Sonographic assessment of fetal testicular development and descent

Sonographic assessment of fetal testicular development and descent | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Sonographic assessment of fetal testicular development and descent Aya Shirakawa, Toshiyuki Yasui, Ayuka Mineda, Atsuko Yoshida, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5932486/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective The aim of this report is to describe techniques and to provide basic and available scientific data on the success of testicular size procedures. Methods In this prospective longitudinal study, 186 normal fetuses from 23 weeks of gestation were followed up by ultrasonography. We assessed the testis descent in the scrotum and measured the major (mm) and minor (mm) axes of the testes in the scrotum in fetuses, as well as the height in newborn infants. Testicular sizes were compared among five periods (23-26 weeks, 27-30 weeks, 31-34 weeks, ≥35weeks, and neonatal period). Results The testicular cross-sectional area increased exponentially with gestational age. The cross-sectional area of each testis in fetuses at ≥35 weeks was very similar to that in newborn infants. In both the testes, the fetal testicular cross-sectional area at ≥35 weeks was strongly correlated with the neonatal testicular volume. At 27-30 weeks, the testicular cross-sectional areas of the descended testes in fetuses with unilaterally undescended testis were significantly smaller than those in fetuses with both descended testes. Conclusion We provide basic data of fetal testis size and useful way to measure testes size available. Health sciences/Medical research/Outcomes research Health sciences/Endocrinology/Endocrine system and metabolic diseases/Gonadal disorders/Hypogonadism Health sciences/Urology/Paediatric urology fetal testicular size ultrasonography undescended testis Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction In the first trimester until around 10 weeks, the formation of external genitalia and masculinization is stimulated by androgens induced by hCG (human Chorionic Gonadotropin) with the peak of this process influencing gonadal differentiation and gender identity. 1 , 2 From the second to the third trimester of gestation, the GnRH (Gonadotropin-releasing hormone) neuronal system becomes functional, leading to genesis of testosterone, which promotes the development of the penis and testes, and the descent of the testes from the abdominal cavity into the scrotum. 3 Testosterone concentration level initially decreases after birth, however, one-week-old to a-few-months-old infants produce hormone again due to the GnRH neuronal system. 1 , 3 This results in an increase in the secretion of FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone), and sex hormones comparable to that during puberty, which is considered important for the proliferation of Sertoli cells and germ cells, the development of external genitalia, and the future formation of sperm, called mini-puberty. 1 , 4 , 5 Penis and testes grow up due to testosterone in this period, too. 5 That is to say, deficiency of testosterone cause to micropenis, cryptorchidism and small testes at fetal to mini-puberty period. 3 These are good periods to estimate hypothalamus-pituitary-gonadal system before puberty. 5 Fetal blood sampling is technically challenging, therefore, such as testicular sizes are used to assess the gonadal dysfunction. However, there are no decisive databases of small testes during the fetal to newborn infants. In the past reports of testes size, the prepubertal size is 2–4 ml, 6 and less than 1ml of the testicular volume, it suggests the possibility of disorder of sexual differentiation or androgen synthesis disorders due to hypogonadotropic hypogonadism at any age before puberty. Testicular volume is positively correlated with total testosterone and sperm concentration in infertile men. 7 – 9 Thus testicular size is considered a clinical marker of hormonal and spermatogenic function, the assessment of testicular size especially from the fetal to the neonatal period is important. Several studies have used ultrasonography to assess testicular development. 10 – 13 However, there are few reports on the development of testicular size during the fetal period using ultrasonography. A cross-sectional study reported that the testicular diameter measured using ultrasonography in fetuses between 20 and 40 weeks of gestation showed a significant positive correlation with gestational age. 14 In a cross-sectional prospective study, Achiron et al. reported that testicular circumference in 210 fetuses between 14 and 37 weeks of gestation increased with gestational age. 15 To the best of our knowledge, no prospective longitudinal study of fetal testicular size using ultrasonography from the fetal to neonatal period has been conducted. Based on our technique for measuring testicular size in newborn infants using ultrasonography, 13 we considered that it is possible to measure the major (mm) and minor (mm) axes of the testes in fetuses accurately and regularly. Furthermore, we hypothesized that a prospective longitudinal study would allow us to examine the association between fetal testicular cross-sectional area and actual testicular volume in newborns. This is the first prospective, longitudinal study of testicular size development and descent from the fetal to neonatal period using ultrasonography. Statistical analyses The differences between the testicular cross-sectional area in fetuses with both testes descent and unilateral descent were analyzed by the Mann–Whitney U test. Differences in the major axis, minor axis, and cross-sectional area between the right and left testes were also analyzed using the Mann–Whitney U test. The correlation between the testicular cross-sectional areas at each period was analyzed using Spearman’s rank correlation test. A p-value < 0.05 was considered significant. Results To assess the reliability of testicular size measurements using ultrasonography, measurements were performed on eight randomly selected fetuses and infants not included in this study prior to the initiation of the study. The intraclass correlation coefficients of length and width were 0.92 and 0.96, respectively, in the right testis of the fetus, and 0.98 and 0.95 in the left testis of the fetus. The interclass correlation coefficients of length and width were 0.97 and 0.96, respectively, in the right testis of the fetus, and 0.98 and 0.86 in the left testis of the fetus. For testicular volume in newborn infants, the intraclass correlation coefficients of length, width, and height were 0.93, 0.91, and 0.76, respectively, in the right testis, and 0.76, 0.86, and 0.77 in the left testis. 13 A flowchart of the longitudinal study is shown in Fig. 2 . We measured the testicular size in fetuses with confirmed testicular descent. In some fetuses, we could not measure the testicular cross-sectional area owing to the fetal position in the uterus. At recruitment, the mean ± standard deviation (SD) gestational period was 179.1 ± 8.1 days in 186 fetuses. Maternal and paternal ages were 34.4 ± 5.2 (range, 20–45) and 34.8 ± 5.9 (22–57) years, respectively. The number of primiparous and multiparous women was 85 and 101, respectively. Before pregnancy, maternal body height, weight, and BMI were 158.2 ± 5.3 cm, 54.8 ± 9.5 kg, and 21.8 ± 3.4 kg/m 2 , respectively. The number of women with a smoking habit before pregnancy was five (2.7%), but no one had this habit during pregnancy. The number of women with pregestational and gestational diabetes was 5 (2.7%) and 15 (8.1%), respectively. Nine (5.8%) women received insulin treatment. Pregestational and gestational hypertension were present in 3 (1.6%) and 20 (10.8%) women, respectively. Testicular descent was found earliest at 24w4d (left side) of gestational age. At less than 27 weeks, only 7% of fetuses had both testes descended into the scrotum. At 27–30 weeks, 80% of fetuses had both testes descended, and 95% had at least one of them descended. Approximately 100% of fetuses had the testes descended from 31 weeks of gestation. At 27–30 weeks, the testicular cross-sectional area on the contralateral side in fetuses with an undescended testis was significantly smaller than that in fetuses with both the testes descended (Fig. 3 ; p = 0.0014 on the right side and p = 0.036 on the left side). The development of the right and left testicular cross-sectional areas based on the gestational age is shown in Fig. 4 . Each testicular cross-sectional area increased exponentially with gestational age. The mean cross-sectional areas of the right and left testes at each of the five periods (23–26 weeks, 27–30 weeks, 31–34 weeks, ≥ 35 weeks, and neonatal period) were as follows: A:14.7 ± 4.8 mm 2 /14.9 ± 4.8 mm 2 , B:25.6 ± 8.1 mm 2 /26.0 ± 8.5 mm 2 , C:38.0 ± 10.0 mm 2 /38.4 ± 9.7 mm 2 , D:50.1 ± 12.3 mm 2 /49.5 ± 11.7 mm 2 , E:50.8 ± 9.6 mm 2 /50.5 ± 9.2 mm 2 . The cross-sectional area of each testis in fetuses at ≥ 35 weeks was very similar to that in newborn infants. No significant differences were observed in the major axis, minor axis, or cross-sectional area between the right and left testes. The correlations between the right and left testicular cross-sectional areas in each fetus were r = 0.75, p = 0.004 at 23–26 weeks; r = 0.82, p < 0.001 at 27–30 weeks; r = 0.72, p < 0.01 at 31–34 weeks; r = 0.78, p < 0.001 at ≥ 35 weeks; and r = 0.72, p < 0.01 in newborn infants. The testicular cross-sectional areas in fetuses at ≥ 35 weeks were moderately correlated with these in newborn infants in both the right and left testes (r = 0.42, p < 0.01, and r = 0.46, p < 0.01, respectively), and with the testicular volume in newborn infants in both the right and left testes as well (r = 0.47, p < 0.01, and r = 0.44, p 80%, the association between testicular size and maternal background, fetal developmental parameters, and newborn infants’ parameters was examined (Table 1– 1 , 1 –2, 1 –3). Table 1 1 . Comparison of parameters according to testicular cross-sectional area at 27–30 weeks Right (115) Left (115) Small (57) Large (58) p value Small (57) Large (58) p value Mean testicular cross-sectional area (mm 2 ) 18.9 ± 3.8 32.3 ± 5.1 19.0 ± 4.4 33.1 ± 5.2 Maternal age, years 33.7 ± 5.5 34.6 ± 5.1 0.40 34.0 ± 5.8 34.4 ± 5.0 0.82 Paternal age, years 34.9 ± 6.1 34.9 ± 6.0 0.73 34.5 ± 7.0 35.0 ± 4.9 0.76 Body weight before pregnancy (kg) 52.9 ± 9.9 56.1 ± 7.4 0.017 53.9 ± 10.1 54.6 ± 8.0 0.27 BMI before pregnancy (kg/m 2 ) 21.2 ± 3.4 22.1 ± 2.7 0.059 21.4 ± 3.5 21.8 ± 2.9 0.31 Body weight at period B (kg) 58.9 ± 9.2 62.7 ± 7.2 < 0.01 60.2 ± 9.4 60.8 ± 7.9 0.38 BMI at period B (kg/m 2 ) 23.7 ± 3.1 24.7 ± 2.8 0.021 24.0 ± 3.2 24.3 ± 2.9 0.36 Weight gain until period B (kg) 6.0 ± 2.8 6.7 ± 3.0 0.42 6.3 ± 3.0 6.3 ± 2.7 0.77 Increase in BMI until period B (kg/m 2 ) 2.4 ± 1.1 2.6 ± 1.2 0.57 2.5 ± 1.2 2.5 ± 1.1 0.89 EFBW at period B 1379.6 ± 177.2 1501.0 ± 166.6 < 0.01 1414.8 ± 186.7 1464.5 ± 167.3 0.061 Maternal body height 157.5 ± 5.8 159.3 ± 5.2 0.087 158.3 ± 5.5 158.1 ± 5.6 1.0 Placental weight (g) 572.8 ± 85.0 600.7 ± 122.6 0.19 566.3 ± 88.5 581.9 ± 127.2 0.48 Body weight in newborn infants (g) 3131.6 ± 297.9 3141.7 ± 399.1 0.79 3085.1 ± 317.3 3108.7 ± 442.6 0.51 Length in newborn infants (cm) 49.8 ± 1.6 49.8 ± 1.8 0.96 49.5 ± 1.7 49.8 ± 1.9 0.69 Proportion of nulliparous 59.6% (34/57) 36.2% (21/58) 0.012 52.6% (30/57) 39.7% (23/58) 0.16 DM 10.5% (6/57) 6.9% (4/58) 0.49 5.3% (3/57) 6.9% (4/58) 0.71 HT 7.0% (4/57) 8.6% (5/58) 0.75 7.0% (4/57) 6.9% (4/58) 0.98 BMI: body mass index, EFBW: estimated fetal body weight DM: diabetes mellitus (prediabetes, gestational diabetes, and/or insulin treatment) HT: hypertension including hypertension before pregnancy or preeclampsia Table 1 2. Comparison of parameters according to testicular cross-sectional area at 31–34 weeks Right (129) Left (128) Small (65) Large (64) p value Small (64) Large (64) p value Mean testicular cross-sectional area (mm 2 ) 40.4 ± 6.8 59.9 ± 8.1 39.9 ± 6.0 46.2 ± 6.0 Maternal age, years 34.1 ± 5.0 34.1 ± 4.8 0.93 33.9 ± 5.1 33.6 ± 5.5 0.32 Paternal age, years 34.2 ± 5.7 34.6 ± 5.4 0.61 34.7 ± 6.1 34.4 ± 6.7 0.86 Body weight before pregnancy (kg) 54.7 ± 10.2 54.2 ± 8.6 0.84 54.1 ± 9.8 53.8 ± 7.8 0.56 BMI before pregnancy (kg/m 2 ) 21.8 ± 3.7 21.6 ± 3.1 0.95 21.6 ± 3.5 21.5 ± 2.9 0.82 Body weight at period C (kg) 63.3 ± 10.0 63.8 ± 8.8 0.58 63.2 ± 9.9 61.7 ± 8.0 0.49 BMI at period C (kg/m 2 ) 24.9 ± 3.0 25.2 ± 3.3 0.49 24.9 ± 3.0 25.0 ± 3.5 0.32 Weight gain until period C (kg) 8.6 ± 3.1 9.6 ± 3.3 0.13 9.1 ± 3.0 7.9 ± 2.9 0.21 Increase in BMI until period C (kg/m 2 ) 3.1 ± 3.1 3.7 ± 2.9 0.16 3.2 ± 3.3 3.1 ± 3.9 0.23 EFBW at period C 2658.9 ± 444.5 2774.5 ± 296.7 0.12 2699.1 ± 291.8 2181.0 ± 289.6 0.035 Maternal body height 158.1 ± 5.4 158.4 ± 5.3 1 157.9 ± 5.8 158.1 ± 5.7 0.83 Placental weight (g) 563.0 ± 102.7 594.0 ± 104.9 0.098 567.1 ± 100.8 593.3 ± 100.5 0.086 Body weight in newborn infants (g) 3081.2 ± 350.0 3213.7 ± 340.5 0.028 3105.2 ± 358.1 3168.2 ± 359.7 0.56 Length in newborn infants (cm) 49.6 ± 1.7 50.1 ± 1.3 0.05 49.8 ± 1.7 49.8 ± 1.5 0.97 Proportion of nulliparous 42.4% (28/66) 42.4% (28/66) 1 44.4% (28/63) 40.6% (26/64) 0.21 DM 10.6 % (7/66) 3.0% (2/66) 0.080 7.9% (5/63) 3.1% (2/64) 0.14 HT 4.5 % (3/66) 9.1% (6/66) 0.30 4.8% (3/63) 6.3% (4/64) 0.70 BMI: body mass index, EFBW: estimated fetal body weight DM: diabetes mellitus (prediabetes, gestational diabetes, and/or insulin treatment) HT: hypertension including hypertension before pregnancy or preeclampsia Table 1 3. Comparison of parameters according to testicular cross-sectional area more than 35 weeks Right (132) Left (126) Small (66) Large (66) p value Small (63) Large (63) p value Mean testicular cross-sectional area (mm 2 ) 40.4 ± 6.8 59.9 ± 8.1 39.9 ± 6.0 59.0 ± 7.5 Maternal age, years 34.1 ± 5.0 34.1 ± 4.8 0.93 33.9 ± 5.1 34.4 ± 4.4 0.76 Paternal age, years 34.2 ± 5.7 34.6 ± 5.4 0.61 34.7 ± 6.1 34.1 ± 4.9 0.59 Body weight before pregnancy (kg) 54.7 ± 10.2 54.2 ± 8.6 0.84 54.1 ± 9.8 55.2 ± 9.2 0.23 BMI before pregnancy (kg/m 2 ) 21.8 ± 3.7 21.6 ± 3.1 0.95 21.6 ± 3.5 21.9 ± 3.3 0.32 Body weight at period D (kg) 63.3 ± 10.0 63.8 ± 8.8 0.58 63.2 ± 9.9 64.1 ± 8.9 0.35 BMI at period D (kg/m 2 ) 24.9 ± 3.0 25.2 ± 3.3 0.49 24.9 ± 3.0 25.3 ± 3.3 0.38 Weight gain until period D (kg) 8.6 ± 3.1 9.6 ± 3.3 0.13 9.1 ± 3.0 8.9 ± 3.4 0.78 Increase in BMI until period D (kg/m 2 ) 3.1 ± 3.1 3.7 ± 2.9 0.16 3.2 ± 3.3 3.4 ± 2.7 0.93 EFBW at period D 2658.9 ± 444.5 2774.5 ± 296.7 0.12 2699.1 ± 291.8 2715.5 ± 458.1 0.34 Maternal body height 158.1 ± 5.4 158.4 ± 5.3 1 157.9 ± 5.8 158.5 ± 4.9 0.58 Placental weight (g) 563.0 ± 102.7 594.0 ± 104.9 0.098 567.1 ± 100.8 590.4 ± 104.5 0.20 Body weight in newborn infants (g) 3081.2 ± 350.0 3213.7 ± 340.5 0.028 3105.2 ± 358.1 3210.9 ± 324.9 0.14 Length in newborn infants (cm) 49.6 ± 1.7 50.1 ± 1.3 0.05 49.8 ± 1.7 50.0 ± 1.3 0.54 Proportion of nulliparous 42.4% (28/66) 42.4% (28/66) 1 44.4% (28/63) 38.1% (24/63) 0.47 DM 10.6% (7/66) 3.0% (2/66) 0.080 7.9% (5/63) 4.8% (3/63) 0.46 HT 4.5% (3/66) 9.1% (6/66) 0.30 4.8% (3/63) 7.9% (5/63) 0.46 BMI: body mass index, EFBW: estimated fetal body weight DM: diabetes mellitus (prediabetes, gestational diabetes, and/or insulin treatment) HT: hypertension including hypertension before pregnancy or preeclampsia At 27–30 weeks, the right testicular cross-sectional area was significantly correlated with the maternal body weight (p = 0.007) and BMI (p = 0.021) and with the pre-pregnant maternal body weight (p = 0.017). However, these differences were not significant at > 31 weeks of gestation (Table 1– 1 ). At 27–30 weeks and 31–34 weeks, the testicular cross-sectional area and EFBW were positively correlated (Table 1– 1 , 1 –2). At 27–30 weeks, the right testicular cross-sectional area and parity were significantly correlated (Table 1– 1 ). More than 35 weeks, the right fetal testicular cross-sectional area was significantly correlated with the body weight and length in infants (Table 1 –3). The proportion of mothers with diabetes (moderate and severe gestational or pre-gestational diabetes) and HDP was not associated with fetal testicular size at any time point. Discussion This is the first prospective longitudinal study on testicular size from fetuses to newborn infants in Japan using ultrasonography. We clarified that intra-class and inter-class correlation coefficients in testicular sizes were > 0.7 in fetuses and newborn infants. We believe that measurements of testicular size using ultrasonography have high reliability. In a previous study on fetuses, Rotondi et al. reported that the intraobserver repeatability of the measurements was 9.6%, 14 and Achiron et al. reported that intraobserver repeatability, as determined by the coefficient of variation, was 10%. 15 In newborn infants, intra-class correlation coefficients > 0.80 with a minimum of 0.57 are reported. 11 Ultrasonography is a useful tool for measuring fetal and infantile testicular size. In this study, the fetal testicular major axis and minor axis were measured using ultrasonography with liner transducers because they are more accurate than the convex transducers normally used for fetal ultrasound. Since no linear probe is currently capable of 3D measurements, we estimated the testicular cross-sectional areas by measuring two dimensions and indicated a testicular developmental curve of cross-sectional area with gestation. The testicular cross-sectional areas in fetuses at 35 weeks of gestation were similar to those in infants. In addition, the fetal testicular cross-sectional area at ≥ 35 weeks of gestation was correlated with the neonatal testicular volume. Based on these findings, we believe that fetal testicular cross-sectional area can be measured accurately and reliably, and it can be an indicator of the sex hormone environment in utero as well as testicular volume. However, if the resolution of the convex probe for 3D probing is improved in the future, it may be possible to measure the volume of the testis. The study showed that the earliest testicular descent occurred at 24w4d gestation and confirmed that 80% of fetuses have both testes descended into the scrotum between 27 and 30 weeks of gestation, and approximately 100% of fetuses have the testes descended from 31 weeks of gestation in Japan. This result is consistent with those of previous studies. By ultrasonography, Birnholz showed that 62% of fetuses have the testes descended into the scrotum between 28 and 30 weeks, and 93% after 32 weeks. 16 Malas et al. reported that no testes descended into the scrotum until 27 weeks of gestation and that both testes in all fetuses aged 33–40 weeks descended into the scrotum. 17 Rotondi et al. reported that the earliest observation of a descended testis was found in 6.6% at 23 weeks of gestation, and in 98.2% of the fetuses, beyond 32 weeks’ gestation, both testes had descended in the scrotum. 14 Achiron et al. reported that no testes were observed in the scrotum before 25 weeks of gestation, 30% had at least one descended testis at 25 weeks, and bilateral testicular descent was observed in 97% of the cases from 32 weeks onwards. 15 We found that the testicular cross-sectional area was smaller in fetuses with unilaterally descended testes than in those with bilaterally descended testes shortly after the testes descended (27–30 weeks). There are no reports of small testicular size in fetuses with unilaterally descended testes. Physiological testicular descent is regulated by the insulin-like peptide 3 (INSL3) and testosterone. INSL3 plays a role in gubernaculum thickening and retains the testes in the inguinal region. Subsequently, the passage of the testes through the inguinal canal and into the scrotum is largely under androgen control. 18 INSL3 was significantly decreased in the non-palpable testes group compared with the palpable testes group in a previous study. 19 INSL3 and testosterone levels related to testicular descent might be involved in the small testicular size of unilaterally descended testes. In addition to this, it could be considered about spatial pressure in the inguinal canal versus the scrotum. The developmental speeds of various organs during the fetal period are not uniform, and the fetal growth curve differs according to body organs. In a multicenter population-based project, it was reported that the fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. 20 Rotondi et al. reported a linear relationship between testicular diameter and gestational age between 20 and 40 weeks of gestation. 14 Achiron et al. reported an exponential relationship between scrotal circumference and gestational age at 14–37 weeks of gestation. 15 In this longitudinal prospective study, we showed that the testicular cross-sectional area exponentially increases with gestational age. Measurement of prenatal testicular size and diagnosis of undescended testes during the fetal period are beneficial because they allow for the simultaneous detection of additional complications in fetuses. A small testis may suggest several diseases, such as Klinefelter syndrome, Kallmann syndrome, and Y chromosome microdeletions. Cheng et al. reported that 20% of patients with undescended testes had at least one associated anomaly, such as urogenital disorders, gastrointestinal tract anomalies, abdominal wall defects, or cardiovascular anomalies. 21 In addition, we can understand testicular development-related factors in pregnant women by measuring prenatal testicular size. Studies on these factors are also useful for detecting reproductive function after birth. The relationship between maternal smoking and small testicular size in adulthood has been reported. 22 Tartarin et al. found that exposure to metformin during intrauterine life reduced the testicular size in fetuses and neoanates. 23 In the present study, no women currently smoked or used metformin. It has been suggested that women with preeclampsia had lower levels of estrogen and estrogen receptor-α protein and higher levels of testosterone and estrogen receptor-β protein, suggesting their roles in the pathogenesis of preeclampsia. 24 Alsnes et al. reported that testicular volume was higher in boys in the preeclampsia group than in preeclampsia-unexposed boys aged 12 years. 25 In the present study, we did not find an association between testicular size and the proportion of participants with Hypertensive Disorders of Pregnancy (HDP) . This study has some limitations. First, measurement of circulating hormone levels in maternal and cord blood may be needed. INSL3 and testosterone produced by Leydig cells in fetuses are involved in testicular descent and size. In addition, changes in maternal circulating testosterone levels have been observed in pregnant women with smoking habits, 26 HDP. 24 , 27 Additional research is required to explore the relationship between circulating endocrine hormones and the factors influencing testicular development. A study combining maternal circulating testosterone and ultrasonography may also be useful. Second, several participants dropped out because of difficulties in measuring maternal obesity and fetal position in the uterus. This is a potential confounding variable in data collection as maternal factors may have an impact on testicular size and descent. It is unclear if the participants that dropped out were different in BMI/hypertension/any other factors affecting testicular size compared with the participants that remained in the study. Conclusion We constructed a growth curve of the fetal testicular cross-sectional area using ultrasonography in a prospective longitudinal study. Fetal testicular cross-sectional area can be an indicator of the sex hormone environment in utero as well as testicular volume. We found that the testicular cross-sectional area of the descended testes in fetuses with unilaterally undescended testis was significantly smaller than that in fetuses with both descended testes shortly after the testes descended. Materials and Methods Pregnant women whose expected date of delivery was between October 2020 and November 2023 were recruited for this prospective longitudinal study. The exclusion criteria were as follows: fetuses with major anomalies; twin fetuses and fetuses with severe fetal growth restriction; and chromosomal abnormalities. We recruited 189 fetuses at 23–26 weeks of gestation and excluded two fetuses with trisomy 21 and one fetus with agenesis of the corpus callosum; a total of 186 fetuses were followed up in this longitudinal study. Ultrasonography was performed using a Volson E10 (GE Healthcare, Milwaukee, WI, USA) with a 3–8 MHz linear transducer (9L) for fetuses (Fig. 1 ) and a Hi VISION Avius (FUJIFILM, Tokyo, Japan) with a 5–18 MHz linear transducer (EUP-L75) for newborn infants. We assessed the testis descent in the scrotum and measured the major (mm) and minor (mm) axes of the testes in the scrotum in fetuses, as well as the height in newborn infants. Testicular cross-sectional area was calculated using the following formula: length/2 × width/2 × π. Testicular volume in newborn infants was determined using the prolate ellipsoid formula. Betül et al reported that the ellipsoid formulas are reliable in calculating neonatal testicular by ultrasound. 28 All the measurements were performed by the same investigator. Interobserver variability was not calculated because only one observer performed the study. This study was approved by the Institutional Review Board of Tokushima University (approval number: 3433/4264). Written and informed consents were obtained from the study participants and parental guardians of the fetuses. All experimental protocols were designed according to the Declaration of Helsinki’s ethical principles and performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects. Declarations Competing interests The authors declare no conflicts of interest regarding the publication of this paper. Funding The authors received no financial support for this study. Author Contribution A.S. and Y.T. wrote the main manuscript text. A.S. and K.T. performed the ultrasound measurements. A.S. performed the statistical analysis. Y.T., K.T., and I.T. contributed to the interpretation of results and provided feedback. M.A., Y.A., and I.T. critically reviewed the manuscript. All authors have approved the manuscript, agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Acknowledgements The authors appreciate the support and cooperation of the participants of this study. Data Availability The datasets used during the current study are available from the corresponding author upon reasonable request. References Rohayem, J. et al. Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement. Endocr. Rev. 45 , 460–492. https://doi.org/10.1210/endrev/bnae003 (2024). Tapanainen, J., Kellokumpu-Lehtinen, P., Pelliniemi, L. & Huhtaniemi, I. Age-related changes in endogenous steroids of human fetal testis during early and midpregnancy. J. Clin. Endocrinol. Metab. 52 , 98–102. https://doi.org/10.1210/jcem-52-1-98 (1981). Horie, S. et al. 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Sakamoto, H. et al. Relationship between testicular size by ultrasonography and testicular function: measurement of testicular length, width, and depth in patients with infertility. Int. J. Urol. 15 , 529–533. https://doi.org/10.1111/j.1442-2042.2008.02071.x (2008). Nguyen, H. B. et al. Ultrasonic testicular size of 24,440 adult Vietnamese men and the correlation with age and hormonal profiles. Andrologia 54 , e14333. https://doi.org/10.1111/and.14333 (2022). Main, K. M. et al. Larger testes and higher inhibin B Levels in Finnish than in Danish newborn boys. J. Clin. Endocrinol. Metab. 91 . 2732–2737. https://doi.org/10.1210/jc.2005-2443 (2006). Nguyen, R. H. et al. US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activity. Pediatr. Radiol. 41 , 633–642. https://doi.org/10.1007/s00247-010-1895-0 (2011). Kaplan, S. L. et al. Size of testes, ovaries, uterus and breast buds by ultrasound in healthy full-term neonates ages 0–3 days. Pediatr. Radiol. 46 . 1837–1847. https://doi.org/10.1007/s00247-016-3681-0 (2016). Shirakawa, A. et al. Ultrasonographic assessment of testicular volume in Japanese newborn infants. J. Med. Invest. 69 . 256–260. https://doi.org/10.2152/jmi.69.256 (2022). Rotondi, M. et al. Prenatal measurement of testicular diameter by ultrasonography: development of fetal male gender and evaluation of testicular descent. Prenat Diagn. 21 , 112–115. https://doi.org/10.1002/1097-0223(200102)21:23.0.co;2-1 (2001). Achiron, R., Pinhas-Hamiel, O., Zalel, Y., Rotstein, Z. & Lipitz, S. Development of fetal male gender: prenatal sonographic measurement of the scrotum and evaluation of testicular descent. Ultrasound Obstet. Gynecol. 11 , 242–245. https://doi.org/10.1046/j.1469-0705.1998.11040242.x (1998). Birnholz, J. C. Determination of fetal sex. N Engl. J. Med. 309 , 942–944. https://doi.org/10.1056/NEJM198310203091602 (1983). Malas, M. A., Sulak, O. & Oztürk, A. The growth of the testes during the fetal period. BJU Int. 84 , 689–692. https://doi.org/10.1046/j.1464-410x.1999.00272.x (1999). Elamo, H. P., Virtanen, H. E. & Toppari, J. Genetics of cryptorchidism and testicular regression. Best Pract. Res. Clin. Endocrinol. Metab. 36 . 101619. https://doi.org/10.1016/j.beem.2022.101619 (2022). Fénichel, P. et al. Cord blood insulin-like peptide 3 (INSL3) but not testosterone is reduced in idiopathic cryptorchidism. Clin. Endocrinol. (Oxf) 82 . 242–247. https://doi.org/10.1111/cen.12500 (2015). Ohuma, E. O. et al. Fetal growth velocity standards from the fetal growth longitudinal study of the INTERGROWTH-21st Project. Am. J. Obstet. Gynecol. 224 https://doi.org/10.1016/j.ajog.2020.07.054 (2021). 208.e1-208.e18. Cheng, W., Mya, G. H. & Saing, H. Associated anomalies in patients with undescended testes. J. Trop. Pediatr. 42 , 204–206. https://doi.org/10.1093/tropej/42.4.204 (1996). Jensen, T. K. et al. Association of in utero exposure to maternal smoking with reduced semen quality and testis size in adulthood: a cross-sectional study of 1,770 young men from the general population in five European countries. Am. J. Epidemiol. 159 , 49–58. https://doi.org/10.1093/aje/kwh002 (2004). Tartarin, P. et al. Metformin exposure affects human and mouse fetal testicular cells. Hum. Reprod. 27 . 3304–3314. https://doi.org/10.1093/humrep/des264 (2012). Lan, K. C. et al. Levels of sex steroid hormones and their receptors in women with preeclampsia. Reprod. Biol. Endocrinol. 18 . 12. https://doi.org/10.1186/s12958-020-0569-5 (2020). Alsnes, I. V. et al. Maternal preeclampsia and androgens in the offspring around puberty: A follow-up study. PLOS ONE. 11. e0167714 (2016). https://doi.org/10.1371/journal.pone.0167714 Toriola, A. T. et al. Determinants of maternal sex steroids during the first half of pregnancy. Obstet. Gynecol. 118 . 1029–1036. https://doi.org/10.1097/AOG.0b013e3182342b7f (2011). Shen, Y. et al. Serum estradiol to testosterone ratio as a novel predictor of severe preeclampsia in the first trimester. J. Clin. Hypertens. (Greenwich) . 25 , 53–60. https://doi.org/10.1111/jch.14601 (2023). Betül, E. et al. The relationship between ultrasonographically measured testicular volumes and cord blood inhibin B concentrations in healthy term male neonates. Reprod. Biol. 23 . 100786. https://doi.org/10.1016/j.repbio.2023.100786 (2023). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5932486","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":414253609,"identity":"8918e51a-e177-4ae1-9316-a01ae38d3bc0","order_by":0,"name":"Aya Shirakawa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYHACZiCWSAAzPwAxGzspWhhngLQwE6eFAayFmQfOxwP4ZyQ/Nvi5xyJPvv2M4WebX9vk+ZgZGD98zMGtReJGmnFizzOJYoMzOcbSuX23DduYGZglZ27DY83tBOMDPAckEjcw5BhI5/bcZgRqYWPmxaNF/nb654N/gFrm978x/m3Zc9ueoBaD2znGySBbGm7kmEkz/LidSFCL4f03xcYyIIfdeFZm2dtwO7mNmbEZr1/kzhzfLPnmQB3QYcmbb/z4c9t2fnvzwQ8f8XkfATgMGBjbQAzGBqLUAwH7AwaGP8QqHgWjYBSMgpEEAN0BU/3q0UOvAAAAAElFTkSuQmCC","orcid":"","institution":"Tokushima University Graduate School","correspondingAuthor":true,"prefix":"","firstName":"Aya","middleName":"","lastName":"Shirakawa","suffix":""},{"id":414253610,"identity":"42c639fb-4ae2-4e65-a2d9-a73cf538f76b","order_by":1,"name":"Toshiyuki Yasui","email":"","orcid":"","institution":"Tokushima University Graduate School","correspondingAuthor":false,"prefix":"","firstName":"Toshiyuki","middleName":"","lastName":"Yasui","suffix":""},{"id":414253611,"identity":"0ae30f48-88a8-4c71-8acf-69d2f9646c4f","order_by":2,"name":"Ayuka Mineda","email":"","orcid":"","institution":"Tokushima University Graduate School","correspondingAuthor":false,"prefix":"","firstName":"Ayuka","middleName":"","lastName":"Mineda","suffix":""},{"id":414253613,"identity":"fcac02b5-2d0e-4060-a988-9a6528cc7d82","order_by":3,"name":"Atsuko Yoshida","email":"","orcid":"","institution":"Tokushima University Graduate School","correspondingAuthor":false,"prefix":"","firstName":"Atsuko","middleName":"","lastName":"Yoshida","suffix":""},{"id":414253625,"identity":"4be5bea7-65db-429b-80b6-ac888f89eebe","order_by":4,"name":"Takeshi Iwasa","email":"","orcid":"","institution":"Tokushima University Graduate School","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Iwasa","suffix":""},{"id":414253626,"identity":"ec98db8f-e2a8-4226-afe2-9f4b14810456","order_by":5,"name":"Takashi Kaji","email":"","orcid":"","institution":"Tokushima University Graduate School","correspondingAuthor":false,"prefix":"","firstName":"Takashi","middleName":"","lastName":"Kaji","suffix":""}],"badges":[],"createdAt":"2025-01-30 20:08:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5932486/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5932486/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":76752551,"identity":"596bf90b-b116-466a-b69b-20fa7bbc2489","added_by":"auto","created_at":"2025-02-20 10:09:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1123934,"visible":true,"origin":"","legend":"\u003cp\u003eUltrasonographic measurements of the testicular size in a fetus at 32 weeks of gestation. Right:major axes 10.6 mm, minor axes 6.5 mm. Left: major axes 11.0 mm, minor axes 6.6 mm\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5932486/v1/4a6f3215fae0019159ad269b.png"},{"id":76752743,"identity":"fc95d364-15c8-4f75-9812-187a826fb44f","added_by":"auto","created_at":"2025-02-20 10:17:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":341922,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flow chart.\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5932486/v1/147d175a220bfd364aeed7ed.png"},{"id":76752554,"identity":"df35bfc7-4469-4555-9e36-9ba9173b7707","added_by":"auto","created_at":"2025-02-20 10:09:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":92245,"visible":true,"origin":"","legend":"\u003cp\u003eTesticular cross-sectional area at 27-30 weeks of gestation. (A) Right testicular cross-sectional area. (B) Left testicular cross-sectional area. Closed circle: fetus with descended testis on the contralateral side. Open triangle: fetus with undescended testis on the contralateral side.\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5932486/v1/d2396abe20d9c2565838e7e1.png"},{"id":76752547,"identity":"5021f3b3-fb30-4a9a-afd4-0459195ea993","added_by":"auto","created_at":"2025-02-20 10:09:02","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":131673,"visible":true,"origin":"","legend":"\u003cp\u003eDevelopment of testicular cross-sectional area in fetuses. (A) Right testicular cross-sectional area. (B) Left testicular cross-sectional area. Broken line indicates the mean and 10th, 90th percentiles.\u003c/p\u003e","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-5932486/v1/0813e7f80fb406a2c538da58.png"},{"id":93095918,"identity":"fe3d1c51-4c2f-41b9-9481-b83c0aacfd9f","added_by":"auto","created_at":"2025-10-09 03:32:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2190288,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5932486/v1/9559a3a7-d7d8-4c53-9eb4-5d8c14dabc1b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sonographic assessment of fetal testicular development and descent","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn the first trimester until around 10 weeks, the formation of external genitalia and masculinization is stimulated by androgens induced by hCG (human Chorionic Gonadotropin) with the peak of this process influencing gonadal differentiation and gender identity.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e From the second to the third trimester of gestation, the GnRH (Gonadotropin-releasing hormone) neuronal system becomes functional, leading to genesis of testosterone, which promotes the development of the penis and testes, and the descent of the testes from the abdominal cavity into the scrotum.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Testosterone concentration level initially decreases after birth, however, one-week-old to a-few-months-old infants produce hormone again due to the GnRH neuronal system.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e This results in an increase in the secretion of FSH (Follicle-Stimulating Hormone), LH (Luteinizing Hormone), and sex hormones comparable to that during puberty, which is considered important for the proliferation of Sertoli cells and germ cells, the development of external genitalia, and the future formation of sperm, called mini-puberty.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Penis and testes grow up due to testosterone in this period, too.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e That is to say, deficiency of testosterone cause to micropenis, cryptorchidism and small testes at fetal to mini-puberty period.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThese are good periods to estimate hypothalamus-pituitary-gonadal system before puberty.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Fetal blood sampling is technically challenging, therefore, such as testicular sizes are used to assess the gonadal dysfunction. However, there are no decisive databases of small testes during the fetal to newborn infants.\u003c/p\u003e \u003cp\u003eIn the past reports of testes size, the prepubertal size is 2\u0026ndash;4 ml,\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e and less than 1ml of the testicular volume, it suggests the possibility of disorder of sexual differentiation or androgen synthesis disorders due to hypogonadotropic hypogonadism at any age before puberty. Testicular volume is positively correlated with total testosterone and sperm concentration in infertile men.\u003csup\u003e\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Thus testicular size is considered a clinical marker of hormonal and spermatogenic function, the assessment of testicular size especially from the fetal to the neonatal period is important. Several studies have used ultrasonography to assess testicular development.\u003csup\u003e\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e However, there are few reports on the development of testicular size during the fetal period using ultrasonography. A cross-sectional study reported that the testicular diameter measured using ultrasonography in fetuses between 20 and 40 weeks of gestation showed a significant positive correlation with gestational age.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e In a cross-sectional prospective study, Achiron et al. reported that testicular circumference in 210 fetuses between 14 and 37 weeks of gestation increased with gestational age.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e To the best of our knowledge, no prospective longitudinal study of fetal testicular size using ultrasonography from the fetal to neonatal period has been conducted. Based on our technique for measuring testicular size in newborn infants using ultrasonography,\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e we considered that it is possible to measure the major (mm) and minor (mm) axes of the testes in fetuses accurately and regularly. Furthermore, we hypothesized that a prospective longitudinal study would allow us to examine the association between fetal testicular cross-sectional area and actual testicular volume in newborns. This is the first prospective, longitudinal study of testicular size development and descent from the fetal to neonatal period using ultrasonography.\u003c/p\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eThe differences between the testicular cross-sectional area in fetuses with both testes descent and unilateral descent were analyzed by the Mann\u0026ndash;Whitney U test. Differences in the major axis, minor axis, and cross-sectional area between the right and left testes were also analyzed using the Mann\u0026ndash;Whitney U test. The correlation between the testicular cross-sectional areas at each period was analyzed using Spearman\u0026rsquo;s rank correlation test. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTo assess the reliability of testicular size measurements using ultrasonography, measurements were performed on eight randomly selected fetuses and infants not included in this study prior to the initiation of the study. The intraclass correlation coefficients of length and width were 0.92 and 0.96, respectively, in the right testis of the fetus, and 0.98 and 0.95 in the left testis of the fetus. The interclass correlation coefficients of length and width were 0.97 and 0.96, respectively, in the right testis of the fetus, and 0.98 and 0.86 in the left testis of the fetus. For testicular volume in newborn infants, the intraclass correlation coefficients of length, width, and height were 0.93, 0.91, and 0.76, respectively, in the right testis, and 0.76, 0.86, and 0.77 in the left testis.\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eA flowchart of the longitudinal study is shown in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. We measured the testicular size in fetuses with confirmed testicular descent. In some fetuses, we could not measure the testicular cross-sectional area owing to the fetal position in the uterus. At recruitment, the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) gestational period was 179.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1 days in 186 fetuses. Maternal and paternal ages were 34.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2 (range, 20\u0026ndash;45) and 34.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9 (22\u0026ndash;57) years, respectively. The number of primiparous and multiparous women was 85 and 101, respectively. Before pregnancy, maternal body height, weight, and BMI were 158.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3 cm, 54.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5 kg, and 21.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 kg/m\u003csup\u003e2\u003c/sup\u003e, respectively. The number of women with a smoking habit before pregnancy was five (2.7%), but no one had this habit during pregnancy. The number of women with pregestational and gestational diabetes was 5 (2.7%) and 15 (8.1%), respectively. Nine (5.8%) women received insulin treatment. Pregestational and gestational hypertension were present in 3 (1.6%) and 20 (10.8%) women, respectively.\u003c/p\u003e\n\u003cp\u003eTesticular descent was found earliest at 24w4d (left side) of gestational age. At less than 27 weeks, only 7% of fetuses had both testes descended into the scrotum. At 27\u0026ndash;30 weeks, 80% of fetuses had both testes descended, and 95% had at least one of them descended. Approximately 100% of fetuses had the testes descended from 31 weeks of gestation. At 27\u0026ndash;30 weeks, the testicular cross-sectional area on the contralateral side in fetuses with an undescended testis was significantly smaller than that in fetuses with both the testes descended (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e; p\u0026thinsp;=\u0026thinsp;0.0014 on the right side and p\u0026thinsp;=\u0026thinsp;0.036 on the left side).\u003c/p\u003e\n\u003cp\u003eThe development of the right and left testicular cross-sectional areas based on the gestational age is shown in Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. Each testicular cross-sectional area increased exponentially with gestational age. The mean cross-sectional areas of the right and left testes at each of the five periods (23\u0026ndash;26 weeks, 27\u0026ndash;30 weeks, 31\u0026ndash;34 weeks, \u0026ge;\u0026thinsp;35 weeks, and neonatal period) were as follows: A:14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8 mm\u003csup\u003e2\u003c/sup\u003e /14.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, B:25.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1 mm\u003csup\u003e2\u003c/sup\u003e /26.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, C:38.0\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0 mm\u003csup\u003e2\u003c/sup\u003e /38.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, D:50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3 mm\u003csup\u003e2\u003c/sup\u003e /49.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, E:50.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6 mm\u003csup\u003e2\u003c/sup\u003e /50.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2 mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The cross-sectional area of each testis in fetuses at \u0026ge;\u0026thinsp;35 weeks was very similar to that in newborn infants. No significant differences were observed in the major axis, minor axis, or cross-sectional area between the right and left testes. The correlations between the right and left testicular cross-sectional areas in each fetus were r\u0026thinsp;=\u0026thinsp;0.75, p\u0026thinsp;=\u0026thinsp;0.004 at 23\u0026ndash;26 weeks; r\u0026thinsp;=\u0026thinsp;0.82, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 at 27\u0026ndash;30 weeks; r\u0026thinsp;=\u0026thinsp;0.72, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 at 31\u0026ndash;34 weeks; r\u0026thinsp;=\u0026thinsp;0.78, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 at \u0026ge;\u0026thinsp;35 weeks; and r\u0026thinsp;=\u0026thinsp;0.72, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 in newborn infants. The testicular cross-sectional areas in fetuses at \u0026ge;\u0026thinsp;35 weeks were moderately correlated with these in newborn infants in both the right and left testes (r\u0026thinsp;=\u0026thinsp;0.42, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, and r\u0026thinsp;=\u0026thinsp;0.46, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, respectively), and with the testicular volume in newborn infants in both the right and left testes as well (r\u0026thinsp;=\u0026thinsp;0.47, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, and r\u0026thinsp;=\u0026thinsp;0.44, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01, respectively).\u003c/p\u003e\n\u003cp\u003eAt 27\u0026ndash;30 weeks, 31\u0026ndash;34 weeks, and more than 35 weeks, in which the proportion of testicular descent was \u0026gt;\u0026thinsp;80%, the association between testicular size and maternal background, fetal developmental parameters, and newborn infants\u0026rsquo; parameters was examined (Table 1\u0026ndash;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;2,\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;3).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e. Comparison of parameters according to testicular cross-sectional area at 27\u0026ndash;30 weeks\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRight (115)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLeft (115)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eSmall (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLarge (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmall (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLarge (58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean testicular cross-sectional area (mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e18.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal age, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e33.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.0\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePaternal age, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e34.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight before pregnancy (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e52.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI before pregnancy (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e21.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight at period B (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e58.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI at period B (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e23.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight gain until period B (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncrease in BMI until period B (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEFBW at period B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1379.6\u0026thinsp;\u0026plusmn;\u0026thinsp;177.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1501.0\u0026thinsp;\u0026plusmn;\u0026thinsp;166.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1414.8\u0026thinsp;\u0026plusmn;\u0026thinsp;186.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1464.5\u0026thinsp;\u0026plusmn;\u0026thinsp;167.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal body height\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e157.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e159.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental weight (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e572.8\u0026thinsp;\u0026plusmn;\u0026thinsp;85.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e600.7\u0026thinsp;\u0026plusmn;\u0026thinsp;122.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e566.3\u0026thinsp;\u0026plusmn;\u0026thinsp;88.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e581.9\u0026thinsp;\u0026plusmn;\u0026thinsp;127.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight in newborn infants (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e3131.6\u0026thinsp;\u0026plusmn;\u0026thinsp;297.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3141.7\u0026thinsp;\u0026plusmn;\u0026thinsp;399.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3085.1\u0026thinsp;\u0026plusmn;\u0026thinsp;317.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3108.7\u0026thinsp;\u0026plusmn;\u0026thinsp;442.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength in newborn infants (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProportion of nulliparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e59.6% (34/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.2% (21/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52.6% (30/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.7% (23/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e10.5% (6/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.9% (4/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.3% (3/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.9% (4/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e7.0% (4/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.6% (5/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.0% (4/57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.9% (4/58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003eBMI: body mass index, EFBW: estimated fetal body weight\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003eDM: diabetes mellitus (prediabetes, gestational diabetes, and/or insulin treatment)\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003eHT: hypertension including hypertension before pregnancy or preeclampsia\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.\u003c/strong\u003e Comparison of parameters according to testicular cross-sectional area at 31\u0026ndash;34 weeks\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"7\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRight (129)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLeft (128)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmall (65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLarge (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmall (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLarge (64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean testicular cross-sectional area (mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal age, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePaternal age, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight before pregnancy (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI before pregnancy (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight at period C (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI at period C (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight gain until period C (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncrease in BMI until period C (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEFBW at period C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2658.9\u0026thinsp;\u0026plusmn;\u0026thinsp;444.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2774.5\u0026thinsp;\u0026plusmn;\u0026thinsp;296.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2699.1\u0026thinsp;\u0026plusmn;\u0026thinsp;291.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2181.0\u0026thinsp;\u0026plusmn;\u0026thinsp;289.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.035\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal body height\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e157.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental weight (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e563.0\u0026thinsp;\u0026plusmn;\u0026thinsp;102.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e594.0\u0026thinsp;\u0026plusmn;\u0026thinsp;104.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e567.1\u0026thinsp;\u0026plusmn;\u0026thinsp;100.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e593.3\u0026thinsp;\u0026plusmn;\u0026thinsp;100.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight in newborn infants (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3081.2\u0026thinsp;\u0026plusmn;\u0026thinsp;350.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3213.7\u0026thinsp;\u0026plusmn;\u0026thinsp;340.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3105.2\u0026thinsp;\u0026plusmn;\u0026thinsp;358.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3168.2\u0026thinsp;\u0026plusmn;\u0026thinsp;359.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength in newborn infants (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProportion of nulliparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.4% (28/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.4% (28/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.4% (28/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.6% (26/64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.6 % (7/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0% (2/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.9% (5/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1% (2/64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5 % (3/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.1% (6/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8% (3/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.3% (4/64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eBMI: body mass index, EFBW: estimated fetal body weight\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eDM: diabetes mellitus (prediabetes, gestational diabetes, and/or insulin treatment)\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eHT: hypertension including hypertension before pregnancy or preeclampsia\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e\u003cstrong\u003e3.\u003c/strong\u003e Comparison of parameters according to testicular cross-sectional area more than 35 weeks\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"7\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRight (132)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLeft (126)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmall (66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLarge (66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep\u003c/p\u003e\n \u003cp\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmall (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLarge (63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean testicular cross-sectional area (mm\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.9\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal age, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePaternal age, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight before pregnancy (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.7\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI before pregnancy (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight at period D (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.8\u0026thinsp;\u0026plusmn;\u0026thinsp;8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI at period D (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWeight gain until period D (kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncrease in BMI until period D (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEFBW at period D\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2658.9\u0026thinsp;\u0026plusmn;\u0026thinsp;444.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2774.5\u0026thinsp;\u0026plusmn;\u0026thinsp;296.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2699.1\u0026thinsp;\u0026plusmn;\u0026thinsp;291.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2715.5\u0026thinsp;\u0026plusmn;\u0026thinsp;458.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal body height\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e157.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental weight (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e563.0\u0026thinsp;\u0026plusmn;\u0026thinsp;102.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e594.0\u0026thinsp;\u0026plusmn;\u0026thinsp;104.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e567.1\u0026thinsp;\u0026plusmn;\u0026thinsp;100.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e590.4\u0026thinsp;\u0026plusmn;\u0026thinsp;104.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody weight in newborn infants (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3081.2\u0026thinsp;\u0026plusmn;\u0026thinsp;350.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3213.7\u0026thinsp;\u0026plusmn;\u0026thinsp;340.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3105.2\u0026thinsp;\u0026plusmn;\u0026thinsp;358.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3210.9\u0026thinsp;\u0026plusmn;\u0026thinsp;324.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLength in newborn infants (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProportion of nulliparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.4% (28/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.4% (28/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.4% (28/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.1% (24/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.6% (7/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0% (2/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.9% (5/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8% (3/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5% (3/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.1% (6/66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8% (3/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.9% (5/63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eBMI: body mass index, EFBW: estimated fetal body weight\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eDM: diabetes mellitus (prediabetes, gestational diabetes, and/or insulin treatment)\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eHT: hypertension including hypertension before pregnancy or preeclampsia\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAt 27\u0026ndash;30 weeks, the right testicular cross-sectional area was significantly correlated with the maternal body weight (p\u0026thinsp;=\u0026thinsp;0.007) and BMI (p\u0026thinsp;=\u0026thinsp;0.021) and with the pre-pregnant maternal body weight (p\u0026thinsp;=\u0026thinsp;0.017). However, these differences were not significant at \u0026gt;\u0026thinsp;31 weeks of gestation (Table 1\u0026ndash;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). At 27\u0026ndash;30 weeks and 31\u0026ndash;34 weeks, the testicular cross-sectional area and EFBW were positively correlated (Table 1\u0026ndash;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;2). At 27\u0026ndash;30 weeks, the right testicular cross-sectional area and parity were significantly correlated (Table 1\u0026ndash;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). More than 35 weeks, the right fetal testicular cross-sectional area was significantly correlated with the body weight and length in infants (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;3). The proportion of mothers with diabetes (moderate and severe gestational or pre-gestational diabetes) and HDP was not associated with fetal testicular size at any time point.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis is the first prospective longitudinal study on testicular size from fetuses to newborn infants in Japan using ultrasonography. We clarified that intra-class and inter-class correlation coefficients in testicular sizes were \u0026gt;\u0026thinsp;0.7 in fetuses and newborn infants. We believe that measurements of testicular size using ultrasonography have high reliability. In a previous study on fetuses, Rotondi et al. reported that the intraobserver repeatability of the measurements was 9.6%,\u003csup\u003e14\u003c/sup\u003e and Achiron et al. reported that intraobserver repeatability, as determined by the coefficient of variation, was 10%.\u003csup\u003e15\u003c/sup\u003e In newborn infants, intra-class correlation coefficients\u0026thinsp;\u0026gt;\u0026thinsp;0.80 with a minimum of 0.57 are reported.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Ultrasonography is a useful tool for measuring fetal and infantile testicular size.\u003c/p\u003e \u003cp\u003eIn this study, the fetal testicular major axis and minor axis were measured using ultrasonography with liner transducers because they are more accurate than the convex transducers normally used for fetal ultrasound. Since no linear probe is currently capable of 3D measurements, we estimated the testicular cross-sectional areas by measuring two dimensions and indicated a testicular developmental curve of cross-sectional area with gestation. The testicular cross-sectional areas in fetuses at 35 weeks of gestation were similar to those in infants. In addition, the fetal testicular cross-sectional area at \u0026ge;\u0026thinsp;35 weeks of gestation was correlated with the neonatal testicular volume. Based on these findings, we believe that fetal testicular cross-sectional area can be measured accurately and reliably, and it can be an indicator of the sex hormone environment in utero as well as testicular volume. However, if the resolution of the convex probe for 3D probing is improved in the future, it may be possible to measure the volume of the testis.\u003c/p\u003e \u003cp\u003eThe study showed that the earliest testicular descent occurred at 24w4d gestation and confirmed that 80% of fetuses have both testes descended into the scrotum between 27 and 30 weeks of gestation, and approximately 100% of fetuses have the testes descended from 31 weeks of gestation in Japan. This result is consistent with those of previous studies. By ultrasonography, Birnholz showed that 62% of fetuses have the testes descended into the scrotum between 28 and 30 weeks, and 93% after 32 weeks.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Malas et al. reported that no testes descended into the scrotum until 27 weeks of gestation and that both testes in all fetuses aged 33\u0026ndash;40 weeks descended into the scrotum.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Rotondi et al. reported that the earliest observation of a descended testis was found in 6.6% at 23 weeks of gestation, and in 98.2% of the fetuses, beyond 32 weeks\u0026rsquo; gestation, both testes had descended in the scrotum.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Achiron et al. reported that no testes were observed in the scrotum before 25 weeks of gestation, 30% had at least one descended testis at 25 weeks, and bilateral testicular descent was observed in 97% of the cases from 32 weeks onwards.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eWe found that the testicular cross-sectional area was smaller in fetuses with unilaterally descended testes than in those with bilaterally descended testes shortly after the testes descended (27\u0026ndash;30 weeks). There are no reports of small testicular size in fetuses with unilaterally descended testes. Physiological testicular descent is regulated by the insulin-like peptide 3 (INSL3) and testosterone. INSL3 plays a role in gubernaculum thickening and retains the testes in the inguinal region. Subsequently, the passage of the testes through the inguinal canal and into the scrotum is largely under androgen control.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e INSL3 was significantly decreased in the non-palpable testes group compared with the palpable testes group in a previous study.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e INSL3 and testosterone levels related to testicular descent might be involved in the small testicular size of unilaterally descended testes. In addition to this, it could be considered about spatial pressure in the inguinal canal versus the scrotum.\u003c/p\u003e \u003cp\u003eThe developmental speeds of various organs during the fetal period are not uniform, and the fetal growth curve differs according to body organs. In a multicenter population-based project, it was reported that the fetal skeleton and abdomen have different velocity growth patterns during intrauterine life.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Rotondi et al. reported a linear relationship between testicular diameter and gestational age between 20 and 40 weeks of gestation.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Achiron et al. reported an exponential relationship between scrotal circumference and gestational age at 14\u0026ndash;37 weeks of gestation.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e In this longitudinal prospective study, we showed that the testicular cross-sectional area exponentially increases with gestational age.\u003c/p\u003e \u003cp\u003eMeasurement of prenatal testicular size and diagnosis of undescended testes during the fetal period are beneficial because they allow for the simultaneous detection of additional complications in fetuses. A small testis may suggest several diseases, such as Klinefelter syndrome, Kallmann syndrome, and Y chromosome microdeletions. Cheng et al. reported that 20% of patients with undescended testes had at least one associated anomaly, such as urogenital disorders, gastrointestinal tract anomalies, abdominal wall defects, or cardiovascular anomalies.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e In addition, we can understand testicular development-related factors in pregnant women by measuring prenatal testicular size. Studies on these factors are also useful for detecting reproductive function after birth. The relationship between maternal smoking and small testicular size in adulthood has been reported.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e Tartarin et al. found that exposure to metformin during intrauterine life reduced the testicular size in fetuses and neoanates.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e In the present study, no women currently smoked or used metformin. It has been suggested that women with preeclampsia had lower levels of estrogen and estrogen receptor-α protein and higher levels of testosterone and estrogen receptor-β protein, suggesting their roles in the pathogenesis of preeclampsia.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e Alsnes et al. reported that testicular volume was higher in boys in the preeclampsia group than in preeclampsia-unexposed boys aged 12 years.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e In the present study, we did not find an association between testicular size and the proportion of participants with Hypertensive Disorders of Pregnancy (HDP) .\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, measurement of circulating hormone levels in maternal and cord blood may be needed. INSL3 and testosterone produced by Leydig cells in fetuses are involved in testicular descent and size. In addition, changes in maternal circulating testosterone levels have been observed in pregnant women with smoking habits,\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e HDP.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e Additional research is required to explore the relationship between circulating endocrine hormones and the factors influencing testicular development. A study combining maternal circulating testosterone and ultrasonography may also be useful. Second, several participants dropped out because of difficulties in measuring maternal obesity and fetal position in the uterus. This is a potential confounding variable in data collection as maternal factors may have an impact on testicular size and descent. It is unclear if the participants that dropped out were different in BMI/hypertension/any other factors affecting testicular size compared with the participants that remained in the study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eWe constructed a growth curve of the fetal testicular cross-sectional area using ultrasonography in a prospective longitudinal study. Fetal testicular cross-sectional area can be an indicator of the sex hormone environment in utero as well as testicular volume. We found that the testicular cross-sectional area of the descended testes in fetuses with unilaterally undescended testis was significantly smaller than that in fetuses with both descended testes shortly after the testes descended.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003ePregnant women whose expected date of delivery was between October 2020 and November 2023 were recruited for this prospective longitudinal study. The exclusion criteria were as follows: fetuses with major anomalies; twin fetuses and fetuses with severe fetal growth restriction; and chromosomal abnormalities. We recruited 189 fetuses at 23\u0026ndash;26 weeks of gestation and excluded two fetuses with trisomy 21 and one fetus with agenesis of the corpus callosum; a total of 186 fetuses were followed up in this longitudinal study.\u003c/p\u003e \u003cp\u003eUltrasonography was performed using a Volson E10 (GE Healthcare, Milwaukee, WI, USA) with a 3\u0026ndash;8 MHz linear transducer (9L) for fetuses (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and a Hi VISION Avius (FUJIFILM, Tokyo, Japan) with a 5\u0026ndash;18 MHz linear transducer (EUP-L75) for newborn infants. We assessed the testis descent in the scrotum and measured the major (mm) and minor (mm) axes of the testes in the scrotum in fetuses, as well as the height in newborn infants. Testicular cross-sectional area was calculated using the following formula: length/2 \u0026times; width/2\u0026thinsp;\u0026times;\u0026thinsp;π. Testicular volume in newborn infants was determined using the prolate ellipsoid formula. Bet\u0026uuml;l et al reported that the ellipsoid formulas are reliable in calculating neonatal testicular by ultrasound.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e All the measurements were performed by the same investigator. Interobserver variability was not calculated because only one observer performed the study. This study was approved by the Institutional Review Board of Tokushima University (approval number: 3433/4264). Written and informed consents were obtained from the study participants and parental guardians of the fetuses. All experimental protocols were designed according to the Declaration of Helsinki\u0026rsquo;s ethical principles and performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eThe authors declare no conflicts of interest regarding the publication of this paper.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors received no financial support for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eA.S. and Y.T. wrote the main manuscript text. A.S. and K.T. performed the ultrasound measurements. A.S. performed the statistical analysis. Y.T., K.T., and I.T. contributed to the interpretation of results and provided feedback. M.A., Y.A., and I.T. critically reviewed the manuscript. All authors have approved the manuscript, agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eThe authors appreciate the support and cooperation of the participants of this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRohayem, J. et al. Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement. \u003cem\u003eEndocr. 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The relationship between ultrasonographically measured testicular volumes and cord blood inhibin B concentrations in healthy term male neonates. \u003cem\u003eReprod. Biol. 23\u003c/em\u003e. 100786. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.repbio.2023.100786\u003c/span\u003e\u003cspan address=\"10.1016/j.repbio.2023.100786\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"fetal testicular size, ultrasonography, undescended testis","lastPublishedDoi":"10.21203/rs.3.rs-5932486/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5932486/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e The aim of this report is to describe techniques and to provide basic and available scientific data on the success of testicular size procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e In this prospective longitudinal study, 186 normal fetuses from 23 weeks of gestation were followed up by ultrasonography. We assessed the testis descent in the scrotum and measured the major (mm) and minor (mm) axes of the testes in the scrotum in fetuses, as well as the height in newborn infants. Testicular sizes were compared among five periods (23-26 weeks, 27-30 weeks, 31-34 weeks, ≥35weeks, and neonatal period).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e The testicular cross-sectional area increased exponentially with gestational age. The cross-sectional area of each testis in fetuses at ≥35 weeks was very similar to that in newborn infants. In both the testes, the fetal testicular cross-sectional area at ≥35 weeks was strongly correlated with the neonatal testicular volume. At 27-30 weeks, the testicular cross-sectional areas of the descended testes in fetuses with unilaterally undescended testis were significantly smaller than those in fetuses with both descended testes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e We provide basic data of fetal testis size and useful way to measure testes size available.\u003c/p\u003e","manuscriptTitle":"Sonographic assessment of fetal testicular development and descent","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-20 10:08:54","doi":"10.21203/rs.3.rs-5932486/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"66e72913-743b-4ea6-92dc-f2e67eff2052","owner":[],"postedDate":"February 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":44174116,"name":"Health sciences/Medical research/Outcomes research"},{"id":44174117,"name":"Health sciences/Endocrinology/Endocrine system and metabolic diseases/Gonadal disorders/Hypogonadism"},{"id":44174118,"name":"Health sciences/Urology/Paediatric urology"}],"tags":[],"updatedAt":"2025-10-09T03:23:59+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-20 10:08:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5932486","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5932486","identity":"rs-5932486","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}