Fetal brain to liver weight ratio as a measure of intrauterine growth retardation: analysis of 182 stillborn autopsies.

The fetal brain/liver weight ratio of 182 stillborn fetuses was analyzed for its value as a measure of intrauterine growth retardation. The ratio was evaluated as a test for the detection of small-for-gestational age fetuses, compared with the ponderal index, and evaluated for correlation with maternal histories that were compatible with fetal growth retardation. Both brain/liver ratio and ponderal index were insensitive and relatively nonspecific indicators of low fetal body weight in this population. Brain/liver weight ratio was considerably more sensitive in those cases that were at least 20 weeks of gestational age, and specificity increased as the cut-off point was increased above 3. Those cases with maternal history or placental findings compatible with asymmetrical-type intrauterine growth retardation were statistically more likely to have elevated brain/liver weight ratios and depressed ponderal indices, but there was considerable overlap among cases with different disease types. Prosectors of fetal autopsies must make use of all the information available to them. The fetal brain/liver weight ratio and the ponderal index may be useful, but they are not satisfactory indicators of intrauterine growth retardation by themselves, and they also may be inadequate for the detection of growth retardation etiology.     

Timing is everything: A reconsideration of fetal growth velocity patterns identifies the importance of individual and sex differences

Fetal growth has been posited to follow a “timing hypothesis” sequence in which the second trimester favors a single growth velocity peak in body length and the third trimester accommodates a single growth velocity peak in weight accrual. To our knowledge, this proposition has never been tested with high‐frequency longitudinal ultrasound data from normally growing human fetuses. The present study examined whether fetal growth in leg length had its peak velocity at or about 20–26 gestational weeks and declined subsequently and whether estimated fetal weight velocity was maximal at or about 33 weeks and declined subsequently; if the greatest acquisition of leg length occurred in the second trimester and weight in the third trimester; and if birth outcomes reflected these relationships. The data in this study included approximately weekly longitudinal ultrasound data collected from 44 maternal/fetal pairs in Brussels, Belgium. Diaphyseal lengths of the femur and tibia provided information on leg growth and estimated fetal weight was assessed from the biparietal and occipital‐frontal head diameters and transverse and anterior–posterior diameters of the abdomen. Growth patterns were investigated from individual growth curves derived from daily growth velocity z‐scores. Paired t‐tests compared individuals' trimestral increments in leg length and fetal weight. Least‐squares regression models employing the robust procedure for repeated measurements were used to test for relationships between trimester, size, growth rates, and birth outcome, controlling for day of measurement, sex, maternal smoking, and gestational age at birth. The normal fetuses in this study grew by pulsatile patterns of leg and estimated weight acquisition, not a single peak and decline process. Greater incremental growth in estimated fetal weight occurred during the second trimester and leg length in the third trimester. Individual and sex effects were significant in growth velocity patterns. Girls grew with greater synchrony between leg and weight growth and were accelerated by comparison with boys, with faster leg growth predicting lower ponderal index by the second trimester. Birth outcomes were sex‐specific in timing effects and predictive variables. These results support the importance of sex‐specific analyses, reemphasize the common notion that girls grow faster than boys, and direct attention to cross‐talk between energy resources and growth. Am. J. Hum. Biol. 15:667–680, 2003. © 2003 Wiley‐Liss, Inc.     

Early rapid growth,early birth: Accelerated fetal growth and spontaneous late preterm birth

The past two decades in the United States have seen a 24% rise in spontaneous late preterm delivery (34–36 weeks) of unknown etiology. This study tested the hypothesis that fetal growth was identical prior to spontaneous preterm (n = 221, median gestational age at birth 35.6 weeks) and term (n = 3706) birth among pregnancies followed longitudinally in Santiago, Chile. The hypothesis was not supported: Preterm‐delivered fetuses were significantly larger than their term‐delivered peers by mid‐second trimester in estimated fetal weight, head, limb, and abdominal dimensions, and they followed different growth trajectories. Piecewise regression assessed time‐specific differences in growth rates at 4‐week intervals from 16 weeks. Estimated fetal weight and abdominal circumference growth rates slowed at 20 weeks among the preterm‐delivered, only to match and/or exceed their term‐delivered peers at 24–28 weeks. After an abrupt growth rate decline at 28 weeks, fetuses delivered preterm did so at greater population‐specific sex and age‐adjusted birth weight percentiles than their peers from uncomplicated pregnancies (P < 0.01). Growth rates predicted birth timing: one standard score of estimated fetal weight increased the odds ratio for late preterm birth from 2.8 prior to 23 weeks, to 3.6 (95% confidence interval, 1.82–7.11, P < 0.05) between 23 and 27 weeks. After 27 weeks, increasing size was protective (OR: 0.56, 95% confidence interval, 0.38–0.82, P = 0.003). These data document, for the first time, a distinctive fetal growth pattern across gestation preceding spontaneous late preterm birth, identify the importance of mid‐gestation for alterations in fetal growth, and add perspective on human fetal biological variability. Am. J. Hum. Biol., 2009. © 2008 Wiley‐Liss, Inc.     

Fetal growth and well-being in a study of maternal hypertension in rabbits

Obtaining growth and physiologic data in the postnatal laboratory animal is common. However, monitoring growth in utero is far more difficult, with little data available except upon termination of pregnancy. High-resolution ultrasound was used to monitor growth, morphology, and fetal well-being in normotensive and hypertensive rabbits (21 fetuses) at day 16, 20, and 26 of the 32 day gestational period. Set protocols, comparable to those routinely assessed in humans, were devised and followed for each examination. Birth weight was greater in offspring of hypertensive as compared to normotensive mothers (p < 0.001); however, litter size was reduced. The greater birth weight was reflected in growth parameters measured throughout gestation indicating the predictive value of ultrasound. High-resolution ultrasound was a reliable and sensitive method for biometric and morphologic assessment of the fetal rabbit, demonstrating that growth trajectory of offspring of hypertensive mothers may be altered early in gestation.     

Growth patterns of the heart and kidney suggest inter-organ collaboration in facultative fetal growth.

Maternal smoking during pregnancy has been associated with a number of negative sequelae among offspring, including elevated postnatal blood pressure. While animal studies have described organ level alterations with smoke exposure, human data have been more limited. Thirty-four healthy maternal/fetal pairs (24 nonsmokers, 10 smokers) participated in a longitudinal growth study from the thirteenth week of pregnancy to document fetal kidney and heart growth trajectories and morphology. Curve fitting followed by a mixed model for repeated measures identified significantly different growth patterns in kidney width, thickness, length, and volume growth with exposure: the smoke-exposed fetal kidney was wide and thick compared to the unexposed kidney during the second and early third trimester, declining to proportionately thin kidneys for length and width subsequently. Cardiac growth in width and volume followed a reverse pattern: a surge in cardiac volume occurred after 30 weeks with acceleration in cardiac width, resulting in a heart that was wide for length and for fetal weight. Smoke exposure altered fetal growth in size and timing of the heart and kidneys during midgestation, with changes in organ morphology suggesting compensatory growth. These are the first data providing anatomical evidence of altered renal/cardiac volume relationships that may provide a mechanism to previously reported sequelae of in utero smoke exposure. They suggest that cell-level adaptive responses to hypoxia and/or chemical insults are operative and illustrate the importance of longitudinal ultrasound to directly assess the organ-level growth response of the human fetus to a prenatal stress, in lieu of relying on birth outcome measures.     

Alcohol delays the emergence of the fetal elicited startle response, but only transiently

Prenatal exposure to alcohol may exert a significant detrimental effect on the functioning of the individual's brain, however few studies have examined this before birth. This longitudinal study examined the effect of maternal alcohol consumption on the elicited startle response of the fetus. Two groups of fetuses were examined: one whose mothers drank alcohol (approximately 10 units per week); the other whose mothers did not drink alcohol. Fetuses were examined at 29, 32 and 35 weeks gestation and their startle response observed using ultrasound in response to 2 presentations of a pink noise (70-250Hz) at 90dB(A) separated by 30s. Fetuses exposed to alcohol exhibited a weaker startle response at 29 weeks gestation than did fetuses not exposed to alcohol. There was no difference in the response at 32 and 35 weeks gestation. To ensure that the effects were not due to a more general effect of alcohol on fetal movement, a second experiment compared the spontaneous movements (observed on ultrasound for 45 min) of fetuses whose mothers drank alcohol and fetuses of mothers who didn't drink alcohol. There were no differences in movements exhibited by the fetuses. The results suggest that exposure to alcohol delays the emergence of the elicited startle response at 29 weeks gestation but this delay has disappeared by 32 weeks gestation. The possible role of altered neural development, acute exposure to alcohol and disruptions to the fetus's behavioural repertoire, in mediating these effects are discussed.     

Apparent normalisation of fetal renal size in autosomal dominant polycystic kidney disease (PKD1)

We present a family with adult onset autosomal dominant polycystic kidney disease (ADPKD) in two generations, linked to the PKD1 locus and with paternal transmission to the fetus. The fetus carried the PKD1 haplotype and was, therefore a gene carrier. Progressive hyperechogenic renal enlargement, but no cysts, was documented by serial fetal ultrasounds at 21, 23 and 34 weeks of gestation. Surprisingly, the newborn renal scan showed normal sized kidneys with apparently normal corticomedullary differentiation. However, at 11 months of age, the evolution of cysts in one kidney, and then in the other kidney at 20 months, was documented by ultrasound in the absence of clinical symptoms or signs. The observed normalisation of fetal renal ultrasound appearances at birth has not previously been described in fetuses presenting with PKD1.     

Fetal size at the 32nd gestational week is associated with the risk of breech presentation at term birth

Objectives

The association patterns between breech presentation at birth and fetal biometry at the first, second, and third trimesters, newborn size but also maternal age, body height, prepregnancy weight status as well as gestational weight gain, were analyzed using a dataset of 4501 singleton term birth in Vienna, Austria.

Methods

In this medical record-based study, fetal biometry was reconstructed based on the results of three ultrasound examinations conducted at the 11th/12th, 20th, and 32nd gestational weeks. Head dimensions, abdominal dimensions, and femur length were determined by sonography. Birth weight, birth length, and head circumference were measured immediately after birth.

Results

The total breech presentation rate at birth was 6.2%. Breech newborns were significantly (p < 0.001) shorter and lighter at the time of birth, their head circumferences, however, were significantly larger (p = 0.001). At the 32nd week, breech fetuses showed significantly smaller biparietal breadths, but highly significantly longer heads. Their abdominal dimensions were significantly smaller, and their femora were shorter. Higher maternal age, and a longer, but narrower fetal head as well as smaller abdominal dimensions at the 32nd gestational week were independently related to a higher risk of breech presentation at the time of birth.

Conclusions

Fetuses who remain in a breech presentation until term birth (≥37 gestational weeks) differed significantly in head and abdominal dimensions from cephalic fetuses from the 32nd gestational week onwards.     

Use of serial ultrasound to identify periods of fetal growth restriction in relation to neonatal anthropometry.

The developmental origins of the health and disease hypothesis suggests that fetal growth restriction (FGR) is a risk factor for several chronic diseases of adulthood. However, most supporting studies use birth weight as a proxy measure of FGR. To examine the relationship between birth weight and FGR, the present study used serial prenatal ultrasound to identify periods of FGR during gestation, and related these periods to birth size and shape. The data in this study included serial prenatal ultrasounds performed on 1,349 high-risk Scandinavian women enrolled in the National Institute of Child Health and Human Development Study of Successive Small for Gestational Age Births. Fetal growth velocity between ultrasounds was used to identify periods of isolated FGR, and these were studied in relation to anthropometry at birth. FGR was identified in 184 subjects. A control group of 384 subjects without FGR was also identified. Infants with first-trimester FGR (n = 20) had the highest birth weight, ponderal index, and subscapular skinfold thickness. Infants with second-trimester FGR (n = 37) had the highest arm fat percentage. Infants with early third-trimester FGR (n = 55) had the lowest mean birth weight and ponderal index. When infant gender, gestational age, maternal body mass index, and smoking were controlled, birth weight was predicted only by third-trimester FGR (not first- or second-trimester FGR), and arm fat percent was predicted only by second-trimester FGR. These results suggest that birth weight is not a valid indicator of FGR occurring before the third trimester. Body composition may be a more sensitive marker of early FGR.     

Relationship between maternal serum vascular endothelial growth factor concentration in early pregnancy and fetal and placental growth.

Vascular endothelial growth factor (VEGF) has important effects on endothelial cells increasing cell proliferation, permeability and nitric oxide production; concentrations of VEGF in the maternal serum increase during the first 10 weeks of pregnancy. In this study, the relationship of maternal serum VEGF with maternal health during pregnancy and with fetal and placental size at mid-pregnancy and at term was investigated. Serum was obtained from 539 Caucasian women with singleton pregnancies between 8 and 20 weeks of pregnancy (mean 14 weeks). Total serum VEGF concentrations were measured by direct competitive radioimmunoassay. Fetal size and placental volume were measured by ultrasound between 16 and 20 weeks gestation. Birthweight, placental weight and anthropometric measurements of the baby were obtained after delivery. Serum VEGF concentrations were found to be higher in women with a lower weight before pregnancy (P = 0.01) and in those carrying a female fetus (P = 0.002). VEGF concentrations were positively correlated with placental volume (r = 0.17, P = 0.0001) but not with fetal size between 16 and 20 weeks gestation. Serum VEGF concentrations were positively correlated with both birthweight (r = 0.10, P = 0.02) and placental weight at delivery (r = 0.13, P = 0.003). The data presented support the view that VEGF may be one of the factors involved in mediating the maternal cardiovascular adaptation to pregnancy.     

Three-dimensional qualitative sonographic evaluation of fetal soft tissue

Even though fetal growth restriction and macrosomia remain as major problems currently facing obstetricians, there is still no modality for the assessment of fetal soft tissue deposition and muscle mass in utero. A total of 52 fetuses from 29 to 41 weeks gestation were studied within 1 week before delivery using a transabdominal three-dimensional (3D) transducer (3.5 MHz). Their birth weights varied from 1016 to 4018 g, and their crown-heel length from 37 to 54 cm. The amount of subcutaneous tissue was estimated using the fetal nutrition score. The fetal nutrition score values were determined from a qualitative assessment of the amount of subcutaneous tissue present at three locations (face, ribs and buttocks) on the antenatal 3D ultrasonograms. Fetal nutritional status, using fetal nutrition score, was compared with that found by modified neonatal nutrition score and ponderal index respectively. There was a significant linear correlation between fetal nutrition score and modified neonatal nutrition score. Fetal or neonatal nutrition score were strongly correlated with birth weight and neonatal crown-heel length. However, no significant correlation was found between ponderal index, fetal nutrition score, or modified neonatal nutrition score. Ponderal index also was not correlated with birth weight and neonatal crown-heel length. Moreover, fetal nutrition score was correlated with Apgar score, but not with umbilical cord arterial blood pH. Therefore, doubt is cast on the usefulness of the ponderal index for measurement of neonatal soft tissue and muscle mass. Fetal nutrition score using 3D ultrasonography provides a novel means of evaluating the nutritional status of the fetus in utero, and should be useful for predicting the extremes in fetal growth (fetal growth restriction and macrosomia) at an earlier stage than hitherto achieved.     

Effects of maternal bilateral ureteral ligation on the development of the proximal tubule of the kidney in fetal rats: morphometry and electron microscopic study

Development of the proximal tubule in the fetal kidney was studied following ligation of both ureters of pregnant rats. The ligation was performed on days 15, 17, 19, and 21 of gestation and autopsy followed 24 hours after each operation. On fetal days 20 and 22, the proximal tubular length per unit volume (1 mm3) of whole kidney of the fetuses from the ligated mothers was significantly increased, while the ratio of total glomerular volume to total proximal tubular volume was remarkably decreased when compared to that of the fetuses from the non-ligated mothers. Apical vacuoles in proximal tubular cells were increased by the ligation on fetal days 20 and 22. These findings suggest that maternal bilateral ureteral ligation accelerates the growth and differentiation of the proximal tubule in fetal kidney, when the fetal kidney is functional in urine production.     

Cardiac response of the fetal rat to carbon monoxide exposure

Groups of pregnant rats were exposed to 200, 166, and 157 ppm CO for the last 17 out of 22 days of gestation. The number of fetuses per dam or live young per litter were unaffected. Neonatal red blood cell count was depressed, whereas mean corpuscular hemoglobin and volume were elevated. Birth weight was reduced; heart weight, heart weight-to-body weight ratio, placental weight, and placental weight-to-body weight ratio were elevated. Identical results were obtained in studies of fetuses examined daily during the final 4 days of gestation at 200 ppm. Cardiomegaly present at birth was not due to elevated myocardial water content, as dry heart weight and wet heart weight increased proportionately. Heart DNA content (microgram) was increased at both 157 and 200 ppm CO in neonates and fetuses, whereas DNA concentration (microgram/mg dry wt) was similar to the controls. Cardiac hydroxyproline concentration (microgram/mg dry wt) and content (microgram) were unaffected in neonates by fetal CO exposure at 157 and 200 ppm, although the hydroxyproline content was elevated in fetuses at 157 ppm CO. Cardiac lactate dehydrogenase (LDH) M subunit composition was elevated from 4 days before birth, until birth, at 200 ppm CO, whereas total LDH activity was unchanged. Although neonatal myocardial cytochrome c was unaltered by fetal CO exposure, myoglobin concentration (mg/g) and content (mg) were elevated. Prolonged maternal CO inhalation thus exerts significant effects on fetal body and placental weight, heart weight, enzyme constituents, and composition.     

Fetal programming of temperamental negative affectivity among children born healthy at term

The fetal programming hypothesis suggests that an adverse in utero environment, reflected in small body size at birth, has life-long effects on different physiological systems that may affect both health and behavior. We explored whether fetal growth was associated with biologically based temperamental outcomes (negative affectivity scales, the CBQ) among 5(1/2)-year-old children (n = 416) born healthy at term (gestational weeks 37-42). In line with the hypotheses, small body size at birth (thinness measured by ponderal index, kg/m(3)) was related to increased negative affectivity and its subscales: anger-, discomfort-, and sadness-proneness in childhood. Longer length at birth was predictive of higher levels of child anger- and sadness-proneness. Length of gestation moderated the associations of weight and length at birth with negative affectivity. The results suggest that the biological basis of temperament may be subjected to antenatal environmental influences, and that the mechanisms, proposed to be related to fetal glucocorticoid environment, may operate even within the normal range of term birth.     

Developmental trajectories of general and breathing movements in fetal twins

This study examined the developmental trajectories of general and breathing movements in fetal twins. Fetal movement patterns were assessed from real-time ultrasound recordings performed at 12-15, 20-23, and 28-32 weeks of gestation in 42 twin pairs. Results indicated that both general movements and breathing movements followed a curvilinear, inverted U-shaped curve. Developmental trajectories were unrelated within pairs of twins and were not associated with gestational age at birth and birth weight. However, sex differences were found for general movements with males displaying more time making general movements at 21 weeks and a steeper decline in time spent making general movements during the second half of pregnancy than females. These age-related changes in fetal movements may reflect CNS development. These findings also suggest that twins’ behavioral development is largely independent of co-twin development, gestational age at birth, and birth weight, but not of fetal sex.     

Fetal biometry in the Brachmann-de Lange syndrome

The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established rations of fetal body proportions. The cross-sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of “small for gestational age” would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length ) in 4 of the 11 fetuses where such information could be obtained. BDLS fetuses demonstrate early and symmetric intrauterine growth retardation. We conclude that fetal biometry can provide a valuable index in the assessment of a pregnancy suspected to be at risk for a severely affected BDLS child. © 1993 Wiley-Liss, Inc.     

Self‐reported illness and birth weight in the Philippines: Implications for hypotheses of adaptive fetal plasticity

It has been proposed that prenatal nutrition provides the fetus with a cue allowing it to adjust biological settings in anticipation of postnatal nutrition. To evaluate the reliability of fetal growth rate as a nutritional cue, this study assesses the extent to which a nonnutritional factor‐maternal illness symptoms during pregnancy‐predicts birth outcomes in a large, population‐based sample of Filipino women and their newborns (n = 2,887). Self‐reported illness symptoms were collected during pregnancy and used to predict weight, length, BMI, and gestational age at birth. Independent of potential confounders, number of reported symptoms predicted a significant dose‐response decrease in birth weight and BMI, but not length that reflected a combination of reduced fetal growth rate and reduced duration of gestation. These effects were comparable in male and female offspring, but tended to be stronger when reported closer to term. Among women interviewed at 32 weeks gestation or later, multiple symptoms predicted a 144 g birth weight reduction compared with no symptoms. These findings suggest an acute effect of maternal illness on fetal nutrition late in gestation when growth rate and fat deposition are most rapid. Although modest, the effect was larger than that of most pregnancy macronutrient supplementation trials. These findings using crosssectional, self‐reported illness symptoms highlight a nonnutritional maternal influence on fetal nutrition, which could attenuate its value as a cue of postnatal ecology. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.     

Clinical application of fetal sex determination using cell-free fetal DNA in pregnant carriers of X-linked genetic disorders

As the first step in prenatal diagnosis of X-linked genetic disorders, chorionic villus sampling (CVS) for fetal sex determination is generally performed at 11-13 weeks of gestation. However, as the procedure-related miscarriage rate of CVS is 0.5-1.0%, non-invasive methods such as PCR of cell-free fetal DNA (cff-DNA) in maternal plasma are preferable. Here, we determined fetal sex at 9-12 weeks of gestation using PCR of cff-DNA in three pregnant carriers of Duchenne muscular dystrophy. The fetal sex was accurately determined in all three cases, as confirmed by ultrasound and amniocentesis at 16 weeks (for the two female fetuses) and CVS at 12 weeks (for the one male fetus). This procedure could avoid unnecessary CVS in female fetuses.     

An exploratory study of fetal behavior at 33 and 36 weeks gestational age in hypertensive women

The relationship between maternal blood pressure (BP) and fetal behaviors as well as differential spontaneous and vibroacoustic elicited fetal behaviors were examined in hypertensive (n = 21) compared to normotensive (n = 22) women at 33 and 36 weeks gestational age (GA). Maternal BP was negatively related to GA at birth and birth weight. On average, fetuses of hypertensive women were born 2 weeks earlier (38 weeks GA) and 340 g lighter. Maternal systolic BP was negatively related to the number of spontaneous body movements observed on ultrasound scan over 20 min and the magnitude of the fetal heart rate (FHR) acceleration elicited by a vibroacoustic stimulus. At 36 weeks GA, vibroacoustic stimulation elicited differential responding with fetuses in the hypertensive compared to the normotensive group having fewer body movements, a lower magnitude of FHR acceleration, and a lack of cardiac-body movement coupled responses. These findings suggest a relationship between maternal BP and fetal behaviors and differential functional development of sensory-motor response systems which need to be characterized in the subgroups of hypertensive disorders observed during pregnancy.     

Is there a human fetal gallbladder contractility during pregnancy?

The purpose of this study was to evaluate whether human fetal gallbladder contractility exists in the second half of pregnancy. Ultrasound examinations were performed on 54 normal pregnant women from 20 to 40 weeks of gestation. Fetal gallbladder volume was monitored every 30 min from 08:00 to 18:00 h in each patient. Maximum gallbladder volume was related linearly with gestational age between 20 and 32-35 weeks of gestation, after which a plateau was observed. Minimum gallbladder volume was unchanged throughout gestation. Functional capacity (maximum volume - minimum volume) of the fetal gallbladder increased linearly with advancing gestation until 32-35 weeks gestation, and thereafter was constant. Contractility rate [(maximum volume - minimum volume/maximum volume)x100] increased curvilinearly with advancing gestation (R(2) = 30.7%, P < 0.0001). The daily change in fetal gallbladder volume showed a typical sinusoidal pattern, and the contractility cycle of gallbladder volume was unchanged during pregnancy (3.1 +/- 0.6 h). These results suggest that there is an apparent gallbladder contractility in human fetuses in utero, and that maternal meals seem not to affect the volume of the fetal gallbladder. Further study is needed to clarify the physiological role of fetal gallbladder contractility during pregnancy.