Acta Pædiatrica ISSN 0803-5253

REGULAR ARTICLE

Free voiding patterns in preterm and full-term newborn infants are different between males and females Jian Guo Wen ([email protected])1, Chuan Chuan Ren1, Yan Chen1, Yu Tao Lu1, Li Yang1, Lin Gang Cui1, Lu Wen1, Liang Hua Jia1, Yun Long Li1, Qian Zhang2 1.Paediatric Urodynamic Center and Department of Urology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China 2.Department of Neonatal Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Keywords Bladder development, Bladder emptying, Gender differences, Newborn, Voiding pattern Correspondence Jian Guo Wen, Paediatric Urodynamic Center and Department of Urology, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road, No.1, Zhengzhou City 450052, Henan province, China. Tel: +86-18638166007 | Fax: +86-371-66970906 | Email: [email protected] Received 2 March 2014; revised 25 April 2014; accepted 4 June 2014. DOI:10.1111/apa.12714

ABSTRACT Aim: The neonatal period is critical in bladder development, encompassing the transition from foetal bladder contractions to voluntary infant urination. The aim of this study was to investigate different voiding parameters between male and female newborn infants. Methods: We studied 102 healthy, single birth newborn infants – 54 preterm and 48 fullterm – without lower urinary tract diseases, hospitalised in the neonatal intensive care unit from March 2011 to March 2012. Free voiding was observed from 9 a.m. to 9 p.m., and the free voiding parameters and fluid intake were recorded and compared between male and female newborn infants using the Student’s t-test and chi-square test. Results: Male preterm newborns demonstrated larger mean postvoid residual volumes and lower bladder emptying rates than female preterm newborns (p < 0.05), and male full-term newborns had lower bladder emptying rates than female full-term newborns (p < 0.05). The bladder emptying rates of newborns defecating simultaneously with voiding were not statistically different between males and females of the same gestational age (p > 0.05). Conclusion: Male newborns were more likely to have larger postvoid residual volumes than females, and defecating simultaneously with voiding may promote bladder emptying in male newborns.

INTRODUCTION In the past few years, voiding function in infants has attracted the attention of many paediatric researchers, and significant insights have been obtained into the normal and dysfunctional voiding mechanisms in newborns (1,2). The neonatal period is critical in bladder development, as it encompasses the transition from the foetal bladder contraction phase to voluntary infant urination. It remains difficult to recognise abnormal voiding in diaper-wearing infants even when extreme symptoms, such as straining, are observed. Symptoms suggesting the need for treatment also differ in infants and toilet-trained children. In addition, the diagnostic tools are limited, and it is difficult to obtain more than sporadic measurements of urine flow and residual urine. In adults, the maximum bladder capacity and voiding frequency are different between males and females (3,4). However, few studies have evaluated these differences in newborns (5). Therefore, the aim of the present study was to explore the normal development of free voiding patterns in newborns and investigate the difference in free voiding parameters between male and female newborns.

First Affiliated Hospital of Zhengzhou University in China. Of the 48 full-term newborns, 30 were males (gestational age 39.2  0.9 weeks with a range of 37–40 weeks, birth weight 3.2  0.3 kg, age 4.2  1.6 days) and 18 were females (gestational age 39.5  0.8 weeks, with a range of 37– 40 weeks, birth weight 3.4  0.4 kg, age 4.3  1.4 days). Of the 54 preterm newborns, 26 were males (gestational age 34.2  1.8 weeks, with a range of 30–36 weeks, birth weight 2.2  0.5 kg, age 3.5  1.8 days) and 28 were females (gestational age 34.4  1.3 weeks, with a range of 30– 36 weeks, birth weight 2.4  0.4 kg, age 3.3  2.1 days).

Key notes 



 METHODS We included 48 healthy full-term and 54 healthy preterm newborns, aged from 3 to 7 days, who were admitted to the

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The neonatal period is critical in bladder development, encompassing the transition from foetal bladder contractions to voluntary infant urination. We carried out a 12-h observation of free voiding patterns in 102 healthy, single birth newborns to investigate different voiding parameters between males and females. Male newborns were more likely to have larger postvoid residual volumes than females, and defecating simultaneously with voiding may promote bladder emptying in male newborns.

©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. e450–e453

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The gestational age, age and body weight were matched between male and female newborns in each group, with no significant statistical differences. All newborns underwent urinary ultrasound prenatally and post-natally. Newborns with any signs of urinary tract pathology or symptoms were excluded. All Apgar scores were above eight at 1-min and 5-min assessments. The study protocol was approved by the regional ethics committee and was performed in accordance with the Declaration of Helsinki. Informed consent was obtained before the study from the parents of all the newborns. All newborns were observed for 12 h by experienced urologists in accordance with International Children’s Continence Society (ICCS) standards (6). The subjects were observed from 9 a.m. to 9 p.m. on day 3 to 7. For the newborns, breastfeeding began 6 to 12 h after birth, and some quantity of water was provided in the interval, according to the standard protocol (7). The voiding interval time (VIT), voiding volume (VV), postvoid residual volume (PRV), bladder emptying rate (BER) and occurrence of defecation simultaneously with voiding (DSV) were recorded. Voiding volume was defined as the difference in diaper weight, weighed using a PL602-S balance (accuracy 0.1 g; Mettler Toledo, Greifensee, Switzerland) before and after voiding. If there were stools on the diaper, we got rid of them first and then weighed the diaper. The PRV was measured within 30 sec of voiding using ultrasound (GE, Inc., LOGIQ400, Milwaukee, WI, USA). Every PRV was measured three times, and the mean value was defined as the PRV volume. Maximum cross section measured diameter (d1), thick diameter (d2) and midline longitudinal section diameter (d3) of the echo-free zone of the bladder after voiding was recorded, and the ellipsoid formula was used to calculate the residual urine volume (V = 1/2 9 d1 9 d2 9 d3). BER was defined as the total number of voids without PRV divided by the total number of voids. The bladder capacity (BC) was defined as VV plus the PRV measured immediately after voiding. The maximum value for any one newborn was accepted as the individual’s BC. Statistical analyses were performed using Statistical Package for Social Sciences, version 10.0 for Windows (SPSS, Inc., Chicago, IL, USA). Variables were expressed as mean  standard deviation. Student’s t-test and chi-square test were used to determine the difference between the two groups. p values 0.05) (Tables S1 and S2). The influence of defecation on voiding parameters Forty episodes of defecation occurring with micturition were recorded in preterm newborns (16 male and 24 female), and 43 episodes were recorded in full-term newborns (32 male and 11 female). Overall, 12.4% (83/668) of the voids occurred with defecation. There was no statistically significant difference in BER in the male newborns when defecation occurred simultaneously with voiding compared with female newborns of the same gestational age (preterm, 25% vs. 41.7%; full-term, 28.1% vs. 36.4%; p > 0.05) (Tables S1 and S2).

DISCUSSION Few studies have investigated urine storage and micturition functions in children’s bladders (8). Urodynamic tests are an invasive examination, which would be inappropriate in healthy newborns. It is much more suitable to use observational methods to study the bladder function in newborns. In prior studies, we have established the normal free voiding parameters of healthy newborns (9). This study looked at the difference in free voiding parameters between male and female newborns, to develop further understanding of the bladder function in newborns. The differences of VV, BC and VIT between male and female newborns As bladder function is immature in newborns, the VV varies greatly. In our study, the mean VV was 6.7 mL (range 3.5– 11.2 mL) and 34 mL (range 20–64 mL) for preterm and full-term newborns, respectively (10,11). In an observational study of 11 male and eight female preterm newborns, Sill en et al. (10) reported that the VV of female preterm newborns was slightly less than that of male preterm newborns. However, this was not a significant difference. In our free voiding study, the VV of female preterm newborns was slightly higher than that of male preterm newborns (12.8 mL vs. 11.2 mL), although this difference was not significant. In the study by Sill en, the gestational age of newborns was not considered, whereas in our study, we closely matched the gestational age and post-natal age of both female and male preterm newborns (Table S3). So, we believe our study more accurately reflects the VV of female and male preterm newborns. Our results also showed that VV was not significantly different between female and male

©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. e450–e453

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full-term newborns (21.8 mL vs. 21.2 mL) and was less than in the study of 6.5-month-old full-term newborns, previously reported by Holmdahl et al. (11) (Table S3). The increase in BC is not linearly related to age or weight during the first year of life (12). In previous free voiding studies, the median BC was 12 mL for preterm newborns born at week 32 of gestation and 52 mL for full-term newborns aged 3 months (10,13). In our study, the results showed that the mean BC was 22.2 mL for preterm newborns born at week 33 of gestation and 35.7 mL for full-term newborns born at week 39 of gestation (Table S1). Our results are consistent with the previously reported results (Table S3). Sillen et al. (10) reported that in preterm newborns, the BC of males was greater than that of females. According to Holmdahl et al. (11), the BC of full-term females of up to 6 months of age was greater than that of males, but after 6 months of age, the males had a greater BC. However, our results showed that there was no significant difference in BC between males and females, both in preterm and in full-term newborns. This is quite different from the findings in adults showing that the BC of women is less than that of men (4). Few studies have evaluated the influences of androgens on BC in animals and humans, and the results have been contradictory. Nicholson et al. (14) reported that mice treated with 25 mg testosterone and 2.5 mg 17b-estradiol for 2 or 4 months developed significantly larger bladders than untreated mice. In contrast, Celayir et al. (15) reported that androgens could reduce the BC of female intersex patients. The bladder develops simultaneously in both sexes, beginning from the urogenital sinus and gradually into a cystic urine storage organ. Therefore, no significant difference exists in BC in newborns, as the results of our study show. However, BC changes under the effects of different sex hormones as well as different length of urethra and the surrounding structures. With growth and development into adulthood, the difference in BC between males and females begins to appear. Further studies are needed to better delineate the sequence of events affecting BC. The VIT is closely related to BC and urine production. Urine production decreases with age in terms of mL/kg per h but increases in total amount. Sillen (12) reported that the urine production in preterm infants (gestational age: 32 weeks) was 6 mL/kg per h, but 5 mL/kg per h in fullterm infants. In agreement with previous studies, our results show that there is no significant difference in VIT between males and females in either preterm or full-term newborns. As the BC is larger and urine production is slower for fullterm newborns, the VIT of full-term newborns should be longer than that of preterm newborns. However, our results showed that full-term newborns’ VIT is shorter than the preterm newborns’ VIT. This may be because the renal function of full-term newborns is more mature than that of preterm newborns, and total fluid intake is higher in fullterm newborns that are fed regularly day and night. This leads to higher urine production in full-term newborns and subsequently a shorter VIT than that seen in preterm newborns.

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Differences in PRV and BER between male and female newborns Detrusor–sphincter dis-coordination is a normal part of the voiding pattern in newborns and may cause incomplete emptying and PRV (16). Duong et al. (17) reported that PRV decreased with age and that by the age of 9 months, bladder emptying in children is regarded as complete. According to the study by Sill en et al., the PRV of females was less than that of males in preterm newborns, while it was greater in full-term female newborns than in full-term male newborns, although none of these showed a significant difference. Our results showed that the PRV of preterm male newborns was greater than that of preterm female newborns (1.9 mL vs. 0.9 mL) and that this difference was statistically significant. However, the difference in full-term newborns was not significant (1.6 mL vs. 1.1 mL) (Table S1). This may indicate that the bladder function of male full-term newborns is more mature than that of male preterm newborns. Although newborns do not empty the bladder at every void, according to Nev eus & Sill en (16) one void in 4 h is complete. Because the length of the urethra and the surrounding structures are different between males and females, men need higher detrusor pressure to void (18). Therefore, we speculated that these factors may cause lower BER in male newborns than female newborns. Our results confirmed the theory that BERs of preterm and full-term male newborns were all lower than those of female newborns of the same gestational age (7.7% vs. 42%; 15.8% vs. 44.5%) (Table S1). The total BERs of male and female newborns were 12.4% (47/378) and 43.1% (125/ 290), respectively (Table S2). Although the BER of male newborns was lower than that reported in previous studies, the total BER of male and female newborns (25.7%, 172/ 668) was consistent with these reports (Table S1). Influence of defecation on voiding With the complex innervations of the pelvic floor, voiding dysfunction is usually accompanied by abnormal defecation (19). However, the relationship between voiding and defecation, and whether defecation affects voiding, is still unknown. It has been assumed that during defecation, abdominal pressure increases and the muscles of pelvic floor relax and that these could promote bladder emptying. Gladh et al. (20) reported that 14% of voids occurred together with defecation. Our results showed that 12.4% (83/668) of voids occurred with defecation and, when defecating, the BERs of male and female newborns were all increased. When defecation occurred simultaneously with voiding, the BERs of preterm and full-term male newborns were 25% and 28.1% and did not differ significantly from those of female newborns at the same gestational age (41.7% and 36.4%) (Table S1). Once again, these findings may be due to the structural differences in the pelvic floor and lower urinary tract between males and females. Defecation may induce more relax of pelvic floor and higher abdominal pressure than that of normal voiding in males, and this may contribute to improved bladder emptying.

©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2014 103, pp. e450–e453

Wen et al.

However, the shorter female’s urethra and different surrounding structures only require a very low detrusor pressure to accomplish micturition. Therefore, defecation has more significant impact on voiding for male newborns than for female newborns and promotes bladder emptying. From our observational study, we conclude that female newborns find it easier to empty their bladder, whereas male newborns are more likely to have PRV. DSV may promote bladder emptying in male newborns. The sequential changes in bladder function that occur between the neonatal stage and adulthood need future investigation.

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Free voiding patterns in preterm and full-term newborn infants are different between males and females.

The neonatal period is critical in bladder development, encompassing the transition from foetal bladder contractions to voluntary infant urination. Th...
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