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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 2/2019

01-02-2019 | Original Research Article

Fetal Physiologically Based Pharmacokinetic Models: Systems Information on the Growth and Composition of Fetal Organs

Authors: Khaled Abduljalil, Masoud Jamei, Trevor N. Johnson

Published in: Clinical Pharmacokinetics | Issue 2/2019

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Abstract

Background

The growth of fetal organs is a dynamic process involving considerable changes in the anatomical and physiological parameters that can alter fetal exposure to xenobiotics in utero. Physiologically based pharmacokinetic models can be used to predict the fetal exposure as time-varying parameters can easily be incorporated.

Objective

The objective of this study was to collate, analyse and integrate the available time-varying parameters needed for the physiologically based pharmacokinetic modelling of xenobiotic kinetics in a fetal population.

Methods

We performed a comprehensive literature search on the physiological development of fetal organs. Data were carefully assessed, integrated and a meta-analysis was performed to establish growth trends with fetal age and weight. Algorithms and models were generated to describe the growth of these parameter values as functions of age and/or weight.

Results

Fetal physiologically based pharmacokinetic parameters, including the size of the heart, liver, brain, kidneys, lungs, spleen, muscles, pancreas, skin, bones, adrenal and thyroid glands, thymus, gut and gonads were quantified as a function of fetal age and weight. Variability around the means of these parameters at different fetal ages was also reported. The growth of the investigated parameters was not consistent (with respect to direction and monotonicity).

Conclusion

Despite the limitations identified in the availability of some values, the data presented in this article provide a unique resource for age-dependent organ size and composition parameters needed for fetal physiologically based pharmacokinetic modelling. This will facilitate the application of physiologically based pharmacokinetic models during drug development and in the risk assessment of environmental chemicals and following maternally administered drugs or unintended exposure to environmental toxicants in this population.
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Literature
1.
Zhang Z, Unadkat JD. Development of a novel maternal-fetal physiologically based pharmacokinetic model II: verification of the model for passive placental permeability drugs. Drug Metab Dispos. 2017;45:939–46.CrossRefPubMedPubMedCentral
2.
Zhang Z, Imperial MZ, Patilea-Vrana GI, Wedagedera J, Gaohua L, Unadkat JD. Development of a novel maternal-fetal physiologically based pharmacokinetic model I: insights into factors that determine fetal drug exposure through simulations and sensitivity analyses. Drug Metab Dispos. 2017;45:920–38.CrossRefPubMedPubMedCentral
3.
O’Rahilly R, Muller F. Developmental stages in human embryos: revised and new measurements. Cells Tissues Organs. 2010;192:73–84.CrossRefPubMed
4.
Moore KL, Persaud TVN, Torchia MG. The developing human: clinically oriented embryology. 9th ed. Philadelphia (PA): Saunders, Elsevier; 2013.
5.
6.
Colbers A, Greupink R, Burger D. Pharmacological considerations on the use of antiretrovirals in pregnancy. Curr Opin Infect Dis. 2013;26:575–88.CrossRefPubMed
7.
Cox PB, Marcus MA, Bos H. Pharmacological considerations during pregnancy. Curr Opin Anaesthesiol. 2001;14:311–6.CrossRefPubMed
8.
Herbst AL, Ulfelder H, Poskanzer DC. Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med. 1971;284:878–81.CrossRefPubMed
9.
Edelman DA. Diethylstilbestrol exposure and the risk of clear cell cervical and vaginal adenocarcinoma. Int J Fertil. 1989;34:251–5.PubMed
10.
Drukker A, Guignard JP. Renal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr. 2002;14:175–82.CrossRefPubMed
11.
Brenner BM, Chertow GM. Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis. 1994;23:171–5.CrossRefPubMed
12.
Poggi SH, Ghidini A. Importance of timing of gestational exposure to methotrexate for its teratogenic effects when used in setting of misdiagnosis of ectopic pregnancy. Fertil Steril. 2011;96:669–71.CrossRefPubMed
13.
Sulik KK, Cook CS, Webster WS. Teratogens and craniofacial malformations: relationships to cell death. Development. 1988;103 Suppl.:213–31.
14.
Martin-Suarez A, Sanchez-Hernandez JG, Medina-Barajas F, Perez-Blanco JS, Lanao JM, Garcia-Cuenllas Alvarez L, et al. Pharmacokinetics and dosing requirements of digoxin in pregnant women treated for fetal supraventricular tachycardia. Expert Rev Clin Pharmacol. 2017;10:911–7.CrossRefPubMed
15.
Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2017;3:CD004454.
16.
Miyata I, Abe-Gotyo N, Tajima A, Yoshikawa H, Teramoto S, Seo M, et al. Successful intrauterine therapy for fetal goitrous hypothyroidism during late gestation. Endocr J. 2007;54:813–7.CrossRefPubMed
17.
Archie JG, Collins JS, Lebel RR. Quantitative standards for fetal and neonatal autopsy. Am J Clin Pathol. 2006;126:256–65.CrossRefPubMed
18.
Shepard TH, Shi M, Fellingham GW, Fujinaga M, FitzSimmons JM, Fantel AG, et al. Organ weight standards for human fetuses. Pediatr Pathol. 1988;8:513–24.CrossRefPubMed
19.
Jackson CM. On the prenatal growth of the human body and the relative growth of the various organs and parts. Am J Anat. 1909;9:119–65.CrossRef
20.
Luecke RH, Wosilait WD, Young JF. Mathematical representation of organ growth in the human embryo/fetus. Int J Biomed Comput. 1995;39:337–47.CrossRefPubMed
21.
Potter EL, Craig JM. Potter’s pathology of the fetus and infant. St. Louis (MO): Mosby; 1997.
22.
Valentin J. Basic anatomical and physiological data for use in radiological protection: reference values: a report of age- and gender-related differences in the anatomical and physiological characteristics of reference individuals. ICRP Publication 89. Ann ICRP. 2002;32:5–265.CrossRef
23.
Abduljalil K, Furness P, Johnson TN, Rostami-Hodjegan A, Soltani H. Anatomical, physiological and metabolic changes with gestational age during normal pregnancy: a database for parameters required in physiologically based pharmacokinetic modelling. Clin Pharmacokinet. 2012;51:365–96.CrossRefPubMed
24.
Abduljalil K, Johnson NT, Rostami-Hodjegan A. Fetal physiologically-based pharmacokinetic models: systems information on fetal biometry and gross composition. Clin Pharmacokinet (accepted).
25.
Silverwood RJ, Cole TJ. Statistical methods for constructing gestational age-related reference intervals and centile charts for fetal size. Ultrasound Obstet Gynecol. 2007;29:6–13.CrossRefPubMed
26.
Tanimura T, Nelson T, Hollingsworth RR, Shepard TH. Weight standards for organs from early human fetuses. Anat Rec. 1971;171:227–36.CrossRefPubMed
27.
Marecki B. Sexual dimorphism of the weight of internal organs in fetal ontogenesis. Anthropol Anz. 1989;47:175–84.PubMed
28.
Fujikura T, Froehlich LA. Organ-weight-brain-weight ratios as a parameter of prenatal growth: a balanced growth theory of visceras. Am J Obstet Gynecol. 1972;112:896–902.CrossRefPubMed
29.
Burdi AR, Barr M, Babler WJ. Organ weight patterns in human fetal development. Hum Biol. 1981;53:355–66.PubMed
30.
31.
Brans YW, Shannon DL. Chemical changes in human skeletal muscle during fetal development. Biol Neonate. 1981;40:21–8.CrossRefPubMed
32.
33.
34.
35.
Fee BA, Weil WB Jr. Body composition of infants of diabetic mothers by direct analysis. Ann N Y Acad Sci. 1963;110:869–97.CrossRefPubMed
36.
Fomon SJ, Haschke F, Ziegler EE, Nelson SE. Body composition of reference children from birth to age 10 years. Am J Clin Nutr. 1982;35:1169–75.CrossRefPubMed
37.
ICRP. Report of the Task Group on Reference Man. ICRP Publication 23, International Commission on Radiological Protection. Oxford: Pergamon Press; 1975.
38.
Iob V, Swanson WW. The extracellular and intracellular water in bone and cartlage. J Biol Chem. 1938;122:485–90.
39.
40.
Shah RS, Rajalakshmi R. Studies on human fetal tissues: II. Lipid composition of human fetal tissues in relation to gestational age, fetal size and maternal nutritional status. Indian J Pediatr. 1988;55:272–82.CrossRefPubMed
41.
Swanson WW. IOB V. Growth and chemical composition of the human skeleton. Am J Dis Child. 1940;59:107–11.
42.
White DR, Widdowson EM, Woodard HQ, Dickerson JW. The composition of body tissues (II): fetus to young adult. Br J Radiol. 1991;64:149–59.CrossRefPubMed
43.
Widdowson EM. Growth and composition of the fetus and newborn. In: Assali NS, editor. Biology of gestation. Vol 2. The fetus and neonate. New York (NY): Academic Press; 1968. p. 1–49.
44.
45.
Winick M. Changes in nucleic acid and protein content of the human brain during growth. Pediatr Res. 1968;2:352–5.CrossRefPubMed
46.
Valenti O, Di Prima FA, Renda E, Faraci M, Hyseni E, De Domenico R, et al. Fetal cardiac function during the first trimester of pregnancy. J Prenat Med. 2011;5:59–62.PubMedPubMedCentral
47.
Thayyil S, Schievano S, Robertson NJ, Jones R, Chitty LS, Sebire NJ, et al. A semi-automated method for non-invasive internal organ weight estimation by post-mortem magnetic resonance imaging in fetuses, newborns and children. Eur J Radiol. 2009;72:321–6.CrossRefPubMed
48.
Blackburn ST. Maternal, fetal and neonatal physiology: a clinical perspective. 3rd ed. Philadelphia: Saunders Elsevier; 2007.
49.
Khwaja OS, Pomeroy SL, Ullrich NJ. Development of the nervous system. In: Polin RA, Fox WW, Abman SH, editors. Fetal and neonatal physiology. 4th ed. Philadelphia (PA): Elsevier; 2011. p. 1745–62.CrossRef
50.
Samuelsen GB, Larsen KB, Bogdanovic N, Laursen H, Graem N, Larsen JF, et al. The changing number of cells in the human fetal forebrain and its subdivisions: a stereological analysis. Cereb Cortex. 2003;13:115–22.CrossRefPubMed
51.
Breeze AC, Gallagher FA, Lomas DJ, Smith GC, Lees CC. Postmortem fetal organ volumetry using magnetic resonance imaging and comparison to organ weights at conventional autopsy. Ultrasound Obstet Gynecol. 2008;31:187–93.CrossRefPubMed
52.
Duck FA. Physical properties of tissue. London: Academic; 1990.
53.
54.
Fanni D, Fanos V, Ambu R, Lai F, Gerosa C, Pampaloni P, et al. Overlapping between CYP3A4 and CYP3A7 expression in the fetal human liver during development. J Matern Fetal Neonatal Med. 2014:1–5.
55.
Hakkola J, Raunio H, Purkunen R, Saarikoski S, Vahakangas K, Pelkonen O, et al. Cytochrome P450 3A expression in the human fetal liver: evidence that CYP3A5 is expressed in only a limited number of fetal livers. Biol Neonate. 2001;80:193–201.CrossRefPubMed
56.
Hakkola J, Pasanen M, Purkunen R, Saarikoski S, Pelkonen O, Maenpaa J, et al. Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver. Biochem Pharmacol. 1994;48:59–64.CrossRefPubMed
57.
Hines RN. The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacol Ther. 2008;118:250–67.CrossRefPubMed
58.
Gasser B, Mauss Y, Ghnassia JP, Favre R, Kohler M, Yu O, et al. A quantitative study of normal nephrogenesis in the human fetus: its implication in the natural history of kidney changes due to low obstructive uropathies. Fetal Diagn Ther. 1993;8:371–84.CrossRefPubMed
59.
Rosati P, Guariglia L. Transvaginal sonographic assessment of the fetal urinary tract in early pregnancy. Ultrasound Obstet Gynecol. 1996;7:95–100.CrossRefPubMed
60.
Vlajkoviç S, Dakoviç-Bjelakoviç M, Čukuranoviç R, Krivokuça D. The average volume of fetal kidney during different periods of gestation. Acta Medica Medianae. 2005;44:47–50.
61.
Geelhoed JJ, Taal HR, Steegers EA, Arends LR, Lequin M, Moll HA, et al. Kidney growth curves in healthy children from the third trimester of pregnancy until the age of two years: the Generation R Study. Pediatr Nephrol. 2010;25:289–98.CrossRefPubMedPubMedCentral
62.
Jovevska S, Tofoski G. Comparison between ultrasound (US) and macrodisection measurements of human foetal kidney. Prilozi. 2008;29:337–44.PubMed
63.
Vlajkovic S, Vasovic L, Dakovic-Bjelakovic M, Cukuranovic R. Age-related changes of the human fetal kidney size. Cells Tissues Organs. 2006;182:193–200.CrossRefPubMed
64.
Vlajkovic S, Dakovic-Bjelakovic M, Cukuranovic R, Popovic J. Evaluation of absolute volume of human fetal kidney’s cortex and medulla during gestation. Vojnosanit Pregl. 2005;62:107–11.CrossRefPubMed
65.
Hinchliffe SA, Sargent PH, Howard CV, Chan YF, van Velzen D. Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. Lab Invest. 1991;64:777–84.PubMed
66.
Haycock GB. Development of glomerular filtration and tubular sodium reabsorption in the human fetus and newborn. Br J Urol. 1998;81(Suppl. 2):33–8.CrossRefPubMed
67.
Seikaly MG, Arant BS Jr. Development of renal hemodynamics: glomerular filtration and renal blood flow. Clin Perinatol. 1992;19:1–13.CrossRefPubMed
68.
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;161:1264–6.CrossRefPubMed
69.
Manalich R, Reyes L, Herrera M, Melendi C, Fundora I. Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int. 2000;58:770–3
70.
Trnka P, Hiatt MJ, Tarantal AF, Matsell DG. Congenital urinary tract obstruction: defining markers of developmental kidney injury. Pediatr Res. 2012;72:446–54.CrossRefPubMed
71.
Sulak O, Cankara N, Malas MA, Koyuncu E, Desdicioglu K. Anatomical development of urinary bladder during the fetal period. Clin Anat. 2008;21:683–90.CrossRefPubMed
72.
Hedriana HL, Moore TR. Ultrasonographic evaluation of human fetal urinary flow rate: accuracy limits of bladder volume estimations. Am J Obstet Gynecol. 1994;170:1250–4.CrossRefPubMed
73.
Woolf AS. Perspectives on human perinatal renal tract disease. Semin Fetal Neonatal Med. 2008;13:196–201.CrossRefPubMed
74.
Lee SM, Park SK, Shim SS, Jun JK, Park JS, Syn HC. Measurement of fetal urine production by three-dimensional ultrasonography in normal pregnancy. Ultrasound Obstet Gynecol. 2007;30:281–6.CrossRefPubMed
75.
Maged AM, Abdelmoneim A, Said W, Mostafa WA. Measuring the rate of fetal urine production using three-dimensional ultrasound during normal pregnancy and pregnancy-associated diabetes. J Matern Fetal Neonatal Med. 2014;27(17):1790–4.CrossRefPubMed
76.
Touboul C, Boulvain M, Picone O, Levaillant JM, Frydman R, Senat MV. Normal fetal urine production rate estimated with 3-dimensional ultrasonography using the rotational technique (virtual organ computer-aided analysis). Am J Obstet Gynecol. 2008;199(1):57.e1–5.
77.
Bouwens L, Lu WG, De Krijger R. Proliferation and differentiation in the human fetal endocrine pancreas. Diabetologia. 1997;40:398–404.CrossRefPubMed
78.
Robb P. The development of the islets of Langerhans in the human foetus. Q J Exp Physiol Cogn Med Sci. 1961;46:335–43.PubMed
79.
Desdicioglu K, Malas MA, Evcil EH. Foetal development of the pancreas. Folia Morphol (Warsz). 2010;69:216–24.PubMed
80.
Krakowiak-Sarnowska E, Flisinski P, Szpinda M, Sarnowski J, Lisewski P, Flisinski M. Morphometry of the pancreas in human foetuses. Folia Morphol (Warsz). 2005;64:29–32.PubMed
81.
Langston C, Kida K, Reed M, Thurlbeck WM. Human lung growth in late gestation and in the neonate. Am Rev Respir Dis. 1984;129:607–13.PubMed
82.
Votino C, Verhoye M, Segers V, Cannie M, Bessieres B, Cos T, et al. Fetal organ weight estimation by postmortem high-field magnetic resonance imaging before 20 weeks’ gestation. Ultrasound Obstet Gynecol. 2012;39:673–8.CrossRefPubMed
83.
Ishak N, Sozo F, Harding R, De Matteo R. Does lung development differ in male and female fetuses? Exp Lung Res. 2014;40:30–9.CrossRefPubMed
84.
Blackfan KD. Growth and development of the child. Part II: anatomy and physiology. Report of the Committee on Growth and Development. New York (NY): The Century Company; 1933.
85.
Modi N, Hutton JL. Urinary creatinine excretion and estimation of muscle mass in infants of 25–34 weeks gestation. Acta Paediatr Scand. 1990;79:1156–62.CrossRefPubMed
86.
Malina RM. Growth of muscle tissue and muscle mass. In: Falkner F, Tanner JM, editors. Human growth: a comprehensive treatise. 2nd ed. New York (NY): Plenum Press; 1986. p. 77–99.
87.
Bruce A. Skeletal muscle lipids. II. Changes in phospholipid composition in man from fetal to middle age. J Lipid Res. 1974;15:103–8.PubMed
88.
Dale BA, Holbrook KA, Kimball JR, Hoff M, Sun TT. Expression of epidermal keratins and filaggrin during human fetal skin development. J Cell Biol. 1985;101:1257–69.CrossRefPubMed
89.
Li J, Fu X, Sun X, Sun T, Sheng Z. The interaction between epidermal growth factor and matrix metalloproteinases induces the development of sweat glands in human fetal skin. J Surg Res. 2002;106:258–63.CrossRefPubMed
90.
Roe HE. The weight of the skin and tela subcutanea of the human fetus. Anat Rec. 1933;55:127–37.CrossRef
91.
Usher R, McLean F. Intrauterine growth of live-born Caucasian infants at sea level: standards obtained from measurements in 7 dimensions of infants born between 25 and 44 weeks of gestation. J Pediatr. 1969;74:901–10.CrossRefPubMed
92.
Wilmer HA. Quantitative growth of skin and subcutaneous tissue in relation to human surface area. Proc Soc Exp Biol Med. 1940;43:386–8.CrossRef
93.
Baker PN, Johnson IR, Gowland PA, Hykin J, Harvey PR, Freeman A, et al. Fetal weight estimation by echo-planar magnetic resonance imaging. Lancet. 1994;343:644–5.CrossRefPubMed
94.
Friis-Hansen B. Body composition during growth: in vivo measurements and biochemical data correlated to differential anatomical growth. Pediatrics. 1971;47:Suppl. 2:264.
95.
Lapillonne AA, Glorieux FH, Salle BL, Braillon PM, Chambon M, Rigo J, et al. Mineral balance and whole body bone mineral content in very low-birth-weight infants. Acta Paediatr. 1994;405:117–22.CrossRef
96.
Demarini S, Koo WW, Hockman EM. Bone, lean and fat mass of newborn twins versus singletons. Acta Paediatr. 2006;95:594–9.CrossRefPubMed
97.
Lapillonne A, Braillon P, Claris O, Chatelain PG, Delmas PD, Salle BL. Body composition in appropriate and in small for gestational age infants. Acta Paediatr. 1997;86:196–200.CrossRefPubMed
98.
Salle BL, Rauch F, Travers R, Bouvier R, Glorieux FH. Human fetal bone development: histomorphometric evaluation of the proximal femoral metaphysis. Bone. 2002;30:823–8.CrossRefPubMed
99.
Harvey NC, Mahon PA, Robinson SM, Nisbet CE, Javaid MK, Crozier SR, et al. Different indices of fetal growth predict bone size and volumetric density at 4 years of age. J Bone Miner Res. 2010;25:920–7.PubMed
100.
Walsh JM, Kilbane M, McGowan CA, McKenna MJ, McAuliffe FM. Pregnancy in dark winters: implications for fetal bone growth? Fertil Steril. 2013;99:206–11.CrossRefPubMed
101.
Kara SA, Toppare MF. Ultrasonographic dimensions of the vertical span of the fetal iliac bone and relationship with some fetal parameters. Prenatal Diagn. 1998;18:127–32.CrossRef
102.
Scheuer JL, Musgrave JH, Evans SP. The estimation of late fetal and perinatal age from limb bone length by linear and logarithmic regression. Ann Hum Biol. 1980;7:257–65.CrossRefPubMed
103.
Trotter M, Peterson RR. Weight of bone in the fetus during the last half of pregnancy. Clin Orthop Relat Res. 1969;65:46–50.CrossRefPubMed
104.
105.
Braillon PM, Buenerd A, Lapillonne A, Bouvier R. Skeletal and total body volumes of human fetuses: assessment of reference data by spiral CT. Pediatr Radiol. 2002;32:354–9.CrossRefPubMed
106.
107.
Wilpshaar J, Joekes EC, Lim FT, Van Leeuwen GA, Van den Boogaard PJ, Kanhai HH, et al. Magnetic resonance imaging of fetal bone marrow for quantitative definition of the human fetal stem cell compartment. Blood. 2002;100:451–7.CrossRefPubMed
108.
Bronshtein M, Tzidony D, Dimant M, Hajos J, Jaeger M, Blumenfeld Z. Transvaginal ultrasonographic measurements of the fetal adrenal glands at 12 to 17 weeks of gestation. Am J Obstet Gynecoly. 1993;169:1205–10.CrossRef
109.
110.
De Leon-Luis J, Gamez F, Pintado P, Antolin E, Perez R, Ortiz-Quintana L, et al. Sonographic measurements of the thymus in male and female fetuses. J Ultrasound Med. 2009;28:43–8.CrossRefPubMed
111.
Zalel Y, Gamzu R, Mashiach S, Achiron R. The development of the fetal thymus: an in utero sonographic evaluation. Prenat Diagn. 2002;22:114–7.CrossRefPubMed
112.
Liberti EA, Villa N, Melhem SA, Matson E, Konig B Jr, Adamo J. A morphometrical study of human fetal thymus. Z Mikrosk Anat Forsch. 1989;103:309–15.PubMed
113.
Patel J, Landers K, Li H, Mortimer RH, Richard K. Thyroid hormones and fetal neurological development. J Endocrinol. 2011;209:1–8.CrossRefPubMed
114.
115.
Cohen O, Pinhas-Hamiel O, Sivan E, Dolitski M, Lipitz S, Achiron R. Serial in utero ultrasonographic measurements of the fetal thyroid: a new complementary tool in the management of maternal hyperthyroidism in pregnancy. Prenat Diagn. 2003;23:740–2.CrossRefPubMed
116.
Ares S, Pastor I, Quero J, Morreale de Escobar G. Thyroid gland volume as measured by ultrasonography in preterm infants. Acta Paediatr. 1995;84:58–62.CrossRefPubMed
117.
Bocian-Sobkowska J, Wozniak W, Malendowicz LK. Morphometric studies on the development of the human thyroid gland. II. The late fetal life. Histol Histopathol. 1997;12:79–84.PubMed
118.
Guihard-Costa AM, Menez F, Delezoide AL. Organ weights in human fetuses after formalin fixation: standards by gestational age and body weight. Pediatr Dev Pathol. 2002;5:559–78.CrossRefPubMed
119.
120.
Ozguner G, Sulak O. Size and location of thyroid gland in the fetal period. Surg Radiol Anat. 2014;36:359–67.CrossRefPubMed
121.
Savin-Žegarac S, Cvejic D, Nedić O, Radosavljević R, Ivana MP. Iodine and iodothyronine content in human neonate thyroid gland. Arch Biol Sci. 2002;54(3–4):69–74.CrossRef
122.
Shepard TH, Andersen HJ, Andersen H. The human fetal thyroid. I. Its weight in relation to body weight, crown-rump length, foot length and estimated gestation age. Anat Rec. 1964;148:123–8.CrossRefPubMed
123.
Valentin J. Basic anatomical and physiological data for use in radiological protection: reference values: ICRP Publication 89. Ann ICRP. 2002;32:1–277.CrossRef
124.
Seely BL, Burrow GN. Thyroid disease and pregnancy. In: Creasy RK, Resnik R, editors. Maternal fetal medicine: principle and practice. Philadelphia (PA): WB Saunders; 1994. p. 979–1001.
125.
Weaver LT. Anatomy and embryology. In: Walker WA, Dune PR, Hamilton RJ, editors. Pediatric gastrointestinal disease. 2nd ed. St. Louis (MO): Mosby; 1996.
126.
Pritchard JA. Fetal swallowing and amniotic fluid volume. Obstet Gynecol. 1966;28:606–10.PubMed
127.
Menard D. Functional development of the human gastrointestinal tract: hormone- and growth factor-mediated regulatory mechanisms. Can J Gastroenterol. 2004;18:39–44.CrossRefPubMed
128.
Grand RJ, Watkins JB, Torti FM. Development of the human gastrointestinal tract: a review. Gastroenterology. 1976;70:790–810.PubMedCrossRef
129.
Bates MD, Balistreri WF. The gastrointestinal tract: development of the human digestive system. In: Fanaroff AA, Martin RJ, editors. Neonatal-perinatal medicine: diseases of the fetus and infant. 7th ed. St. Louis (MO): Mosby; 2002.
130.
Malo C. Multiple pathways for amino acid transport in brush border membrane vesicles isolated from the human fetal small intestine. Gastroenterology. 1991;100:1644–52.CrossRefPubMed
131.
Lebenthal A, Lebenthal E. The ontogeny of the small intestinal epithelium. JPEN J Parenter Enteral Nutr. 1999;23(5 Suppl.):S3–6.CrossRefPubMed
132.
Goldstein I, Reece EA, Yarkoni S, Wan M, Green JL, Hobbins JC. Growth of the fetal stomach in normal pregnancies. Obstet Gynecol. 1987;70:641–4.PubMed
133.
Nagata S, Koyanagi T, Fukushima S, Akazawa K, Nakano H. Change in the three-dimensional shape of the stomach in the developing human fetus. Early Hum Dev. 1994;37:27–38.CrossRefPubMed
134.
Gworys B, Jeka S, Brukiewa R, Rymko M. Dynamics of stomach growth in the human fetal period: a post mortem study. Int J Morphol. 2012;30:461–6.CrossRef
135.
Sase M, Asada H, Okuda M, Kato H. Fetal gastric size in normal and abnormal pregnancies. Ultrasound Obstet Gynecol. 2002;19:467–70.CrossRefPubMed
136.
Hata T, Tanaka H, Noguchi J, Inubashiri E, Yanagihara T, Kondoh S. Three-dimensional sonographic volume measurement of the fetal stomach. Ultrasound Med Biol. 2010;36:1808–12.CrossRefPubMed
137.
Ben-Haroush A, Yogev Y, Peled Y, Bar J, Hod M, Pardo J. Correlation between fetal gastric size and amniotic fluid volume. J Clin Ultrasound. 2005;33:119–22.CrossRefPubMed
138.
Vierordt H. Anatomische Physiologische Und Physikalische Daten Und Tabellen Zum Gebrauche Für Mediziner. Jena: Verlag von Gustav Fischer; 1906.
139.
Touloukian RJ, Smith GJ. Normal intestinal length in preterm infants. J Pediatr Surg. 1983;18:720–3.CrossRefPubMed
140.
Struijs MC, Diamond IR, de Silva N, Wales PW. Establishing norms for intestinal length in children. J Pediatr Surg. 2009;44:933–8.CrossRefPubMed
141.
Shanklin DR, Cooke RJ. Effects of intrauterine growth on intestinal length in the human fetus. Biol Neonate. 1993;64:76–81.CrossRefPubMed
142.
Marnerides A, Ghazi S, Sundberg A, Papadogiannakis N. Development of fetal intestinal length during 2nd-trimester in normal and pathologic pregnancies. Pediatr Dev Pathol. 2012;15:24–9.CrossRefPubMed
143.
FitzSimmons J, Chinn A, Shepard TH. Normal length of the human fetal gastrointestinal tract. Pediatr Pathol. 1988;8:633–41.CrossRefPubMed
144.
Desdicioglu K, Malas MA, Evcil EH. Development of the fetal duodenum: a postmortem study. Fetal Diagn Ther. 2009;26:16–23.CrossRefPubMed
145.
Rao-Mohandas KG, Somayaji SN, Bairy KL, Nayak S, Vincent R. A study to evaluate the relationship between the age of the fetus and intestinal length. Eur J Anat. 2006;10:151–2.
146.
147.
Malas MA, Aslankoc R, Ungor B, Sulak O, Candir O. The development of jejunum and ileum during the fetal period. Early Hum Dev. 2003;74:109–24.CrossRefPubMed
148.
Herlinger H. Anatomy of the small intestine. In: Herlinger H, Maglinte D, Birnbaum BAE, editors. Clinical imaging of the small intestine. 2nd ed. New York (NY): Springer-Verlag New York, Inc.; 1999: p. 3–12.
149.
Shah RS, Rajalakshmi R. Studies on human fetal tissues: I. Fetal weight and tissue weights in relation to gestational age, fetal size and maternal nutritional status. Indian J Pediatr. 1988;55:261–71.CrossRefPubMed
150.
Zilianti M, Fernandez S. Correlation of ultrasonic images of fetal intestine with gestational age and fetal maturity. Obstet Gynecol. 1983;62:569–73.PubMed
151.
Nyberg DA, Mack LA, Patten RM, Cyr DR. Fetal bowel: normal sonographic findings. J Ultrasound Med. 1987;6:3–6.CrossRefPubMed
152.
Malas MA, Aslankoc R, Ungor B, Sulak O, Candir O. The development of large intestine during the fetal period. Early Hum Dev. 2004;78:1–13.CrossRefPubMed
153.
Aoki S, Hata T, Senoh D, KM, Hata K, Takamiya O, et al. Ultrasonographic measurement of fetal colon. Acta Neanatol Jpn. 1989;25:559–62.
154.
Goldstein I, Lockwood C, Hobbins JC. Ultrasound assessment of fetal intestinal development in the evaluation of gestational age. Obstet Gynecol. 1987;70:682–6.PubMed
155.
156.
Malas MA, Gokcimen A, Sulak O. Growing of caecum and vermiform appendix during the fetal period. Fetal Diagn Ther. 2001;16:173–7.CrossRefPubMed
157.
Zalel Y, Perlitz Y, Gamzu R, Peleg D, Ben-Ami M. In-utero development of the fetal colon and rectum: sonographic evaluation. Ultrasound Obstet Gynecol. 2003;21:161–4.CrossRefPubMed
158.
Rubesova E, Vance CJ, Ringertz HG, Barth RA. Three-dimensional MRI volumetric measurements of the normal fetal colon. AJR Am J Roentgenol. 2009;192:761–5.CrossRefPubMed
159.
Clatworthy H Jr, Anderson RG. Development and growth of the human embryo and fetus: a graphic representation of some aspects. Am J Dis Child. 1944;67(3):167–75.CrossRef
160.
161.
Scammon RE. Some graphs and tables illustrating the growth of the human stomach. Am J Dis Child. 1919;17:395–422.
162.
Hata K, Hata T, Kitao M. Ultrasonographic identification and measurement of the human fetal pancreas in utero. Int J Gynaecol Obstet. 1988;26:61–4.CrossRefPubMed
163.
Sampaio FJ. Analysis of kidney volume growth during the fetal period in humans. Urol Res. 1992;20:271–4.CrossRefPubMed
164.
Xu D, Chen M, Pan XL, Xia LP, Wang H. Dexamethasone induces fetal developmental toxicity through affecting the placental glucocorticoid barrier and depressing fetal adrenal function. Environ Toxicol Pharmacol. 2011;32:356–63.CrossRefPubMed
165.
Ping J, Wang JF, Liu L, Yan YE, Liu F, Lei YY, et al. Prenatal caffeine ingestion induces aberrant DNA methylation and histone acetylation of steroidogenic factor 1 and inhibits fetal adrenal steroidogenesis. Toxicology. 2014;321:53–61.CrossRefPubMed
166.
Sayed MM. Effect of prenatal exposure to nicotine/thiocyanate on the pituitary–adrenal axis of 1-month-old rat offspring. Egypt J Histol. 2016;39:307–16.CrossRef
167.
Viau M, Collin-Faure V, Richaud P, Ravanat JL, Candeias SM. Cadmium and T cell differentiation: limited impact in vivo but significant toxicity in fetal thymus organ culture. Toxicol Appl Pharmacol. 2007;223:257–66.CrossRefPubMed
168.
Holladay SD, Smith BJ. Fetal hematopoietic alterations after maternal exposure to benzo[a]pyrene: a cytometric evaluation. J Toxicol Environ Health. 1994;42:259–73.CrossRefPubMed
169.
Holladay SD, Luster MI. Alterations in fetal thymic and liver hematopoietic cells as indicators of exposure to developmental immunotoxicants. Environ Health Perspect. 1996;104(Suppl. 4):809–13.PubMedPubMedCentral
170.
Thayyil S, Cleary JO, Sebire NJ, Scott RJ, Chong K, Gunny R, et al. Post-mortem examination of human fetuses: a comparison of whole-body high-field MRI at 9.4 T with conventional MRI and invasive autopsy. Lancet. 2009;374:467–75.CrossRefPubMed
171.
Araujo Junior E, Nardozza LM, Rolo LC, Nowak PM, Filho JB, Moron AF. Reference range of embryo volume by 3-D sonography using the XI VOCAL method at 7 to 10 + 6 weeks of pregnancy. Am J Perinatol. 2010;27:501–5.CrossRefPubMed
172.
Kehl S, Kalk AL, Eckert S, Schaible T, Sutterlin M, Neff W, et al. Assessment of lung volume by 3-dimensional sonography and magnetic resonance imaging in fetuses with congenital diaphragmatic hernias. J Ultrasound Med. 2011;30:1539–45.CrossRefPubMed
173.
Strizek B, Cos Sanchez T, Khalife J, Jani J, Cannie M. Impact of operator experience on the variability of fetal lung volume estimation by 3D-ultrasound (VOCAL) and magnetic resonance imaging in fetuses with congenital diaphragmatic hernia. J Matern Fetal Neonatal Med. 2015;28(7):858–64.CrossRefPubMed
174.
Won HS, Lee SJ, Jun SM. Clinical application and usefulness of XI VOCAL in volume measurement [White paper]. Seoul: Medison Co, Ltd; 2006: 1–3.
175.
Barreto EQ, Milani HJ, Haratz KK, Araujo Junior E, Nardozza LM, Moron AF. Reference intervals for fetal heart volume from 3-dimensional sonography using the extended imaging virtual organ computer-aided analysis method at gestational ages of 20 to 34 weeks. J Ultrasound Med. 2012;31:673–8.CrossRefPubMed
176.
Chang FM, Hsu KF, Ko HC, Yao BL, Chang CH, Yu CH, et al. Fetal heart volume assessment by three-dimensional ultrasound. Ultrasound Obstet Gynecol. 1997;9:42–8.CrossRefPubMed
177.
Cussen L, Scurry J, Mitropoulos G, McTigue C, Gross J. Mean organ weights of an Australian population of fetuses and infants. J Paediatr Child Health. 1990;26:101–3.CrossRefPubMed
178.
Gruenwald P, Hoang Ngoc M. Evaluation of body and organ weights in perinatal pathology. I. Normal standards derived from autopsies. Am J Clin Pathol. 1960;34:247–53.CrossRefPubMed
179.
Hansen K, Sung CJ, Huang C, Pinar H, Singer DB, Oyer CE. Reference values for second trimester fetal and neonatal organ weights and measurements. Pediatr Dev Pathol. 2003;6:160–7.CrossRefPubMed
180.
Marecki B. Changes in the weight of internal organs in the fetal ontogenesis. Z Morphol Anthropol. 1989;77:235–45.PubMed
181.
Maroun LL, Graem N. Autopsy standards of body parameters and fresh organ weights in nonmacerated and macerated human fetuses. Pediatr Dev Pathol. 2005;8:204–17.CrossRefPubMed
182.
Mitropoulos G, Scurry J, Cussen L. Organ weight/bodyweight ratios: growth rates of fetal organs in the latter half of pregnancy with a simple method for calculating mean organ weights. J Paediatr Child Health. 1992;28:236–9.CrossRefPubMed
183.
Peralta CF, Cavoretto P, Csapo B, Falcon O, Nicolaides KH. Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12–32 weeks’ gestation. Ultrasound Obstet Gynecol. 2006;27:128–33.CrossRefPubMed
184.
Phillips JB, Billson VR, Forbes AB. Autopsy standards for fetal lengths and organ weights of an Australian perinatal population. Pathology. 2009;41:515–26.CrossRefPubMed
185.
Schulz DM, Giordano DA, Schulz DH. Weights of organs of fetuses and infants. Arch Pathol. 1962;74:244–50.PubMed
186.
Ozguner G, Sulak O, Koyuncu E. A morphometric study of suprarenal gland development in the fetal period. Surg Radiol Anat. 2012;34:581–7.CrossRefPubMed
187.
Singer DB, Sung CJ, Wigglesworth JS. Fetal growth and maturation: with standards for body and organ development. In: Wigglesworth JS, Singer DB, editors. Textbook of fetal and perinatal pathology. London: Blackwell Scientific Publications; 1991. p. 11–47.
188.
Duncan KR, Issa B, Moore R, Baker PN, Johnson IR, Gowland PA. A comparison of fetal organ measurements by echo-planar magnetic resonance imaging and ultrasound. BJOG. 2005;112:43–9.CrossRefPubMed
189.
Gielecki J, Zurada A, Kozlowska H, Nowak D, Loukas M. Morphometric and volumetric analysis of the middle cerebral artery in human fetuses. Acta Neurobiol Exp (Wars). 2009;69:129–37.PubMed
190.
Boito SM, Laudy JA, Struijk PC, Stijnen T, Wladimiroff JW. Three-dimensional US assessment of hepatic volume, head circumference, and abdominal circumference in healthy and growth-restricted fetuses. Radiology. 2002;223:661–5.CrossRefPubMed
191.
Casey ML, Carr BR. Growth of the kidney in the normal human fetus during early gestation. Early Hum Dev. 1982;6:11–4.CrossRefPubMed
192.
Jeanty P, Dramaix-Wilmet M, Elkhazen N, Hubinont C, van Regemorter N. Measurements of fetal kidney growth on ultrasound. Radiology. 1982;144:159–62.CrossRefPubMed
193.
Michielsen K, Meersschaert J, De Keyzer F, Cannie M, Deprest J, Claus F. MR volumetry of the normal fetal kidney: reference values. Prenatal Diagn. 2010;30:1044–8.CrossRef
194.
Tedesco GD, Bussamra LC, Araujo Junior E, Britto IS, Nardozza LM, Moron AF, et al. Reference range of fetal renal volume by three-dimensional ultrasonography using the VOCAL method. Fetal Diagn Ther. 2009;25:385–91.CrossRefPubMed
195.
van Vuuren SH, Damen-Elias HA, Stigter RH, van der Doef R, Goldschmeding R, de Jong TP, et al. Size and volume charts of fetal kidney, renal pelvis and adrenal gland. Ultrasound Obstet Gynecol. 2012;40:659–64.CrossRefPubMed
196.
Bahmaie A, Hughes SW, Clark T, Milner A, Saunders J, Tilling K, et al. Serial fetal lung volume measurement using three-dimensional ultrasound. Ultrasound Obstet Gynecol. 2000;16:154–8.CrossRefPubMed
197.
Gerards FA, Engels MA, Twisk JW, van Vugt JM. Normal fetal lung volume measured with three-dimensional ultrasound. Ultrasound Obstet Gynecol. 2006;27:134–44.CrossRefPubMed
198.
Moeglin D, Talmant C, Duyme M, Lopez AC. Fetal lung volumetry using two- and three-dimensional ultrasound. Ultrasound Obstet Gynecol. 2005;25:119–27.CrossRefPubMed
199.
Pohls UG, Rempen A. Fetal lung volumetry by three-dimensional ultrasound. Ultrasound Obstet Gynecol. 1998;11:6–12.CrossRefPubMed
200.
Ruano R, Joubin L, Aubry MC, Thalabard JC, Dommergues M, Dumez Y, et al. A nomogram of fetal lung volumes estimated by 3-dimensional ultrasonography using the rotational technique (virtual organ computer-aided analysis). J Ultrasound Med. 2006;25:701–9.CrossRefPubMed
201.
Hata T, Kuno A, Dai SY, Inubashiri E, Hanaoka U, Kanenishi K, et al. Three-dimensional sonographic volume measurement of the fetal spleen. J Obstet Gynaecol Res. 2007;33:600–5.CrossRefPubMed
202.
Welcker H, Brandt A. Gewichtswerthe der Körper-organe bei dem Menschen und den Thieren: ein Beitrag zur vergleichenden Anatomie und Entwickelungsgeschichte. Arch f Anthrop. 1902;28:1–89.
203.
Trotter M, Peterson RR. Weight of bone in the fetus: a preliminary report. Growth. 1968;32:83–90.PubMed
204.
Ozguner G, Sulak O. Size and location of thyroid gland in the fetal period. Surg Radiol Anat. 2014;36(4):359–67.CrossRefPubMed
Metadata
Title
Fetal Physiologically Based Pharmacokinetic Models: Systems Information on the Growth and Composition of Fetal Organs
Authors
Khaled Abduljalil
Masoud Jamei
Trevor N. Johnson
Publication date
01-02-2019
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 2/2019
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-018-0685-y

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