Effects of maternal disease on foetus Flashcards
Describe the feto-maternal interface
- Umbilical cord
- Umbilical vein
- Umbilical arteries (x2)
-
Chorionic villi: sprout from chorion to increase contact with
maternal blood - invade and destroy uterine decidua and
absorb nutrients to support embryo. Umbilical artery and vein go through chorionic villi, uterine artery and vein come into placenta and towards chorionic villi. Circulations are shared through intervillous space. - Layers:
- Amnion: membrane that closely covers embryo - fills with amniotic fluid which protects embryo
- Chorion: outermost foetal membrane that develops
from outer fold of yolk sac
- Placenta grows through myometrium to create transfer of maternal blood in and foetal blood out
Summarise the mechanisms of effect of maternal disease
- Transplacental disease
- Infections, antibodies
- Altered fetal physiology
- Diabetes (glucose BUT NOT INSULIN crosses placenta)
- Nutritional status of the mother
- Obesity, malnutrition
- Interference with fetal respiration or nutrition
- Cardiac disease, anemia, hypertension
- Miscarriage/preterm or induced labor
- Ascending infection
Describe the determinants of a solute crossing the placenta
- Depends on size, shape, and charge of the molecule
- Passive and facilitated diffusion, or active transport
- Too Big: bacteria, heparin, IgM (900,000)
- IgG can cross (150,000) to provide some passive immunity
Describe how timing affects impact of insult on foetus
Depending on when the insult impacts the foetus there will be different effects as there are different periods of foetal growth.
- Fetal growth:
- Sequential cellular hyperplasia: 4-20 weeks
- Hyperplasia plus hypertrophy: 20-28 weeks
- Hypertrophy alone: 28-40 weeks
- Organogenesis 3 to 8 weeks after LMP
- Teratogenesis: e.g., rubella, diabetes, drugs, therefore, importance of health preconception: nutrition, metabolic diseases, smoking, alcohol, folic acid
- Risk of unwell mother to foetus are higher than some medications to treat conditions
Describe teratogens and their effect (teratogenesis)
- Teratogens may be infectious agents, drugs, physical agents, glucose
- Interfere with
- Cellular growth
- Differentiation
- Interaction
- Migration
- ALL critical processes in embryogenesis
Describe IUGR
- Characterised by decreased cell size
- If early enough also decreased cell number
- Vascular disease, infection, chromosomal disorder
- Symmetrical vs asymmetrical IUGR
- symmetrical is phenotypic - entire body is proportionally small
- pathologic growth restriction is asymmetrical: protects things that are most essential e.g. brain and kidneys - head is normal, limbs are thin and small
- Selective sparing of cerebral circulation
Provideexamples of perinatal infections
- Toxoplasmosis, rubella, CMV, syphilis cause fetal syndromes: all pregnant women in Australia are screened for syphilis
- Parvovirus B19 – fetal anemia & hydrops (fluid in limbs, organs causing swelling)
- Listeriosis – miscarriage
- HIV – vertical transmission
- Congenital rubella
Describe diabetes in pregnancy
Can be pre-existing diabetes (IDDM or NIDDM), or gestational diabetes (due to pre-existing diabetes, or GDM - managed with education, advice and sugar monitoring)
- Placental hormones diabetogenic: progesterone, hPL, cortisol. Increases maternal risk of DM
- increased glucose crosses gradient with facilitated transport; as a result, Fetal glucose ends up 2/3 of maternal. But insulin can’t cross, thus mother’s insulin cannot help baby dela with glucose, and baby is unable to secrete enough insulin to deal with increased glucose
- First trimester – increased glucose is teratogenic
- Miscarriage, sacral agenesis, spina bifida, cardiac defects
- Directly related to periconceptual glycaemia – when sugars normal, defects do not occur
- Later: insulin acts as a growth factor: macrosomia
- Increased risk of shoulder dystocia (an obstetric emergency in which the anterior shoulder of the infant cannot pass below the pubic symphysis after delivery of the head) ^[need C-section], stillbirth, especially if pre-existing vascular disease: iugr
- Insulin inhibits surfactant, increased incidence of hyaline membrane disease –alveoli collapse, impairing gas exchange after birth
- Cardiac defects, sacral agenesis
Describe the challengesand briefly describe effect of obesity
- 50% of pregnant women BMI > 25
- One of the major challenges in obstetric care
- Stillbirth & miscarriage
- Abnormal fetal growth & development
- Increased NTDs
- Body habitus makes assessment difficult
- Increased risk of pre-eclampsia, diabetes, thromboembolism
- Also increases risk of metabolic dysfunction in child
Describe the link between obesity and malnutrition
- Foetal programming by nutritional stimuli and adaptation to supply of nutrients
- Barker Hypothesis
- “Thrifty phenotype”: epidemiological association between poor foetal health and infant growth
- “Developmental plasticity”: ability of a genotype to produce multiple forms and behaviors in response to environmental conditioning
- Fetus trades off development of non-essential organs e.g., kidney & pancreas - High birth weight also linked to permanent long-term metabolic and physiological change
- Obesity a self-perpetuating problem in succeeding generations
Describe the effects of maternal antibodies
- IgG confers passive immunity to the fetus BUT may also be harmful
- SLE
- autoantibodies
- ANA
- Anti ds-DNA
- Anti-Ro and Anti-La (Associated with foetal arrhythmias)
- ACA
- LAC
- association with IUGR, and IUFD: mechanism unclear, may be related to transplacental antibodies
- autoantibodies
- Rhesus & platelet incompatibility
- Antithyroid antibodies in Graves disease
NOTE: IgM cannot cross the placenta
Briefly describe maternal vascular diseases
- Pre-eclampsia/gestational -> pregnancy induced hypertension after 20 weeks gestation, with either proteinuria or end-organ dysfunction
- Thrombophilias -> lead to placental dysfunction and intrauterine restriction or death
- Connective tissue disorders
Describe hypertension in pregnancy and discuss pre-eclampsia
- Increased BP in pregnancy
- Pre-existing HT
- Gestational hypertension
- Super-imposed PE
- Pre-eclampsia (PE)
- BP > 140/90
- Proteinuria
- Edema
- Pathology of Pre-eclampsia
- PE is a placental disease characterized by specific placental histopathological changes (atherosis, infarction)
- Placental ischemia
- Fetal growth restriction
- Maternal hypertension
- Multiple organ systems failure
- Renal, hepatic, clotting
- PE is a placental disease characterized by specific placental histopathological changes (atherosis, infarction)
Describe maternal anaemias
- Iron deficiency
- Physiological anemia in pregnancy, normal as TBW increases (dilutional anaemia)
- Thalassemias
- Autosomal recessive disorders of globin synthesis
- Varying levels of severity
- Sickle cell disease
- Pregnancy worsens maternal disease
All can lead to : Miscarriage, preterm delivery, IUGR
- Pregnancy worsens maternal disease
- Cardiac Disease
- Malnutrition
- Vitamin D deficiency
Describe the effect of drugs in pregnancy
Altered maternal physiology
- Increased blood volume and cardiac output
- Increased renal clearance: first pass effect - PK of drugs change, therefore doses may need o change
- Induction of hepatic enzymes by estrogen
- Slowed gastric emptying
- Categories of prescribing
- Based on evidence of harm
- A, B1, B2, B3, C, D & X
- Need may outweigh risk
- Epilepsy
- Depression
- Hypertension
- Chemotherapy e.g., breast cancer
e.g. of consequences: spina bifida, cleft lip and palate
Describe the effect of alcohol in pregnancy
- Fetal alcohol syndrome is characterised by
- LBW
- Distinct cranio-facial features
- Decreased IQ
- Renal & cardiac effects
- Even moderate exposure has led to FAS
- Therefore, NO safe level of alcohol consumption nor safe time
