Fetal Growth and Development PDF

Reproductive System Lecture 1 & 2 Fetal Physiology, Growth & Development  Objectives By the end of this session you should be able to: Define the fetal period Describe the pattern of increase of fetal size, weight & body proportion during pregnancy...

Reproductive System Lecture 1 & 2 Fetal Physiology, Growth & Development  Objectives By the end of this session you should be able to: Define the fetal period Describe the pattern of increase of fetal size, weight & body proportion during pregnancy Describe the important events in the development of each of the major body systems Describe the factors which influence the viability of the pre-term neonate Describe the effects on the fetus of poor nutrition during early & late pregnancy Describe the function of the fetal kidneys Describe the processes involved in the control of amniotic fluid volume & composition Describe the fetal circulation & the changes which occur at birth Describe oxygen transport in fetal blood  Crown-Rump Length (CRL) is a measurement commonly used in obstetrics during the rst trimester of pregnancy to estimate the Pre-Embryonic Period : Fertilisation 3 weeks gestational age of a fetus. It refers to the Embryonic Period: 3 8 weeks distance from the top of the fetus’s head (crown) to the bottom of the torso (rump), excluding the Fetal Period: 8 38 weeks legs.  Describe the pattern of increase of fetal size, weight and body proportion during pregnancy Growth and weight gain accelerate during pregnancy. Crown Rump Length (CRL) increases rapidly in the pre-embryonic, embryonic and early fetal periods. Weight gain is slow at first, but increases rapidly in the mid and late fetal periods. o Embryo Intense morphogenesis and differentiation Little weight gain Placental growth most significant o Early fetus Protein deposition o Late fetus Adipose deposition Body Proportion Body proportions change dramatically during the fetal period. o At week 9, the head is approximately half of the crown rump length-CRL (A) o Thereafter, body length and lower limb growth accelerates. o At birth the head is approximately one quarter of the crown heel length - CHL (B, C) Fetal Growth The failure of the fetus to reach its full growth potential ( weight is below the 10th percentile for gestational age) is regarded as having ‘fetal growth restriction’ FGI o Symmetrical Growth Restriction Growth restriction is generalised and proportional o Asymmetrical Growth Restriction Abdominal growth lags Relative sparing of head growth Tends to occur with deprivation of nutritional and oxygen supply to fetus Depending on the cause a fetus with IUGRintraUterinegrowthrestriction may be compromised in the uterine environment & require closer monitoring in order to allow the continuation of the pregnancy to term. Q: Explain why growth restricted and premature infants are prone to neonatal hypoglycemia ??? The factors that predispose these patients to hypoglycaemia include failure of counter-regulation, immaturity of the enzyme systems regulating glycogenolysis, gluconeogenesis, ketogenesis, reduced adipose tissue stores, hyperinsulinism or increased sensitivity to insulin.  seduce a The important events in the development of each of the major body systems The lungs develop relativ e ly l a t e , a s R e s p i r a to ry System they are not needed until birth. o Embryonic development creates only the bronchopulmonary tree Airways, no gas exchanging parts o Functional specialisation occurs in the fetal period o Major implications for pre-term survival Threshold of Viability Viability is only a possibility after 24 weeks pseudoglandalestage II  Terminysacstate 8 5 state 28 Te beforesweekembryon stage Pseudoglandular Stage Weeks 8 – 16 Duct systems begin to form within the bronchopulmonary segments created during the embryonic period Terminal-Bronchioles  vascularformation Canalicular Stage t Weeks 16 – 26 Formation of respiratory bronchioles o – Budding from bronchioles formed during the pseudoglandular stage May be viable at the end More vascular Some terminal sacs Terminal Sac Stage o Week 26 – Term o Terminal sacs begin to bud from the respiratory bronchioles o Some primitive alveoli o Differentiation of pneumocytes Type 1 – Gas exchange Type 2 – Surfactant production from week 20 Surfactant EE It is a mixture of phospholipids and protein E i Alveoli Dreams 2 jan Surfactant prevents the collapse of small alveoli during expiration by lowering surface tension Inadequate amounts of surfactant result in poor lung expansion and poor gas exchange (e.g in infants delivering preterm, prior to the maturation of the surfactant system, this results in a condition known as respiratory distress syndrome=RDS). preventcollapse of small alveoliduringexpiration bD fartergun howering su The production of surfactant is enhanced by: - cortisol, - growth restriction and - prolonged rupture membranes, & is delayed in diabetes.  periedm alveoliContainfluid alveola Alveolar Period o Late fetal 95% of Alveoli are formed post-natally During T2 and T3 gas exchange occurs at the placenta. However, the lungs must be prepared to assume the full burden immediately after birth. o ‘Breathing’ movement Conditioning of the respiratory musculature o Fluid filled Crucial for normal lung development Earth FBW  camn.ufc Numerous, but intermittent, fetal breathing movements occur in utero, and along with an adequate amniotic fluid volume appear to be necessary for lung maturation. hypipbgia oligohgloam G se - Oligohydramnios (reduced amniotic fluid volume), - Decreased intrathoracic space (e.g. diaphragmatic hernia or chest wall deformities) can result in pulmonary hypoplasia, which leads to progressive respiratory failure from birth. FBMs, amniotic uid, and thoracic space are indispensable for fetal lung development. Disruptions in any of these factors can lead to pulmonary hypoplasia, signi cantly a ecting neonatal respiratory function. Early detection and management strategies are crucial to improve outcomes.  Nervous System O The nervous system is the first to begin development and the last to finish. o Corticospinal tracts required for coordinated voluntary E movements begin to form in the 4th month o Myelination of the brain only beings in the 9th month Corticospinal tract myelination incomplete at birth, as evidence by increased infant mobility in the 1st year o No movement until Week 8 o o After week 8 a large repertoire of movements develop ‘Practicing’ for post-natal life E.g. suckling, breathing  Nervous System 82 The brain is the fastest developing organ in the fetus and infant. On average it accounts for 12% of body weight at birth, falling to about 2% in adults. During the fetal period important changes occur, structurally and functionally. o Cerebral hemisphere becomes the largest part of the brain 00 Gyri and sulci form after 5 months as the brain consists of many layers that grow at different rates. o Histological differentiation of cortex in the cerebrum and cerebellum o Formation and myelination of nuclei and tracts o Relative growth of the spinal cord and vertebral column b a 66 week  Fetal movement 0 o Fetal movements can be seen by USS at Week 8 8 o Quickening : First maternal awareness of fetal movements 18 -20 Wks in primiparae and 2 Wks earlier in multiparae e o Low cost, simple method of ante-partum fetal surveillance o Reveals fetuses that require follow-up  Sensory and Motor Systems Hearing and taste mature before vision. The organ of corti in the inner ear is well developed in the fetus at 5 months, c 20mn O_0 but the retina is immature at birth.  O Describe the factors which influence the viability of the pre term neonate- o Threshold of Viability Viability is only a possibility once the lungs have entered the terminal sac stage of development (after 24 weeks). O Brain Development Viability is only possible if the brain is sufficiently mature to control body functions, e.g. breathing. o Respiratory Distress Syndrome o Often affects infants born prematurely o Insufficient surfactant production o If pre-term delivery is unavoidable or inevitable Glucocorticoid treatment (of the mother) increases surfactant 80 production in the fetus Exogenous surfactant may also be given postnatally.  Urinary System Kidneys o Ascent of kidneys complete at week 10 o Fetal kidney function begins in week 10 m Functional embryonic kidney is the Metanephros (ureter, pelvis, calyces and collecting ducts) o Renal pelvis, calyces etc present by week 23 o Histological differentiation of cortex and medulla almost complete by 8 months a o 0 Nephrogenesis is complete by 36 weeks The functional embryonic kidney is the Metanephros, which produces Fetal Urine. m3omtlh adult o Fetal urine is a major contributor to amniotic fluid volume o At 25 weeks the fetus produces ~100ml of hypotonic urine a day 0 o Fetal urine production rises gradualy from about 12 ml / h at 32 weeks gestation to 38 ml / h (~500ml of urine a day) at term Adults only produce ~1 Litre a day! o Fetal kidney function is not necessary for survival during pregnancy, but without it there is oligohydramnios.  Urinary System Bladder o Lies in the abdominal cavity in the fetus and infant o Urine is emptied into the amniotic fluid, to be swallowed by the fetus. o Bladder fills and empties every 40 – 60 minutes in the fetus (seen on USS)  Gastrointestinal system o The primitive gut is present by the end of fourth week o Fetus swallows amniotic fluid constantly o Perstalsis in the intestine occurs from the second trimester don'tproducemeconium Absorbs water and electrolytes Debris accumulates in fetal gut Together with gut debris forms Meconium. The large bowel is full with meconium at term  Defecation in utero,and hence meconium in the amniotic fluid, is associated with post- term pregnancy and fetal hypoxia It is postulated that fetal hypoxia leads to an Explain why increased output by the vagus, stimulating the fetal gut and resulting in the passage of ?? meconium. Aspiration of meconium-stained liqour by the fetus at birth can result in meconium aspiration syndrom and respratory distress This aspiration induces hypoxia via Explain why ?? four major pulmonary effects: airway obstruction, hypertension. surfactant dysfunction, chemical pneumonitis, and pulmonary  obstruction airway surfactant d fut Bilirubin 815rem o Formed as a result of Haemoglobin breakdown in the fetus and mother o Mother excretes bilirubin via bile Must be conjugated first 0 o 8 Fetus cannot conjugate bilirubin because of relative deficiencies of necessary enzymes such as glucoronyle transferase The unconjugated bilirubin crosses placenta (after accumulating – active transport from the fetus to the mother) Excreted by mother o Neonate may become jaundiced (transient unconjugated hyperbilirubinemia or physiological jaundice) if conjugation does not establish quickly particulerly in premature infant Liver has never had to conjugate bilirubin before during pregnancy, so it takes a little bit of time for the liver to kick in The loss placental excretion of unconjugated bilirubin Photo-oxidation adds oxygen to the bilirubin so it dissolves easily in water. This makes it easier for liver to break down and remove the bilirubin from their blood. Exposure to light (phototherapy) stimulates the liver to begin conjugation Describe the processes involved in the control of amniotic fluid volume and composition Amniotic Fluid Amniotic fluid surrounds the fetus, and is turned over constantly. o Early in pregnancy Formed from maternal fluids Initially secreted by the amnion By week 10 it is mainly a transudate of the fetal serum (Fetal extracellular fluid by diffusion across non-keratinised skin) o Later in pregnancy Turnover via fetus ( fluid through the kidney and lung fluid and removal by fetal swallowing) Amniotic fluid volume increases progressively ~10ml at 8 weeks (10 weeks: 30 mL; 20 weeks: 300 mL; 30 weeks: 600 mL; 38 weeks:1000 mL), but from term there is a rapid fall in volume (40 weeks: 800 mL; 42 Yaml weeks: 300- 350 mL).  The function of the amniotic fluid is to : -providing mechanical protection (shock absorber) -a moist environment so the fetus does not dehydrates -Maintaining a relatively constant temperature for the environment surrounding the fetus, thus protecting the fetus from heat loss - permit movement of the fetus while preventing limb contracture; - prevent adhesions between fetus and amnion; - permit fetal lung development if  Amniotic fluid contains cells from the fetus and amnion. It included a variety of proteins, and if sampled via a Amniocentesis, can be diagnostically useful. In what conditions??? c Amniocentesis is US guided, the physician will insert syringe & take sample from amniotic sac for diagnosis of many condition  Cardiovascular System The fetal cardiovascular system is arranged to ensure oxygenated blood collected by the umbilical vein at the placenta is circulated around the fetus.  Describe the fetal circulation and the changes which occur at birth Before Birth: o Oxygenated blood enters fetus via the Umbilical Vein from the placenta o Oxygenated blood bypasses the liver via the Ductus Venosus o O Oxygenated blood passes from the RA LA via the Foramen Ovale o Blood passes from the pulmonary artery Aorta via the Ductus o Arteriosus o Deoxygenated blood returns to the placenta via the two Umbilical Arteries o Resistance in the lungs is extremely high, due to Hypoxic Pulmonary E Vasoconstriction. https://www.youtube.com/watch?feature=player_embedded&v=-IRkisEtzsk Before th RSL 918  AfterB I LYR 42Resistance The infant takes its first breath, removal After Birth Hypoxic Pulmonary Vasoconstriction and greatly reducing the resistance of the lungs. o Greater venous return to LA Pressure in LA > RA Closure of the Foramen Ovale (Minutes) o Increased O 2 saturation of blood and decreased [Prostaglandins] (placenta has been removed) Constriction of Ductus Arteriosus Constriction of Umbilical Artery (Hours) o Stasis of blood in Umbilical Vein and Ductus Venosus Clotting of blood Closure due to subsequent fibrosis (Days) https://www.youtube.com/watch?v=jFn0dyU5wUw&feature=player_embedded  CO2 Transfer Transfer of CO2 is also dependent on partial pressure gradients. However, the fetus cannot tolerate higher pCO2 than the mother due to acid base problems. Transfer of CO2 therefore needs to be facilitated by lowering maternal pCO2. This is achieved by Hyperventilation, stimulated by Progesterone. Thank you Fetal Growth and Development  Estimation of Gestational Age It is important to distinguish between a fetus born prematurely and one born full term but small. Age may be estimated by a range of methods: Duration of Pregnancy o Fertilisation age (conceptional age) ▪ Use of calendar months may cause inaccuracies o Age since mother’s Last Menstrual Period (LMP) ▪ Irregular cycles may cause confusion The median duration of pregnancy is 280 days (40 weeks) and this gives the estimated date of delivery (EDD). Nagel role Amca IE The EDD is calculated by taking the date of the LMP, counting forward by nine months or backward by 3 months and adding 7 days Prerequisites: Joji 569m The cycle length is 28 days (ovulation at day14); The cycle was a normal cycle (i.e. not straight afterstopping the oral contraceptive pill or soon after a previous pregnancy). In most antenatal clinics, there are pregnancy calculators (wheels) that do this for you LMP: January 1 Define Add 7 days: January 8 Count forward 9 months: October 8 -term, Thus, the EDD is October 8. -preterm, This method provides an approximation and is -post-term & often supplemented by clinical and ultrasonographic evaluations. -postdate? Dating the pregnancy  Cfundai symphysis Symphysis – Fundal height o(SFH) Distance between symphysis pubis to top 0 of uterus (fundus) o Measured with a tape measure conf Sf Gase o Variation occur with: f ▪ Number of fetuses ▪ Volume of amniotic fluid ▪ The lie of the fetus. ▪ Engagement of head, What are the causes of small-for- date fundal height & large-for- date fundal height?  U/S in Obstetrics The gestational sac 4–5 wks The embryo can be observed & measured at 5–6 wks Trans-abdominal probe about 6 wks. A visible heartbeat Transvaginal U/S 1 wk earlier than transabdominal U/S Timing: CRL is early (6–14 weeks), while CHL, BPD, and FL are later (14+ weeks). SFH is external and used after 20 weeks. Purpose: CRL is for gestational age estimation. BPD and FL help in growth assessment and fetal weight estimation. SFH is for quick external monitoring. Measurement Technique: CRL, CHL, BPD, and FL are ultrasound-based. SFH is done manually with a tape measure. Each measurement provides unique insights into fetal development at specific stages of pregnancy. Trans-vagina l Developmental criteria o Crown-Rump length (CRL ) ▪ Used in T1 o Biparietal diameter of head (BPD) o Femur length (FL) ▪ BPD & FL used in T2/T3 o Weight after delivery o Appearance after delivery What is the accuracy of prediction of GA by -CRL at T1? Gestational age -BPD at 20 wk? Which is one of them is more accurate in dating Gestational sac BPD FL In the latter part of pregnancy, measuring fetal abdominal circumference forfastergrowth (AC) & HC will HC assessmentof allow the growth of the fetus size and& will assist in the diagnosis and management of IUGR. These 2 measurements are not usually used for dating pregnancy. Abdominalcircumference AC AC Headcircumference HC  Techniques used to Assess Fetal growth & oDevelopment Fetal movements kick chart o Ultrasound Scan o Doppler ultrasound o Non-Stress Tests (NST) ▪ Monitors fetal heart-rate changes associated with fetal movement o Vibroaccoustic stimulation o Contraction stress test (Monitors fetal heart-rate changes associated with uterine contractions.) o Biophysical profiles (BPP) ▪ 5 measured variables Amniotic Fluid Volume Oligohydramnios89 Respiratory distress Too little unexplained Placental insufficiency Fetal renal impairment Pre-eclampsia syndrome.io Polyhydramnois Too much unexplained Fetal abnormality oE.g. inability to swallow oStructural – blind-ended oesophagus oNeurological – unable to coordinate swallowing movements Examination of the fetal heart A Doppler ultrasound device (Sonicaid) from about 12 weeks A fetal stethoscope (Pinard) from about 24 weeks gestation The fetal heart is best heard at the anterior shoulder of the fetus Fetal bradycardia is associated with fetal distress and may end in fetal demise  Cardiotocograph Baseline rate; The normal fetal heart rate at term is 110–150 bpm. Baseline y variability; is considered abnormal when it is less than 10 beats per minute (bpm) Accelerations; These are increases in the baseline fetal heart rate of at least 15 bpm, lasting for at least 15 seconds. The presence of two or more accelerations on a 20–30-minute CTG defines a reactive trace and is indicative of a non-hypoxic fetus, i.e. they are a positive sign of fetal health. Decelerations; These are transient reductions in fetal heart rate of 15 bpm or more, lasting for more than 15 seconds. Decelerations can be indicative of fetal hypoxia or umbilical cord compression. 1ham.ing  Classification of Birth Weights smallGestational age o < 2,500g = SGA or IUGR o 2,500- 3,500g = Average or AGA o > 4,500g = LGA or Macrosomia hurgetastational Ase What are the causes of macosomia? prior macrosomic infant, maternal prepregnancy weight, excessive gestational weight gain, multiparity, male fetus, gestational age >40 weeks, ethnicity, maternal birth weight, maternal height, maternal age younger than 17 years, and a positive 50g glucose screen with a normal 100g glucose tolerance test,  Describe the effects on the fetus of poor nutrition during early and late pregnancy Poor Nutrition in Early Pregnancy o Neural tube defects ▪ E.g. DiGeorge Syndrome ▪ Anencephaly and spina bifida Poor Nutrition in Late Pregnancy o Asymmetrical Growth Restriction ▪ Subsequent oligohydramnios FETAL GROWTH AND DEVELOPMENT Dr. Safinaz Abubakir Obstetrician and gynecologist Learning objectives Understand that fetal growth and birth weight are important determinant of immediate neonatal health and long term adult health. Appreciate the fetal ,maternal ,placental factor that effect fetal growth and development. Be familiar with fetal circulation. Be aware of normal fetal organ development during pregnancy. Recognize the importance the normal amniotic fluid physiology to fetal growth and development. Introduction Over view… Development ,growth and maturation of the main body organ and system in human fetus and implication of disordered growth. Knowledge of normal development ,growth and maturation is important for understanding the complication that may arise in pregnancy and for the neonate ,foe example understanding of normal lung development will explain why preterm infant are at higher risk of respiratory distress syndrome than term infant. Fetal growth Fetal growth and the weight of the fetus at birth are important not only for the immediate health of the neonate but also for the long-term health of the adult, and even into the next generation. Fetal size can be assessed antenatally in two ways, either externally by using a tape measure to assess the uterine size from the superior edge of the pubic symphysis to the uterine fundus (symphysis–fundal height [SFH]) or using ultrasound to measure specific parts of the fetus and then calculating the estimated fetal weight (EFW). The fetal size is described in terms of its size for gestational age and is presented on centile charts.Obstetric history and examination, that take into consideration factors that are known to affect fetal growth such as maternal height, weight, parity, ethnicity and fetal sex. A fetus that is less than the 10th centile is described as being small for gestational age (SGA). An SGA fetus may be constitutionally small. Many fetuses that are SGA ,however,have failed to reach their full growth potential, a condition called fetal growth restriction (FGR). FGR is associated with a significant increased risk of perinatal morbidity and mortality. Growth-restricted fetuses are more likely to suffer intrauterine hypoxia/asphyxia and, as a consequence, be stillborn or demonstrate signs and symptoms of hypoxic-ischaemic encephalopathy (HIE), including seizures and multiorgan damage or failure in the neonatal period. Other complications to which these growth-restricted babies are more prone include neonatal hypothermia, hypoglycaemia, infection and necrotizing enterocolitis. cerebral palsy is more prevalent and low birthweight infants defined as Efwt < 2500 gm) and SGA baby are more likely to develop hypertension, cardiovascular disease (ischaemic heart disease and stroke) and diabetes in adult life, indicating that the impact of FGR is long lasting. Interventions to deliver the growth-restricted fetuses early from the intrauterine environment may improve outcome. It is important to note that not all growth-restricted fetuses are SGA, although a baby's birthweight is within the normal range for gestation (above the 10th centile) they may have failed to reach their full growth potential. Detecting these fetuses is even more difficult than identifying the small growth-restricted fetus. Figure 1 Population centile chart for estimated fetal weight by ultrasound measurements. Fetus (A) has normal growth( green crosses); fetus (B) has suboptimal growth (red crosses). Determinants of fetal growth and birthweight Determinants of fetal growth and birthweight are multifactorial. They include the influence of the natural growth potential of the fetus, which is dictated largely by the fetal genome and epigenome , but also the intrauterine o environment, which is influenced by both maternal and placental factor.The birthweight is therefore the result of the interaction between the fetus and the maternal uterine environment. Fetal growth is dependent on adequate delivery to, and transfer of nutrients and oxygen across, the placenta, which relies on appropriate maternal nutrition and placental perfusion. Other factors are important in determining fetal growth and include, fetal hormones that affect the metabolic rate, growth of tissues and maturation of individual organs. In particular, insulin like growth factors (IGFs) coordinate a precise and orderely increase in growth throughout late gestation. Insulin and thyroxin (T4) are required through late gestation to ensure appropriate growth in normal and adverse nutritional circumstances. Fetal hyperinsulinaemia, which occurs in association with maternal diabetes mellitus when maternal glycaemic control is suboptimal, results in fetal macrosomia with in particular excessive fat deposition. This leads to complications such as late stillbirth, shoulder dystocia and neonatal child hypoglycaemia. Difficult birth Fetal influences Genetic : 25 fetal genome plays a significant role in determining fetal size. Early onset and sometimes severe FGR is seen in fetuses with chromosomal defects such as the trisomies, particularly of chromosomes 13 (Patau’s syndrome) and 18 (Edward’s syndrome) as well as triploidy. FGR is also common in trisomy 21 (Down’s syndrome). The other genetic influence is fetal sex with slightly greater birth weights in males. Epigenetic : epigenetic changes plays a role in determining fetal size. Epigenetic changes are modification of DNA ,which occur without any alteration in the underlying DNA sequence ,and can control wheather a gene is turned on or off and how much of particular message is made.In Genomic imprinting ,the epigenetic process silences one parental allele, resulting in monoallelic expression. genes that are paternally expressed promote fetal growth, whereas maternally expressed genes suppress growth. Infection : Infection has been implicated in FGR, particularly rubella, cytomegalovirus, Toxoplasma and syphilis. When a fetus is found to be very small on ultrasound measurement (for example EFW less than the 5th centile for gestational age) it is common to test the maternal blood for antibodies to these infections. The results are then compared with samples taken at booking to  he results are then compared with samples taken at booking to determine if the mother has evidence of seroconversion during pregnancy, which would suggest an acute infection. 1 forinfection Maternal influences IgMantibody Physiological influences : in normal pregnancy maternal physiological influences on birth weight include: Maternal height, prepregnancy weight, age and ethnic group. Heavier and taller mothers tend to have bigger babies and certain ethnic groups have lighter babies (e.g. South Asian and Afro-Caribbean). Parity is also has influence with increasing parity being associated with increased birthweight. Age influences relate to the association with age and parity (i.e. older mothers are more likely to be parous). Teenage pregnancy is also associated with FGR. In older women the increased risk of chromosomal abnormalities and acquired maternal disease, for example hypertension, lead to lower birthweights. Behavioural : Smoking, alcohol and recreational drug use all associated with reduced fetal growth and birthweight. Babies born to mothers who smoke during pregnancy deliver babies up to 300 g lighter than non-smoking mothers. This effect may be Feel through toxins carbon monoxide, or vascular effects on the uteroplacental circulation. Stopping smoking even through pregnancy, can lead to increased birthweight. Alcohol crosses the placenta and a dose-related effect has been noted, with up to 500 g reduction in birthweight, along with other anomalies occurring in women who drink heavily (two drinks per day), such as developmental delay. The use of recreational drugs is often associated with smoking and alcohol use but there is evidence to suggest that heroin is independently associated with a reduction in birthweight. Cocaine use is associated with spontaneous preterm birth, low birthweight and small head circumference. Placental abruption is associated with cigarette smoking and use of recreational drugs such as cocaine. Chronic disease Chronic maternal disease may restrict fetal growth. Such diseases are largely those that affect placental function or result in maternal hypoxia. Conditions include hypertension (essential or secondary to renal disease) and lung or cardiac conditions (cystic fibrosis, cyanotic heart disease). Hypertension can lead to placental infarction that impairs its function. Maternal thrombophilia can also result in placental thrombosis and infarction. Placental influences Normal placental development and function from early pregnancy is key to ensuring that the fetus receives adequate oxygen and nutrients from the mother. Placental insufficiency occurs when there is inadequate transfer of nutrients and oxygen across the placenta to the fetus. It can be due to poor maternal uterine artery blood flow, a thicker placental trophoblast barrier and/or abnormal fetus villous development. Placental infarction secondary to the maternal chronic conditions or acute premature separation as in placental abruption can impair this transfer and hence fetal growth. Recurrent bleeding from the placenta (antepartum haemorrhage) can, over time, compromise placental function, leading to poor fetal growth in the latter part of pregnancy. poor uteratblooton Improblest bam thickplane abon_ Fetal development 1 Ebook Cardiovascular system and the fetal circulation The fetal circulation is quite different from that of the adult (Figure 2). The fetal circulation is characterized by four shunts that ensure that the oxygenated blood from the placenta is prioritized for delivery to the fetal brain. These shunts are the: Umbilical circulation Ductus venosus. Foramen ovale. Ductus arteriosus. The umbilical circulation carries fetal blood to and from the placenta for gas and nutrient exchange. The umbilical arteries arise from the caudal end of the dorsal fetal aorta and carry deoxygenated blood from the fetus to the placenta. Normally two umbilical arteries are present, but a single umbilical artery in approximately 0.5% of fetuses and can be associated with reduced fetal growth velocity and some congenital anomalies. Oxygenated blood is returned to the fetus via the umbilical vein to the fetal liver. A small proportion of blood oxygenates the liver but the bulk passes through the ductus venosus bypassing the liver and joins the inferior vena cava (IVC) as it enters the right atrium. The ductus venosus is a narrow vessel and high blood velocities are generated within it. This streaming of the ductus venosus blood, together with a membranous valve in the right atrium (the crista dividens), prevents mixing of the well-oxygenated blood from the ductus venosus with the desaturated blood of the The ductus venosus stream passes across the right atrium through foramen ovale, to the left atrium. From here, the blood passes through the mitral valve to the left ventricle and hence to the aorta. About 50% of the blood goes to the head and upper extremities, providing high levels of oxygen to supply the fetal heart, upper thorax and brain; the remainder passes down the aorta to mix with blood of reduced oxygen saturation from the right ventricle. Deoxygenated blood returning from the fetal head and lower body flows through the right atrium and ventricle and into the pulmonary artery, after which it bypasses the lungs to enter the descending aorta via the ductus arteriosus that connects the two vessels. Only a small portion of blood from the right ventricle passes to the lungs, as they are not functional. This means, the desaturated blood from the right ventricle passes down the aorta to enter the umbilical arterial circulation and be returned to the placenta for reoxygenation. Prior to birth, the ductus a ateriosus remains patent due to the production of prostaglandin E2 and prostacyclin, which act as local vasodilators.  nonsteroidal Ud 4,04 Premature closure of the ductus arteriosus has been reported with the administration of cyclooxygenase inhibitors before birth. At birth, the cessation of umbilical blood flow causes cessation of flow in the ductus venosus, a fall in pressure in the right atrium and closure of the foramen ovale. Ventilation of the lungs opens the pulmonary circulation, with a rapid fall in pulmonary vascular at resistance, which dramatically increases the pulmonary circulation. The ductus arteriosus closes functionally within a few days of birth. Occasionally ,this transition from fetal to adult circulation is delayed,usually because pulmonary vascular resistance fail to fall despite adequate breathing war.this delay, termed persistant fetal circulation ,result in left to right shunting of blood from the aorta through the ductus arteriosus to the lung ,the baby become cyanosed and can suffer from life threateining hypoxia ,this delay in closure of ductus arteriosus commonly seen in infant born preterm < 37 weeks gestation.it result in congestion in pulmonary circulation and reduction in blood flow to GIT and brain and implicated in pathogenesis of necrotisisng fasciitis and intraventricular hemorrhage ,both of which are complication of preterm birth. The closure of fetal cardiac shunts after birth is a critical physiological transition as the newborn shifts from fetal circulation to independent pulmonary circulation. Here is the sequence: 1. Umbilical Cord Clamping Once the umbilical cord is clamped, placental blood flow stops. This increases systemic vascular resistance, raising left atrial pressure. 2. Lung Expansion The newborn’s first breaths expand the lungs, decreasing pulmonary vascular resistance and increasing pulmonary blood flow. Oxygen levels rise, further reducing pulmonary resistance. 3. Functional Closure of the Foramen Ovale The increased left atrial pressure (due to increased pulmonary venous return) and decreased right atrial pressure (due to reduced venous return from the placenta and decreased pulmonary vascular resistance) cause the foramen ovale’s flap to close. This typically happens within minutes to hours after birth. 4. Closure of the Ductus Arteriosus Rising oxygen levels and decreased prostaglandins (no longer produced by the placenta) cause the ductus arteriosus to constrict. Functional closure usually occurs within 12–24 hours after birth, with permanent anatomical closure occurring within a few weeks. 5. Closure of the Ductus Venosus The ductus venosus, which bypassed the liver in fetal circulation, constricts and closes over a few days. Blood now flows through the liver. 6. Adaptation of Circulatory System The heart and vascular system adapt fully to the new circulatory pattern, ensuring oxygenated blood from the lungs is pumped to the body and deoxygenated blood returns to the lungs. Timeline Overview: Minutes to Hours: Foramen ovale closes functionally. 12–24 Hours: Ductus arteriosus closes functionally. Days: Ductus venosus closes. Weeks: Permanent anatomical closure of ductus arteriosus and foramen ovale. If these shunts fail to close properly, conditions such as patent ductus arteriosus (PDA) or atrial septal defect (ASD) can occur. Figure 2 Diagrammatic representation of fetal circulation. foramoroval min Ductalask.io h DuctusVenosa day Organ 558ha Heart 944 Central nervous system Neural development is one of the earliest systems to begin and one of the last to be completed during pregnancy, generating the most complex structure within the fetus. The early central nervous system (CNS) begins as a simple neural plate that folds to form a groove then tube, open initially at each end. Failure of these opening to close contributes a major class of neural abnormalities called neural tube defects (NTDs).there is a rapid increase in total grey matter in the last trimester, which is mainly due to four fold increase in cortical grey matter.  ectoderm Derivative of mesoder endoderm Respiratory system: The lung first appears as an outgrowth from the primitive foregut at about 3–4 weeks postconception and by 4–7 weeks epithelial tube branches and vascular connections are forming. By 20 weeks the conductive airway tree and parallel vascular tree is well developed. By 26 weeks with further development of the airway and vascular tree,the type I and II epithelial cells are beginning to differentiate. Pulmonary surfactant, a complex mixture of phospholipids and proteins that reduces surface tension at the air–liquid interface of the alveolus is produced by the type II cells starting from about 30 weeks. Dilatation of the gas exchanging airspaces,alveolar formation and maturation of the surfactant system continues between this time and delivery at term. The fetal lung is filled with fluid, the production of which starts in early gestation and ends in the early stages of labour. At birth, the production of this fluid ceases and the fluid present is absorbed. Adrenaline, to which the pulmonary epithelium becomes increasingly sensitive towards term, appears to play a major role in this process. With the clearance of the fluid and with the onset of breathing, the resistance in the vascular bed falls and results in an increase in pulmonary blood flow. A consequent increased pressure in the left atrium leads to closure of the foramen ovale. Pulmonary surfactant prevents the collapse of small alveoli during expiration by lowering surface tension. The predominant phospholipid in surfactant (80% of the total) is phosphatidylcholine (lecithin), the production of which is 0 enhanced by cortisol, growth restriction and prolonged rupture of the membranes, and is delayed in maternal diabetes mellitus.  Inadequate amounts of surfactant result in poor lung expansion and poor gas exchange. In infants delivering preterm, prior to the maturation of the surfactant system, this results in a condition known as respiratory distress syndrome (RDS). It typically presents within the first few hours of life with signs of respiratory distress, including tachypnoea and cyanosis. It occur in more than 80% of infant born between 23-27 weeks ,falling to 10% of infant born between 34-36 weeks gestation. Acute complication include ,hypoxia ,asphyxia f ,intraventricular hemorrhage ,necrotizing enterocolitis. The incidence and severity of RDS can be reduced by administering steroids antenatally 12-24 hours before they deliver preterm to mothers at risk of preterm delivery. The steroids cross the placenta and stimulate the premature release of stored fetal pulmonary surfactant in the fetal alveoli..fetal breathing movement (FBM)help to maintain high level of lung expansion that’s essential for lung maturation and development.prolong abscense of FBM is likely to reduce lung expansion that lead to hypoplasia of the lung. An adequate amniotic fluid volume is also necessary for normal lung maturation.. Oligohydramnios (reduced amniotic fluid volume), decreased intrathoracic space (e.g. diaphragmatic hernia) or chest wall deformities can result in pulmonary hypoplasia, which leads to progressive respiratory failure from birth. Cause of pulmonary hypoplasia 1.Reduced or absent fetal movement Inherited neuromuscular development 2.Reduced amniotic fluid or absent amniotic fluid preterm pre labor rupture membrane bilateral congenital renal agenesis 3.Decrease intrathoracic space congenital diaphragmatic hernia congenital malformation of lung skeletal dysplasia Alimentary system The primitive gut is present by the end of the fourth week, having been formed by folding of the embryo in both craniocaudal and lateral directions, with the resulting inclusion of the dorsal aspect of the yolk sac into the intraembryonic coelom. The primitive gut consists of three parts, the foregut, midgut and hindgut, and is suspended by a mesentery through which the blood supply, lymphatics and nerves reach the gut parenchyma. The foregut endoderm gives rise to the oesophagus, stomach, proximal half of the duodenum, liver and pancreas. The midgut endoderm É gives rise to the distal half of the duodenum, jejunum, ileum, caecum, appendix, ascending colon and the transverse colon. The hindgut endoderm develops into the descending colon, sigmoid colon and the rectum. Between 5 and 6 weeks, probably due to the lack of space in the abdominal cavity as a consequence of the rapidly enlarging liver and elongation of the intestine, the midgut is extruded into the umbilical cord as a physiological hernia. The gut undergoes a 270 anticlockwise rotation prior to re entering the abdominal cavity by 12 weeks of gestation. Failure of the gut to re-enter the abdominal cavity results in the development of an omphalocele and this condition is associated with chromosomal anomaly (Figure 3). Other malformations include those that result from failure of the normal rotation of the gut, fistulae and atresias. As the fetus continually swallows amniotic fluid, any obstruction that prevents fetal swallowing or passage of amniotic fluid along the gut will result in the development of polyhydramnios (excess amniotic fluid). Gastrointestinal fistulae can also occur, the most common being a tracheo-oesophageal fistula (TOF) (Figure 4), in which a connection exists between the distal end of the oesophagus and the trachea. Without surgical intervention the neonate can develop complications after birth as breathing causes air to pass from the trachea to the oesophagus and stomach, and feeding results in swallowed milk and stomach acid passing into the lungs. Some babies with TOF also have other congenital anomalies. This is known as VACTERL (vertebral, anal, cardiac, tracheal, (o) esophageal, renal and limb) Figure 3 Midgut herniation. Figure 4 Tracheo-oesophageal fistula. Peristalsis in the intestine occurs from the second trimester. The large bowel is filled with meconium at term. Defecation in utero, and hence meconium in the amniotic fluid, is associated with post-term pregnancies and fetal hypoxia. Aspiration of meconium-stained liquor by the fetus at birth can result in meconium aspiration syndrome and respiratory distress. In the last trimester of pregnancy ,while body water content gradually o diminish, glycogen and fat store increase about five fold. growth restricted and preterm fetus have reduced glycogen storage and therefore more prone to hypoglycemia within early neonatal period. Liver, pancreas and gall bladder The pancreas, liver and epithelial lining of the biliary tree derive from the endoderm of oo the foregut. The liver and biliary tree appear late in the third week or early in the fourth week as the hepatic diverticulum, which is an outgrowth of the ventral wall of the distal foregut. The larger portion of this diverticulum gives rise to the parenchymal cells (hepatocytes) and the hepatic ducts, while the smaller portion gives rise to the gall Oo bladder. By the sixth week, the fetal liver performs hematopoiesis. This peaks at 12– 16 weeks and continues until approximately 36 weeks. In utero, the normal metabolic functions of the liver are performed by the placenta. For example, unconjugated bilirubin from hemoglobin breakdown is actively transported from the fetus to the mother, with only a small proportion being conjugated in the liver and secreted in the bile (the mechanism after birth). The fetal liver also differs from the adult organ in many processes; for example, the fetal liver has a reduced ability to conjugate bilirubin because of relative deficiencies in the necessary enzymes such as glucuronyl transferase. After birth, the loss of the placental route of excretion of unconjugated bilirubin, in the presence of reduced conjugation, particularly in the premature infant, may result in transient unconjugated hyperbilirubinaemia or physiological jaundice of the newborn. Glycogen is stored within the liver in small quantities from the first trimester, but storage is maximal in the third trimester, with abundant stores being present at term. Growth-restricted and premature infants have deficient glycogen 0 stores; this renders them prone to neonatal hypoglycaemia. Kidney and urinary tract The kidney, recognized in its permanent final form (metanephric kidney), is preceded by the development and subsequent regression of two primitive forms; the pronephros and mesonephros. The pronephros originates at about 3 weeks in a ridge that forms on either side of the midline in the embryo, known as the nephrogenic ridge. In this region, epithelial cells arrange themselves in a series of tubules and join laterally with the pronephric duct. Each pronephric duct grows towards the tail of the embryo. It induces intermediate mesoderm in the thoracolumbar area to become epithelial tubules called mesonephric tubules. The pronephros degenerates while the mesonephric (Wolffian) duct extends towards the most caudal end of the embryo, ultimately attaching to the cloaca. During the fifth week of gestation the ureteric bud develops as an out-pouching from the Wolffian duct. This bud grows towards the head of the embryo and into the intermediate mesoderm and as it does so it branches to form the collecting duct system (ureter, pelvic calyces and collecting ducts) of the kidney and induces the formation of the renal secretory system (glomeruli, convoluted tubes, loops of Henle). Subsequently the lower portions of the nephric duct will migrate caudally (downward) and connect with the bladder, thereby forming the ureters. As the fetus develops, the kidneys rotate and migrate upwards within the abdomen, which causes the length of the ureters to increase. Failure of the normal migration of the kidney upwards can result in a pelvic kidney, where it remains in the pelvic area. Abnormal development of the collecting duct system can result in duplications such as duplex kidneys. The most common sites of congenital urinary tract obstructive uropathies are at the pyeloureteric junction, the vesicoureteric junction or as a consequence of posterior urethral valves, an obstructing membrane in the posterior male urethra. Severe obstruction in utero can lead to hydronephrosis and renal interstitial fibrosis. In humans, all of the branches of the ureteric bud and the nephronic units have been formed by 32–36 weeks’ gestation. However, these structures are not yet mature, and the maturation of the excretory and concentrating ability of the fetal kidneys is gradual and continues after birth. In the preterm infant this may lead to abnormal water, glucose, sodium or acid–base homeostasis. As fetal urine forms much of the amniotic fluid, renal agenesis will result in severe reduction (oligohydramnios) or absence of amniotic fluid (anhydramios). Babies born with bilateral renal agenesis (Potter’s syndrome), which is associated with other features such as widely spaced eyes, small jaw and low set ears, results that are secondary to oligohydramnios, do not pass urine and usually die either as a consequence of ‘renal failure’ or pulmonary hypoplasia, again secondary to severe oligohydramnios. Skin and homeostasis 6 20wakabotonaufetnssov.sn Fetal skin protects and facilitates homeostasis. The skin and its appendages (nails, hair) develop from the ectodermal and mesodermal germ layers. The epidermis develops from the surface ectoderm; the dermis and the hypodermis, which attaches the dermis of the skin to underlying tissues, both develop from mesenchymal cells in the mesoderm. By the fourth week following conception, a single-cell layer of ectoderm surrounds the embryo. At about 6 weeks this ectodermal layer differentiates into an outer periderm and an inner basal layer. The periderm sloughs as the vernix, a creamy protective coat that covers the skin of the fetus. The basal layer produces the epidermis and the glands, nails and hair follicles. The epithelium becomes stratified and by 16–20 weeks all layers of the epidermis are developed and each layer assumes a structure characteristic of the adult. Preterm babies have no vernix and thin skin; this allows a large amount of insensible water loss. Hair follicles begin to develop as hair buds between 12 and 16 weeks from the basal layer of the epidermis. By 24 weeks the hair follicles produce delicate fetal hair called lanugo, first on the head and then on other parts of the body. This lanugo is usually shed before birth. Ix  Soniceofislod Blood and immune system yolksakdhiver3CBonetha.ro w Red blood cells and immune effector cells are derived from haematopoietic o cells, first noted in the blood islands of the yolk sac. By 8 weeks the yolk sac is o replaced by the liver as the source of these cells and by 20 weeks almost all of these cells are produced by the bone marrow. The development of the thymus and the secondary lymphoid organs is a highly ordered process that undergoes a rapid expansion in the first trimester of pregnancy and appears to be largely finished by the time of birth. T-cell precursors transit to the thymus by 9 weeks of gestation,circulating c g mature T cells are present by 16 weeks of gestation. Lymphoid precursor cells develop into B-lymphocytes, detected in the fetal liver at 8 weeks of gestation and appear in fetal blood circulation by 12 weeks of gestation. They undergo subsequent functional maturation in secondary lymphoid tissue (e.g. lymph nodes and spleen). although much of the immunoglobulin (Ig) G in the fetus originates from the maternal circulation and crosses the placenta to provide passive immunity to the fetus and neonate. The fetus normally produces only small amounts of IgM and IgA, which do not cross the placenta. Detection of IgM/IgA in the newborn, without IgG, is indicative of fetal infection. or Most haemoglobin in the fetus is fetal haemoglobin (HbF), which has two gamma-chains (alpha-2, gamma-2). This differs from the adult haemoglobins HbA and HbA2, which have two beta-chains (alpha-2, beta-2) and two delta-chains (alpha-2, delta-2), respectively. Ninety percent of fetal haemoglobin is HbF between 10 and 28 0 weeks gestation. From 28 to 34 weeks, a switch to HbA occurs, and at term 5 the ratio of HbF to HbA is 80:20; ….by 6 months of age, only 1% of haemoglobin is HbF. A key feature of HbF is a higher affinity for oxygen than 0 HbA. This is association with higher HB concentration at birth ,nearly 18 g/dl , enhance transfer of oxygen across placenta.Abnormal haemoglobin a production results in thalassaemia. Hba Hbf for or Thalassaemias are a group of genetic hematological disorders characterized by reduced or absent production of one or more of the globin chains of haemoglobin. Beta thalassaemia I results from reduced or absent production of the beta-globin chains. As the switch from HbF to HbA described above occurs, the absent or insufficient beta-globin chains shorten red cell survival, with destruction of these cells within the bone marrow and spleen. Beta-thalassaemia major results from the inheritance of two abnormal beta genes; without treatment, this leads to severe anaemia, FGR, poor musculoskeletal development and skin pigmentation due to increased iron absorption. In the severest form of alpha-thalassaemia, in which no alpha-globin chains are produced, severe fetal anemia occurs with cardiac failure, hepatosplenomegaly and generalized oedema. The infants are stillborn or die Endocrine system Major components of the hypothalamic–pituitary axis are in place by 12 weeks gestation. Thyrotrophin-releasing hormone (TRH) and gonadotrophin-releasing E hormone (GnRH) have been identified in the fetal hypothalamus by the end of the first trimester. Testosterone produced by the interstitial cells of the testis is also synthesized in the first trimester of pregnancy and increases to 17–21 weeks, which mirrors the differentiation of the male urogenital tract. Growth hormone is similarly present from early pregnancy and detectable in the circulation from 12 weeks. The thyroid gland produces T4 from 10 to 12 o weeks. Growth-restricted fetuses exist in a state of relative hypothyroidism, which may be a compensatory measure to decrease metabolic rate and oxygen consumption.  Behavioural states From conception, the fetus follows a developmental path with milestones that continue into childhood. The first activity is the beating of the fetal heart followed by fetal movements at 7–8 weeks. These start as just discernable movements and graduate through startles to movements of arms and legs, breathing movements and by 12 weeks yawning, sucking and swallowing. This means that in the first trimester of pregnancy the fetus exhibits movements that are observed after birth. Four fetal behavioural states have been described, annotated 1F–4F. 1F is quiescence, 2F is characterized by frequent and periodic gross body movements with eye j movements, 3F no gross body movements but eye movements and 4F vigorous continual activity again with eye movements. 1F is similar to quiet or non-REM sleep in the neonate, 2F to REM sleep, 3F to quiet wakefulness and 4F active wakefulness. An understanding of fetal behaviour can assist in assessing fetal condition and wellbeing. Amniotic fluid By 12 weeks’ gestation, the amnion comes into contact with the inner surface of the chorion and the two membranes become adherent, but never intimately fuse. Neither the amnion nor the chorion contains vessels or nerves, but both 00C do contain a significant quantity of phospholipids as well as enzymes involved in phospholipid hydrolysis. Choriodecidual function is thought to play a role in the initiation of labour through the production of prostaglandins E2 and F2a. The amniotic fluid is initially secreted by the amnion, but by the 10th week it is mainly a transudate of the fetal serum via the skin and umbilical cord. From 16 weeks’ gestation, the fetal skin becomes impermeable to water and the net increase in amniotic fluid is through a small imbalance between the contributions of fluid through the kidneys and lung fluids and removal by fetal swallowing. The amniotic fluid contains growth factors as well as multipotent stem cells, the function of which at present is unknown. Amniotic fluid volume o increases progressively (10 weeks: 30 ml; 20 weeks: 300 ml; 30 weeks: 600 ml; 38 weeks: 1,000 ml), but from term there is a rapid fall in volume (40 weeks: 800 ml; 42 weeks: 350 ml). The reason for the late reduction has not been explained. The amniotic fluid index is calculated as the total measurement of the deepest pool in the four quadrants of the uterus. The function of the amniotic fluid is to: e -Protect the fetus from mechanical injury. -Permit movement of the fetus while preventing limb contracture. Prevent adhesions between fetus and amnion. -Permit fetal lung development in which there is two-way movement of fluid into the fetal bronchioles. absence of amniotic fluid in the second trimester is associated with pulmonary hypoplasia. Major alterations in amniotic fluid volume occur when there is reduced contribution of fluid into the amniotic sac in conditions such as renal agenesis, cystic kidneys or FGR; oligohydramnios results. Reduced removal of fluid in conditions such as congenital neuromuscular disorders, anencephaly and oesophageal/duodenal atresia that prevent fetal swallowing is associated with polyhydramnios. KEY LEARNING POINTS Determinants of birthweight are multifactorial, and reflect the influence of the natural growth potential of the fetus and the intrauterine environment. C The fetal circulation is quite different from that of the adult. Its distinctive features are: o – oxygenation occurs in the placenta, not the lungs; – the right and left ventricles work in parallel rather than in series; – the heart, brain and upper body receive blood from the left ventricle, while the placenta and lower body receive blood from both right and left ventricles. Surfactant prevents collapse of small alveoli in the newborn lung during expiration by lowering surface tension. Its production is maximal after 28 weeks. RDS is common in babies born prematurely and is associated with surfactant deficiency.  The fetus requires an effective immune system to resist intrauterine and perinatal infections. Lymphocytes appear from 8 weeks and, by the middle of mm the second trimester, all phagocytic C cells, T and B cells and complement are available to mount a response. Fetal skin protects and facilitates homeostasis. In utero, the normal metabolic functions of the liver are performed by the placenta. The loss of the placental route of excretion of unconjugated bilirubin, in the face of conjugating enzyme deficiencies, particularly in the premature infant, may result in transient unconjugated hyperbilirubinaemia or physiological jaundice of the newborn. Growth-restricted and premature infants have deficient glycogen stores; this renders them prone to neonatal hypoglycaemia. The function of the amniotic fluid is to: – protect the fetus from mechanical injury; – permit movement of the fetus while preventing limb contracture; – prevent adhesions between fetus and amnion; – permit fetal lung development in which there is two-way movement of fluid into the fetal bronchioles; absence of amniotic fluid in the second trimester is associated with pulmonary hypoplasia.