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Fetal development Morphological/ physiological/ biochemical aspect and clinical correlation รองศาสตราจารย์ นายแพทย์ อติวทุ ธ กมุทมาศ Morphological aspect and clinical correlation Dating of pregnancy Obstetricians : Menstrual age/ gestational age : LMP (first day) = 2 wk before ovulation/ fertilization , 3 wk before implantation of blastocyst Embryologists : ovulation age/ postconception age Clinical correlation EDC = LMP + 7 days – 3 months Pregnant duration = 40 wk/ 280 d/ 9 1/3 mo 3 trimesters : 1 / 2 / 3 Before 28 wk = abortion (USA < 20 wk) 28 – 36 wk = preterm 37 – 42 wk = term > 42 wk = postterm The ovum, zygote, blastocyst Ovulation Fertilization of the ovum Formation of free blastocyst Implantation of the blastocyst Clinical correlation Time to test for pregnancy : serum hCG = 3 wk (gestational age) (not for UPT) Implantation bleeding (Hartman’s sign) : 3 wk GA Wrong date by implantation bleeding Not include in threatened abortion The embryo At the beginning of the 3rd wk after ovulation (3 wk OA/ 5 wk GA) Embryonic disc is well defined Body stalk is differentiated The chorionic sac = 1 cm Clinical correlation Time for UPT positive Begin to detect by ultrasound : vaginal probe/ abdominal probe GA calculated by mean sac diameter Sac 1 cm = 5 wk GA Sac 2 cm = 6 wk GA Sac 3 cm = 7 wk GA The embryo (cont) 4th wk Ovulation age (6 wk GA) chorionic sac = 2-3 cm in diameter embryo = 4-5 mm in length fetal heart beat = movement 8 wk GA Embryo = 22-24 mm in length Head found and quite large Clinical correlation GA calculated by CRL (crown rump length) CRL (cm) + 6.5 = GA (wk) If bleeding = threatened abortion/ blighted ovum/ dead embryo can be diagnosed by ultrasound at this time (after 6 wk GA) GA by CRL is accurate as ± 4.7 days The fetus 8 wk after ovulation (GA 10 wk) 4 cm long Major structures are formed 12 weeks fetus CRL = 6-7 cm Centers of ossification appear Fingers and toes are differentiated Nails present Rudiments of hair appear External genitalia begins to show Clinical correlation Uterus begins to be palpable (as 1/3 above pubic symphysis) Morning sickness is improved 16 weeks fetus CRL = 12 cm Wt = 110 gm Clinical correlation Uterus 2/3 above pubic symphysis Doing well Quickening Primigravida = 18-20 wk Multiparity = 16-18 wk Fetal heart beat detected by stethoscope Fetal gender detected by ultrasound 20 weeks fetus Mid point of pregnancy Wt = 300 gm Fetal skin has become less transparent Lanugo hairs cover entire body Scalp hair visible Clinical correlation Uterus at umbilicus Midpoint of pregnancy : size of uterus is mostly reliable regardless of factors such as thickness of abdominal wall, experience of the examiners 24 weeks fetus Wt = 630 gm Skin : wrinkled Fat : deposit Eyebrows / eyelashes recognizable Clinical correlation Uterus size = 1/4 above umbilicus (24 cm by Jeminez) If delivered = baby (newborn/ infant) attempt to breathe , but almost always dies shortly after birth 28 weeks fetus CRL = 25 cm Wt = 1100 gm Skin : red, covered with vernix caseosa Pupillary membrane has just disappeared from the eyes Clinical correlation Uterus size = 2/4 above umbilicus, 28 cm Viable period Infant born : limbs quite energetic, cries weakly, survive with expert care (NICU) 32 weeks fetus 28 cm long 1800 gm Skin still red and wrinkle 36 weeks fetus 32 cm 2500 gm More deposition of subcutaneous fat : wrinkle is lost 40 weeks fetus 36 cm 3400 gm (average) Full term (37 - 42 weeks GA) After 42 weeks Postterm Skin become wrinkle again Amniotic fluid decreased Placental dysfunction Fetal compromised Fetal death in utero/ still birth Fertilization Fertilized ovum Blastocyst formation Embryo development Biochemical aspect and clinical correlation Nutrition of the fetus First 2 months : embryo consists almost entirely of water In later months : relatively more solids are added Because small amount of yolk : most nutrients early obtained from mother During the first few days after implantation : the nutrition of the blastocyst arises directly from the interstitial fluid of the endometrium and from the surrounding maternal tissue Within the next week : intervillous spaces are formed, lacunae filled with maternal blood Maternal diet is the source of the nutrients supplied to the fetus If mother is fasting : glucose is released from glycogen but storage is not adequate Cleavage of triacylglycerols (stored in adipose tissue) provide the mother with energy in the form of free fatty acid Glucose Facilitated diffusion A major nutrient for growth and energy of the fetus hPL : blocking the peripheral uptake and utilization of glucose by maternal tissue while promoting the mobilization and utilization of free fatty acid Lactate Transports across the placenta by facilitated diffusion Co-transport with hydrogen ion : lactate is probably transported as lactic acid Beware of lactic acidosis Free fatty acid and triglycerides Neutral fat (triglycerides) does not cross the placenta Glycerol : cross the placenta The apoprotein and cholesterol esters of LDL are hydrolyzed by lysosomal enzymes in trophoblasts : and give Cholesterol for progesterone synthesis Free amino acids (including essential amino acids) Essential fatty acid Amino acid By the use of LDL Also directly cross the placenta by diffusion Proteins and other large molecules Larger proteins (ie albumin) : limited transfer across the placenta Globulin (IgG) cross the placenta in major amounts IgM : increased amount is found only fetal infection in utero Iron and trace elements Active transport Clinical correlations Iron : active transport ; maternal iron deficiency anemia if no additional intake ; it is recommended to supplement iron in pregnancy with total 1000 mg throughout pregnancy (absorbed form) or 6-7 mg/d (absorbed form) or 30-60 mg/d (elemental form) in singleton pregnancy IgM : indicated fetal infection Risk of lactic acidosis : becareful in giving any drugs to pregnant women Risk of maternal DM and fetal macrosomia : hPL (human placental lactogen), glucagon, insulinase / glucose transport is easily by facilitated diffusion Physiological aspect and clinical correlation Fetal physiology mostly not the same as the newborn and moreover , the human adult Fetal circulation Three major shunts Ductus venosus Foramen ovale Ductus arteriosus All nutrient materials deliver from placenta to fetus via umbilical vein Single umbilical vein carries oxygenated , nutrient bearing blood IVC consists of an admixture of arterial likeblood (more oxygenation than SVC) IVC blood to heart then directly through foramen ovale into left atrium Then into left ventricle then eject to 2 vital structures : the heart and the brain Bypass pulmonary circulation Venous blood from SVC : into right ventricle then to pulmonary trunk and through ductus arteriosus into the descending aorta Clinical correlation Umbilical cord : 2 arteries / 1 vein ; abnormality can be detected such as single umbilical artery and associated with fetal KUB anomaly After birth: the umbilical vessels, ductus arteriosus, foramen ovale, ductus venosus normally constrict Cord clamp and expansion of lung and breathing : induce constriction PDA (patent ductus arteriosus) is common Umbilical vein : ligamentum teres Ductus venosus : ligamentum venosum Fetal blood Hematopoiesis is demonstrable first in yolk sac The next major site of erythropoiesis is liver The final site : bone marrow The fetoplacental blood volume at term = 120 mg/kg of infant weight Clinical correlation Embryonic hemoglobin = Gower 1 (€2/r2) and Gower 2 (€2/α2) Fetal hemoglobin = Hb F (α2/r2) β thalassemia : no symptoms in utero but symptoms will be present after birth due to lack of Hb A (α2/β2) Respiratory system Fetal breathing : enhance expansion of the lung, distended alveoli, and promote surfactant secretion Pneumocyte type 2 : surfactant secretion Surfactant excrete into amniotic fluid Clinical correlation Oligohydramnios : lung hypoplasia Lung maturity testing : amniotic fluid (from amniocentesis) for shake test, L:S ratio, phosphatidylglecerol level Respiratory distress syndrome (RDS) found more commonly in preterm birth due to surface inadequacy Conclusion To know embryology : to understand “why” the infants are in trouble and “how” to treat them Clinical correlation in practice has related to morphological/ biochemical/ physiological aspects in fetal development Thank you for your attention