1. Chapter 7 Fetal Growth and Development 인제대힉교 부산백병원 산부인과학 교실 R1 서 영진

2. The maternal organism responds passively to signals emanating from embronic-fetal and extraembryonic tissues The conceptus is the dynamic force in the pregnancy Essential for successful pregnancy -implantation, maternal recognition of pregnancy, immunological acceptance, endocrine function, nutrition, parturition

3. Determination of gestational age(1) Gestational age (or menstrual age) from the 1 st day of the last menstrual period : 2 weeks before ovulation & fertilization 3 weeks before implantation of the blastocyte Ovulation age :the time of ovulation Postconceptional age :the time of conception-nearly identical

4. Determination of gestational age(2) Calculate gestational age :the 1st day of the LMP~the birth of the fetus :280 days=40 weeks=9 1/3 calendar months (10 units of 28 days) A quick estimate of the EDC :LMP +7 days -3 months Trimester :3 units of 3 calendar months each

5. Morphological growth(1) Ovum, zygote, and blastocyst :during the first 2 weeks after ovulation

6. Morphological growth(2) Embryo (the 3rd weeks after fertilization) -most pregnant test: hCG (+) -embryonic disc: well defined -chorionic sac: 1 cm ·T he end of the 4 th week -embryo: 4~5 mm -chorionic sac: 2~3 cm -primitive heart (the middle oh the 4 th week) -arm & leg buds -amnion is beginning

7. Morphological growth(3) · The end of the 6 th week -embryo: 22~24mm -head > trunk -heart : completely formed -fingers & toes -the arms bend at the elbow -upper lip -external ears

8. Morphological growth(4) Fetus (occur 8 th weeks after fertilization) -the embryo-fetus: nearly 4 cm -the major portion of lung ·12 gestational weeks -uterus: palpable above the symphysis pubis -crown-rump length (CRL): 6~7 cm -center of ossification -fingers & toes: differentiated -skin & nails: developed -external genitalia: beginning -spontaneous movement

9. Morphological growth(5) ·14 gestational weeks -gender can be correctly determined ·20 gestational weeks - skin: less transparent, lanugo covers -scalp hair ·24 gestational weeks -skin: wrinkled, fat deposition -eyebrows, eyelashes -the bronchi, bronchioles, alveolar duct (the terminal sac required for gas change has not yet formed)

10. Morphological growth(6) ·28 gestational weeks -skin: red & covered with vernix caseosa -moves energetically, cries weakly -90% chance of intact survival ·36 gestational weeks -skin: rotund -excellent chance of intact suvival ·40 gestational weeks -fully developed

11. Morphological growth(7) Length of fetus -crown-rump height: the variability in the length of the legs and the difficulty of maintaining them in extension -the length is a more accurate criterion of gestational age than weight

12. Morphological growth(8) Weight of the newborn -boys > girls (100g, 3 oz) -depend on race, parental economic status, size of the parents, parity of the mother, and altitude -the second half of pregnancy ~ the 37 th week :increases in a linear manner

13. Morphological growth(9)

14. Morphological growth(10)

15. Morphological growth(11) Molding -the bones of the cranium are normally connected only by a thin layer of fibrous tissue which allows considerable shifting or sliding of each bone to accommodate the size and shape of the maternal pelvis -the location of these fontanels gives important information concerning the presentation and position of the fetus

16. Morphological growth(12) Fetal brain -myelination of the ventral roots of the cerebrospinal nerves and brain stem: begins at 6 months -the major portion of myelination: after birth

17. The fetal-maternal communication system: placental arm(1) Mother→fetus: oxygen, nutrient Fetus→mother: carbon dioxide, metabolic wastes Maternal blood: in the intervillous space Fetal blood: in the fetal capillaries in the intravillous space of chorionic villi no direct communications between the fetal blood As lung, gastrointestinal tract, kidney

18. The fetal-maternal communication system: placental arm(2) The intervillous space: maternal blood -the residual volume of the intervillous space of the term placenta: 140ml -the normal volume of the intervillous space before delivery: 280ml -uteroplacental blood flow near term: 700~900ml/min -blood pressure of intervillous spac <uterine arterial pressure >uterine venous pressure - uterine venous pressure↑: intervillous space pressure↑ (supine, standing position)

19. The fetal-maternal communication system: placental arm(3) Fetal capillaries of the intrevillous space: fetal blood - during normal labor, the rise in fetal blood pressure must be parallel to the pressure in the amnionic fluid and the intervillous space -otherwise, the capillaries in the chirionic villi would collapse

20. Placental transfer(1) Chorionic villus -the pathway from mother to fetus (1) syncytiotrophoblast (2) stroma of the intravillous space (3) fetal capillary wall -after midpregnancy (1)Langhans cell, cytotrophoblast ↓ (2)villous epithelium : syncytiotrophoblast (3)villous capillary : thinner (4)fetal vessel increase -total surface area of chorionic villi : 10 m 2 →correlation with fetal weight

21. Placental transfer(2) Regulation of placental transfer -the concentration of the substance in the maternal plasma, which it is bound to another compound, such as carrier protein -the rate of maternal blood flow through the intervillous space -the area available for exchange across the villous trophoblast epithelium -the physical properties of the tissue barrier (ex. diffusion) -the capacity of the biochemical machinery of the placenta for effecting active transfer (ex. specific receptor)

22. Placental transfer(3) -the amount of the substance metabolized by the placenta during transfer -the area for exchange across the fetal capillaries in the placenta -the concentration of the substance in the fetal blood -specific binding or carrier proteins in the fetal or maternal circulation -the rate of fetal blood flow through the villus capillaries

23. Placental transfer(4) Mechanism of transfer -molecular weight is clearly important in determining the rate of transfer by diffusion -the smaller, the more rapid -simple difussion: oxygen, carbon dioxide, water, and most(but not all) electrolyte -slow rate: insulin, steroid, thyroid hormone -high molecular weight, but transverse: Ig G (specific receptor)

24. Placental transfer(5) Transfer of oxygen & carbon dioxide - the placeta served as the lung -carbon dioxide: diffusion limited oxygen: blood-flow limited -8mL O 2 /min/ kg of fetal weight but, store for only 1 to 2 min so, this supply must be continuous

25. Placental transfer(6) -oxygen saturation of intervillous space: 65 ~75% partial pressure: 30 ~35 mmHg -the fetus normally does not suffer from lack of O 2 cardiac output: greater oxygen-carrying capacity of fetal Hb: high Hb concenturation; high -carbon dioxide: more rapidly by diffusion fetal blood has less affinity

26. Placental transfer(7) Selective transfer and facilitated diffusion -ascorbic acid : simple diffusion -iron : unidirectional treasfer -infection: viruses, bacteria, and protozoa (rubella, varicella, CMV, HIV, treponeme tuberculosis) -rarely, malignant cell

27. Nutrition of the fetus(1) -because of the small amount of york, development is dependent on nutrients obtained from the mother -so, indigested foodstuff is translated into storage forms: liver, muscle, adipose tissue -glucose→glycogen in liver & muscle amino acis: protein storage of the excess as fat: peaks in 2 nd trimester -during fasting: glycogen, adipose tissue(fatty acid) (by glucagon, norepinephrine, hPL, glucocorticosteroid, thyroxine)

28. Nutrition of the fetus(2) glucose and fetal growth -gucose is a major nutrient for fetal growth & energy -hPL: promote the mobilization and use of fatty acid blocks the peripheral uptakes and use of glucose glucose transport -by a carrier mediated, stereoapecific, nonconcen- trating process of facilitated diffusion

29. Nutrition of the fetus(3) glucose transport protein -six separate glucose transport protein (GLUT) have been discovered -GLUT-1 & GLUT-3 in plasma membrane(microvilli) of syncytiotrophoblsst glucose, insulin, and fetal macrosomia -hyperinsulinemia, IGF-1, IGFBP-3, FGF-2, increased GLUT protein expression: macrosomia

30. Nutrition of the fetus(4) free fatty acids and triglycerides -triacylglycerols does not cross the placenta but, grycerol does -most fatty acids cross the placenta by simple diffusion -the apoprotein and cholesterol ester of LDLare hydrolyzed by lysosomal enzyme in the syncytium to give:cholesterol for progesterone stnthesis free amino acid-including essential amino acids essential fatty acids, primarily linoleic acid

31. Nutrition of the fetus(5) Amino acids -in addition to the hydrolysis of LDL, the placenta is known to concentrate a large number of amino acids intracellularly Proteins -Ig G: Fc receptor on trophoblast, cross the placenta same concentration in cord & maternal area -Ig M: increase-fetal infection (immune system)

32. Nutrition of the fetus(6) Ions and trace metals -iodide transport across the placenta carrier mediated, energy-requiring avtive process -zinc : fetus > mother -copper : fetus < mother

33. Nutrition of the fetus(7) Placental sequestration of heavy metals -metallothionein-1: heavy metal binding protein (zinc, copper, lead, cadmium) -smoker: cadmium ↑- metallothionein↑ - copper binding – pseudo copper deficiency →collagen ↓ :rupture of membrane

34. Nutrition of the fetus(8) Calcium and phosphorus -actively transported from mother to fetus -PTH-rP:fetal parathyroid, placenta, tissue, decidua, myometrium adenyl cyclase activation calcium movement

35. Nutrition of the fetus(9) Vitamins -Vit. A (retinol): fetus > mother bound retinol-binding protein across the syncytium -Vit. C(ascorbic acid): energy dependent carrier mediated -Vit. D(cholecalciferol) : fetus < mother