better will probably include defining fetal gender.[1] Previous studies already showed that fetal gender was related with various complications of pregnancy; the male fetuses had complications associated with defective placentation such as preeclampsia and ablatio placenta. Besides, preterm delivery and postterm pregnancy were more common in male fetuses whereas hyperemesis gravidarum and placental invasion anomalies were more common in female fetuses.[2–7] Moreover, detection of fetal Y-chromosomal sequences as early as 15–16 weeks of gestation has presented the opportunity to define preeclampsia before clinical syndrome occurs.[8,9] In addition, male fetuses had increased rates of cesarean section and intrapartum fetal distress.[10]
Maternal serum human chorionic gonadotropine (hCG) levels differed according to the fetal gender and were increased more prominantly in male fetuses.[11,12] Increased maternal serum hCG levels were found to be associated with lower angiogenin levels in the amniotic fluid, which suggested inadequate angiogenesis in male fetuses.[13] Steier et al. hypothesized that hCG metabolism differed according to the fetal sex and showed that hCG elimination after delivery was different in male and female newborns. During the first hour after the delivery, hCG eliminated more rapidly if the newborn was male.[14]
Few studies conducted in order to discover any association between placental histology and fetal gender. Regarding preeclamptic placentas, Naeye et al. showed that female fetuses had excessive syncytial knots as a consequence of low uteroplacental blood flow. With this finding, they suggested that male fetuses caused a greater maternal blood plasma volume expansion.[15] Regarding preterm deliveries before 32 weeks of gestation, male gender was shown to be related with chronic inflammatory placental lesions which were suggestive for the maternal immune response against the trophoblastic invasion.[16]
The aim of this study was to evaluate the effect of fetal gender in placental volume and placental mean gray value assessed by three-dimensional (3D) ultrasonograghy.
Methods
This prospective case-control study consisted of 60 pregnancies who had ultrasound examinations between January 2013 and June 2014 at our Perinatology Outpatient Clinic. Institutional Ethics Committee approved the study.
The study population consisted of 60 healthy singleton pregnancies during their third trimester and was assigned into two groups as male and female fetuses matched for the week of gestation and maternal age. The male group consisted of 29 healthy singleton pregnancies between 24 and 40 weeks of gestation (mean: 33.88±4.41 weeks). The female group included 31 singleton pregnancies aged between 24 and 40 weeks of gestation (mean: 31.71±3.77 weeks). The inclusion criteria were (1) the cases whose entire placenta could be seen and (2) the gender of the fetus defined by sonographic examination.
Gestational age was evaluated with the last menstrual period and confirmed by the early first trimester ultrasonography scans. Multiple pregnancies, women with chronic systemic disease such as diabetes, vasculitis, connective tissue disorder, hypertension/preeclampsia, hepatic or renal failure, and pregnancies with fetal chromosomal or structural anomaly were excluded from the study.
Ultrasound examinations were performed using a Voluson 730 Pro system with a RAB 3.5-MHz array probe with a combination of power Doppler and 3D/4D properties (GE Medical Systems, Milwaukee, WI, USA). All examinations were carried out via transabdominal probe by the same operator (H.G.P.). At that time, the other operator (B.A.U.) was observing the entire placenta scan and measurements independently.
2D gray scale ultrasound examinations were performed for all patients in the study group for evaluating fetal biometric measurements and placental localization according to Hadlock et al.[17] After the visualization of the entire placenta, we performed a 3D scanning with the widest scanning angle (80°). After scanning the region of interest (ROI), we used Virtual Organ Computer-aided Analysis (VOCAL-II) imaging software to assess the placental volume (cm3) (VOCAL settings: manual trace, rotation angle: 30°)[18,19] (Fig. 1). The mean gray value represented the videodensity of the placenta as presented on the computer screen. It is expressed as a percentage with a minimum value being 0 (minimum videodensity) and maximum value being 100 (maximum videodensity)[20,21] (Fig. 2).
Umbilical artery (UA) Doppler measurements were obtained in the free loop.[22] Fetal mid-cerebral artery Doppler evaluation was made by obtaining a fetal axial section including fetal thalamic nuclei on the scan. Color flow mapping was used to identify the circle of Willis. The measurement was made on the proximal third of the middle cerebral artery (MCA) where it is close to its origin in the internal carotid artery.[23] All Doppler waveforms were calculated only after obtaining three consecutive waveforms.
Statistical analysis was performed by using SPSS v.20 (SPSS Inc., Chicago, IL, USA). The results were expressed in mean ± standard deviation (SD). A p value less than 0.05 was regarded as statistically significant. Student’s t-test for unpaired variables was used to evaluate the group differences. Spearman’s correlation analysis was conducted to investigate the relation between placental volume, mean gray values of the placenta, Doppler results and the week of gestation.
Results
Mean maternal age was 31.88±5.16 weeks and 29.14±6.21 weeks in male and female groups, respectively (p=0.162). Mean gestational age was 33.88±4.41 weeks and 31.71±3.77 weeks in male and female groups, respectively (p=0.111). Placental volume was 296.93± 108.08 cm3 and 399.12±135.08 cm3 in male and female groups, respectively (p=0.012) (Fig. 3). Mean gray value of the placenta was 39.68±7.83% and 39.27±7.22% in male and female groups, respectively (p=0.863). UA pulsatility index (PI) was 1.03±0.21 and 1.00±0.24 in male and female groups (p=0.761) and MCA PI was 1.84± 0.85 and 2.16±0.67 in male and female groups, respectively (p=0.197) (Table 1).
Correlation analysis revealed that placental volume was not correlated with the fetal weight at the time of delivery (r=0.224, p=0.164). There was negative significant relation between placental volume and UA PI (r= -0.401, p=0.006); UA resistance index (r=-0.423, p=0.002); and UA systole/diastole ratio (r=-0.370, p= 0.006). Placental volume was not associated with parity, week of gestation, and mean gray value (r=0.175, p= 0.111; r=0.140, p=0.135; r=-0.025, p=0.783, respectively) (Table 2).
Discussion
Recent studies have suggested that the placental functions differ according to the fetal gender.[1,24,25] Female and male fetuses develop through different mechanisms to get through the same adverse maternal environment in utero. Female placenta typically makes adjustments for longer survival if any adverse environmental change occurs.[1] Even vascularity and angiogenesis develop in a gender-different manner.[16] From that point of view, we hypothesized that placental volume and histogram may have changed regarding the fetal sex. Our study group comprised of the uncomplicated singleton pregnancies. Female placental volumes were significantly larger, although the measurements were performed approximately one week earlier in female fetuses. Our study is the first one evaluating the placental volume and mean gray value according to fetal gender.
Previous studies showed that male fetuses had poorer placentation, poorer angiogenesis and poorer adaptation mechanisms to adverse maternal conditions.[1,16] Recently, Prior et al. evaluated 388 term pregnancies and reported reduced MCA resistance and umbilical venous flow rates without any significant difference in UA PI in male fetuses[26] Similarly, we found lower MCA PI in males; however this difference has not reached to a statistically significant level. UA PI was also similar in both sexes (p=0.897). Prior et al. suggested that lower resistance in cerebral circulation in male fetuses may be a fine clue of the in-utero adaptation to the poor placentation.[26]
Placental volume may be a clue for healthy pregnancy, as recent studies showed that placental volume decreased in placental insufficiencies such as preeclampsia and intrauterine growth retardation and increased in gestational diabetes mellitus.[18,27–32] We found that male fetuses had significantly smaller placental volumes which may be a subtle suggestion for poorer placentation in males. However, our sample size –one of the limitation of our study– was relatively small and although our preliminary results show significant difference, this finding must be confirmed with larger studies. The other interesting preliminary result of our study was the indifference of volumetric mean gray value in both genders. Mean gray value describes the videodensity of the placenta; increased mean gray value means increased calcific tissue and decreased vascularity. Regarding both genders, we found no difference. The other limitation of our study was the lack of the data about the smoking status of the pregnant women participated in the study. Recent studies showed that smoking status had no effect on the placental volume.[33,34] However, it may have an effect on the placental angiogenesis and volumetric mean gray values. In the other hand, the advantage of our study was the matched groups for the gestational age, parity and maternal age.
Conclusion
In conclusion, our preliminary results, as the new findings in the literature, showed that male fetuses had significantly smaller placental volumes which may be associated with poorer placentation. This must be confirmed with larger studies.
References
  1. Clifton VL. Review: Sex and the human placenta: mediating differential strategies of fetal growth and survival. Placenta 2010;31 Suppl:S33–9. [PubMed] [CrossRef

  2. Askling J, Erlandsson G, Kaijser M, Akre O, Ekbom A. Sickness in pregnancy and sex of child. Lancet 1999;354:2053. [PubMed] [CrossRef

  3. Cooperstock M, Campbell J. Excess males in preterm birth: interactions with gestational age, race and multiple birth. Obstet Gynecol 1996;88:189–93. [PubMed] [CrossRef

  4. Divon MY, Ferber A, Nisell H, Westgren M. Male gender predisposes to prolongation of pregnancy. Am J Obstet Gynecol 2002;187:1081–3. [PubMed] [CrossRef

  5. James WH. Why are boys more likely to be preterm than girls? Plus other related conundrums in human reproduction. Hum Reprod 2000;15:2108–11. [PubMed] [CrossRef

  6. James WH. Sex ratios of offspring and the causes of placental pathology. Hum Reprod 1995;10:1403–6. [PubMed] [CrossRef

  7. McGregor JA, Leff M, Orleans M, Baron A. Fetal gender differences in preterm birth: findings in a North American cohort. Am J Perinatol 1992;9:43–8. [PubMed] [CrossRef

  8. Alberry MS, Maddocks DG, Hadi MA, Metawi H, Hunt LP, Abdel-Fattah SA, et al. Quantification of cell free fetal DNA in maternal plasma in normal pregnancies and in pregnancies with placental dysfunction. Am J Obstet Gynecol 2009;200:98.e1–6. [PubMed] [CrossRef

  9. Cotter AM, Martin CM, O’leary JJ, Daly SF. Increased fetal DNA in the maternal circulation in early pregnancy is associated with an increased risk of preeclampsia. Am J Obstet Gynecol 2004;191:515–20. [PubMed] [CrossRef

  10. Bekedam DJ, Engelsbel S, Mol BWJ, Buitendijk SE, van der Pal-de Bruin KM. Male predominance in fetal distress during labor. Am J Obstet Gynecol 2002;187:1605–7. [PubMed] [CrossRef

  11. Bazzett LB, Yaron Y, O’Brien JE, Critchfield G, Kramer RL, Ayoub M, et al. Fetal gender impact on multiple-marker screening results. Am J Med Genet 1998;76:369–71. [PubMed] [CrossRef

  12. Leporrier N, Herrol M, Leymarie P. Shift of the fetal sex ratio in hCG selected pregnancies at risk for Down syndrome. Prenat Diagn 1992;12:703–4. [PubMed] [CrossRef

  13. Spong CY, Ghidini A, Dildy GA, Loucks CA, Varner MW, Pezzullo JC. Elevated second-trimester maternal serum hCG: a marker of inadequate angiogenesis. Obstet Gynecol 1998;91:605–8. [PubMed

  14. Steier JA, Bergsjø PB, Myking OL. Disappearance of human chorionic gonadotropin after cesarean section with regard to fetal sex. Acta Obstet Gynecol Scand 2002;81:403–6. [PubMed] [CrossRef

  15. Naeye RL, Demers LM. Differing effects of fetal sex on pregnancy and its outcome. Am J Med Genet Suppl 1987;3:67–74. [PubMed

  16. Ghidini A, Salafia CM. Gender differences of placental dysfunction in severe prematurity. BJOG 2005;112:140–4. [PubMed] [CrossRef

  17. Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK. Estimation of fetal weight with the use of head, body and femur measurements-a prospective study. Am J Obstet Gynecol 1985;151:333–7. [PubMed] [CrossRef

  18. Pomorski M, Zimmer M, Florjanski J, Michniewicz J, Wiatrowski A, Fuchs T, et al. Comparative analysis of placental vasculature and placental volume in normal and IUGR pregnancies with the use of three-dimensional Power Doppler. Arch Gynecol Obstet 2012;285:331–7. [PubMed] [CrossRef

  19. Pala HG, Artunc Ulkumen B, Uyar Y, Koyuncu FM, Bulbul Baytur Y. Three-dimensional placental volume and mean grey value: normal ranges in a Turkish population and correlation with maternal serum biochemistry and Doppler parameters. J Obstet Gynaecol 2014;35:259–62. [PubMed] [CrossRef

  20. Zalud I, Shaha S. Three-dimensional sonography of the placental and uterine spiral vasculature: influence of maternal age and parity. J Clin Ultrasound 2008;36:391–6. [PubMed] [CrossRef

  21. Zalud I, Shaha S. Placental and spiral artery volume and gray-scale value assessment via 3-dimensional sonography in the second trimester. J Clin Ultrasound 2007;35:504–8. [PubMed] [CrossRef

  22. Burrel SJ, Kingdom JC. The use of umbilical artery Doppler ultrasonography in modern obstetrics. Curr Opin Obstet Gynecol 1997;9:370–4. [PubMed

  23. Bhide A, Acharya G, Bilardo CM, Brezinka C, Cafici D, Hernandez-Andrade E, et al. ISUOG Practice Guidelines: use of Doppler ultrasonography in obstetrics. Ultrasound Obstet Gynecol 2013;41:233–9. [PubMed] [CrossRef

  24. Di Renzo GC, Rosati A, Sarti RD, Cruciani L, Cutuli AM. Does fetal sex affect pregnancy outcome? Gend Med 2007;4:19–30. [PubMed] [CrossRef

  25. Vatten LJ, Skjaerven R. Offspring sex and pregnancy outcome by length of gestation. Early Hum Dev 2004;76:47–54. [PubMed] [CrossRef

  26. Prior T, Wild M, Mullins E, Bennett P, Kumar S. Sex specific differences in fetal middle cerebral artery and umbilical venous Doppler. Plos One 2013;8:e56933. [PubMed] [CrossRef

  27. Artunc Ulkumen B, Pala HG, Uyar Y, Koyuncu FM, Bulbul Baytur Y. The assessment of placental volume and mean gray value in preeclamptic placentas by using three-dimensional ultrasonography. J Matern Fetal Neonatal Med 2015;28:1010– 3. [PubMed] [CrossRef

  28. Chen CY, Wang KG, Chen CP. Alteration of vascularization in preeclamptic placentas measured by three-dimensional power Doppler ultrasound. J Matern Fetal Neonatal Med 2013;26:1616–22. [PubMed] [CrossRef

  29. Odibo AO, Goetzinger KR, Huster KM, Christiansen JK, Odibo L, Tuuli MG. Placental volume and vascular flow assessed by 3D power Doppler and adverse pregnancy outcomes. Placenta 2011;32:230–4. [PubMed] [CrossRef

  30. Rizzo G, Capponi A, Cavicchioni O, Vendola M, Arduini D. First trimester uterine Doppler and three-dimensional ultrasound placental volume calculation in predicting pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 2008;138:147– 51. [PubMed] [CrossRef

  31. Artunc Ulkumen B, Pala HG, Uyar Y, Koyuncu FM, Bulbul Baytur Y. The alteration in placental volume and placental mean grey value in growth-restricted pregnancies assessed by 3D ultrasound (Growth Restriction & 3D Ultrasonography). J Obstet Gynaecol 2015;35:447–50. [PubMed] [CrossRef

  32. Pala HG, Artunc Ulkumen B, Koyuncu FM, Bulbul Baytur Y. Three-dimensional ultrasonographic placental volume in gestational diabetes mellitus. J Matern Fetal Neonatal Med 2016;29:610–4. [PubMed] [CrossRef

  33. Jauniaux E, Suri S, Muttukrishna S. Evaluation of the impact of maternal smoking on ultrasound and endocrinological markers of first trimester placentation. Early Hum Dev 2013;89:777–80. [PubMed] [CrossRef

  34. Rizzo G, Capponi A, Pietrolucci ME, Arduini D. Effects of maternal cigarette smoking on placental volume and vascularization measured by 3-dimensional power Doppler ultrasonography at 11+0 to 13+6 weeks of gestation. Am J Obstet Gynecol 2009;200:415.e1–5. [PubMed] [CrossRef
File/Dsecription
Fig. 1.
Assessment of placental volume by VOCAL method.
Fig. 2.
Assessment of the mean gray value.
Fig. 3.
Placental volume assessed by 3D ultrasonography in male and female fetuses.
Table 1.
Clinical data in healthy singleton Turkish pregnancies with male and female fetuses.
Table 2.
Correlation analysis of placental volume with the week of gestation, parity, umbilical artery PI, placental mean gray value and birth weight.