**3. Fetal urine production**

134 From Preconception to Postpartum

adversely affects fetal lung development, resulting in pulmonary hypoplasia, which might lead to death from severe respiratory insufficiency (Nicolini et al., 1989). However, numerous factors complicate the ultrasonographic diagnosis of oligohydramnios. They include the lack of a complete and detailed understanding of the physiology of the dynamics of oligohydramnios. For example, in 40%, the oligohydramnios occurs without any high-risk conditions and the current available data support the expectant noninterventional management of these cases complicated by isolated oligohydramnios (Sherer,

Data: Gilbert WM och Brace RA. Amniotic fluid volume and normal flows to and from the amniotic

Fig. 1. The amniotic fluid turnover at term. Half the secreted liquid from the fetal lungs and oro-nasal cavity reaches the amniotic sack and the other half is swallowed. The clearance

Polyhydramnios (increased volume > 2,000 mL) is found in 1-3% (Volante et al., 2004). The underlying cause of excessive amniotic fluid volume is obvious in some clinical conditions in some clinical conditions and in cases of an minor an minor increase in amniotic fluid volume, the perinatal outcome is good. However, maternal kidney disease, diabetes type 2 and fetal conditions, such as chromosomal abnormalities, most commonly trisomy 21, followed by trisomy 18 and trisomy 13, might be causes (Hill et al., 1987). Moreover, polyhydramnios can be the result of oesophageal atresia and defects in the fetal CNS (Barkin

cavity. Semin Perinatol. 1993; 17: 150-157

pathways are denoted in italics.

et al., 1987; Kimble et al., 1998).

2002).

During the filling phase, the increasing volume of the urinary bladder can be observed, documented and assessed by ultrasound scans.

Fig. 2. This figure shows an appropriate longitudinal bladder image. The 2D ultrasound image on the ultrasound screen was documented on a CD and the volume was calculated in a computer.

The Hourly Fetal Urine Production Rate (HFUPR) can be estimated by regression analysis of calculated bladder volumes documented at different time points within one filling phase (Campbell et al., 1973; Fagerquist et al., 2001; Groome et al., 1991; Nicolaides et al., 1990; Rabinowitz et al., 1989; van Otterlo et al., 1977; Wladimiroff and Campbell, 1974), or by the difference between the maximum and minimum volumes divided by the time interval (Deutinger et al., 1987; Shin et al., 1987; Takeuchi et al., 1994).

Renal Function and Urine Production in the Compromised Fetus 137

When comparing Intra-Uterine Growth-Restricted (IUGR) fetuses with Appropriate weight for Gestational Age (AGA) fetuses at the same gestational age, the HFUPR was significantly lower for IUGR fetuses (Nicolaides et al., 1990; Takeuchi et al., 1994; van Otterlo et al., 1977; Wladimiroff and Campbell, 1974). However, there were no significant differences when the IUGR fetuses were compared with controls of corresponding body weights but with lower gestational ages (Wladimiroff and Campbell, 1974). It was assumed that the reduced urine production rate for IUGR fetuses reflected renal hypoplasia, due to growth retardation. Although different investigations have presented various normal values, the HFUPR in IUGR fetuses compared with fetuses of normal size (AGA) has generally been reported to be lower (Nicolaides et al., 1990; Takeuchi et al.,

In a human 2D ultrasound study comprising IUGR and AGA fetuses, the volume of fetal kidneys, as well as the urine production rate, was estimated (Deutinger et al., 1987). In IUGR fetuses, both the volume of the kidneys and the HFUPR were significantly reduced when compared with the AGA fetuses. In agreement with this study, the growth of fetal kidneys was significantly slower in Small for Gestational Age (SGA) vs. AGA fetuses when it came to the anterio-posterior diameter and transverse circumference of the kidneys (Konje et al.,

The fetal kidneys gradually increase in volume with gestational age (Hansmann, 1985). Renal weight as an autopsy finding is, however, often compromised and associated with a coefficient of variation as large as 50%, due to oedema and passive venous engorgement. Renal functional capacity depends on the number of nephrons, but no known relationship exists between renal weight and the number of glomeruli (Hinchliffe et al., 1991). For many years, estimates of glomerular numbers have therefore been derived using a variety of methods (Bendtsen and Nyengaard, 1989). Unfortunately, these methods have been shown to have some degrees of bias. However, a new stereological dissector technique permits the direct, unbiased estimation of glomerular numbers (Hinchliffe et al., 1992). This new dissector method was used to estimate the number of nephrons in fetuses. The number was 15,000 per kidney in human fetuses at 15 gestational weeks and between 740,000 and

The total number of nephrons was estimated in a comparative investigation of six IUGR stillbirths of known gestational age with controls comprising eleven stillbirths with a birth weight greater than the 10th percentile (prenatal period) and eight liveborn IUGR infants, who died within a year of birth, with a control group of seven appropriately grown infants who also died within a year of birth (postnatal period). The number of nephrons for five of the six IUGR stillborn children and all the growth-retarded children who died within one year was significantly reduced compared with the controls (Hinchliffe et al., 1992). Moreover, in animal models, growth restriction has been associated with a reduced number of nephrons (Bauer et al., 2002; Bauer et al., 2003). It has been suggested that the mechanism underlying the reduced number of nephrons in IUGR fetuses is increased apoptosis due to

stillbirths

**3.1 Urine production in the intra-uterine growth-restricted fetus** 

1997). This divergence was most marked after 26 weeks of gestation.

changes in the levels of apoptosis-related proteins (Pham et al., 2003).

1994; van Otterlo et al., 1977).

**4. Fetal kidneys** 

1,060,000 at term.

Fig. 3. The Hourly Fetal Urine Production Rate (HFUPR) estimation was based on the increase in bladder volume during a filling phase and extrapolated to a time span of one hour.

The filling and emptying dynamics of the fetal urinary bladder have been investigated in detail. The mean time for the bladder-filling phase was 25 minutes (range 7-43 minutes) and it was not significantly influenced by gestational age (Rabinowitz et al., 1989).


(Rabinowitz R, Peters MT, Vyas S, Campbell S, Nicolaides KH. Measurement of fetal urine production in normal pregnancy by real-time ultrasonography. Am J Obstet Gynecol 1989;161(5):1264-6)

Table 1. The maximum bladder volumes before emptying and HFUPR at different gestational ages were calculated by the author according to formulas in the reference article.

#### **3.1 Urine production in the intra-uterine growth-restricted fetus**

When comparing Intra-Uterine Growth-Restricted (IUGR) fetuses with Appropriate weight for Gestational Age (AGA) fetuses at the same gestational age, the HFUPR was significantly lower for IUGR fetuses (Nicolaides et al., 1990; Takeuchi et al., 1994; van Otterlo et al., 1977; Wladimiroff and Campbell, 1974). However, there were no significant differences when the IUGR fetuses were compared with controls of corresponding body weights but with lower gestational ages (Wladimiroff and Campbell, 1974). It was assumed that the reduced urine production rate for IUGR fetuses reflected renal hypoplasia, due to growth retardation. Although different investigations have presented various normal values, the HFUPR in IUGR fetuses compared with fetuses of normal size (AGA) has generally been reported to be lower (Nicolaides et al., 1990; Takeuchi et al., 1994; van Otterlo et al., 1977). 
