GP PREFI EVALS PART 2

• high incidence of spontaneous abortions, premature labor, placental abnormalities
• low birth weight
• prone to SIDS

o mutagenic, carcinogenic, teratogenic o cause malformations such as microcephaly, blindness, skull defects, spina bifida

result of inheritance of multiple genetic polymorphisms that confer a “susceptibility phenotype” -interaction with environment is required before the disorder becomes manifested

decreased incidence of neural tube defects is by intake of

Congenital dislocation of the hip genetic factor

Congenital dislocation of the hip environmental factor

In this period, an injurious agent damages either enough cells to cause death and abortion or only a few cells, presumably allowing the embryo to recover without developing defects

the embryo is extremely susceptible to teratogenesis;

During this period, organs are being crafted out of the germ cell layers

The fetus is susceptible to growth restriction or injury to already formed organs. Thus a given agent may produce different anomalies if exposure occurs at different times of gestation.

Mode of action of cyclopamine

mutations in hedgehog signaling cause

o an antiepileptic o recognized teratogen during pregnancy

Mode of action of valporic acid

mutations in HOX cause same features in

o vitamin A (Retinol) derivative o absent during embryogenesis

• malformations affecting multiple organ systems
• essential for normal development and differentiation

Mode of action of All-trans-retinoic acid

mutations in Tgfb3 gene cause

➔ gestational age less than 37 weeks ➔ 2nd most common cause of neonatal mortality

Appropriate for gestational age (AGA)

Small for gestational age (SGA)

Large for gestational age (LGA)

Preterm

Post-term

refers to spontaneous ROM occurring BEFORE 37 weeks of gestation

refers to spontaneous ROM occurring AFTER 37 weeks of gestation

the major cause of preterm labor with and without intact membranes o present in ~25% of all preterm births

inflammation of the placental membranes

inflammation of the fetal umbilical cord

Most common microoganisms in intrauterine infection

Uterine, cervical, and placental structural abnormalities

hyaline membrane disease

• Refer to some infants (1/3) who weigh less than 2500 gm despite being born at term
• undergrown rather than immature
• suffer from fetal growth restriction (aka intrauterine growth retardation)

• intrinsically reduce growth potential despite an adequate supply of nutrients
• characterized by symmetric growth restriction (proportionate FGR)

Diseases under fetal abnormalities

Most common microorganisms that cause fetal infections

most common factor associated with SGA infants: maternal conditions that result in decreased blood flow

toxemia of pregnancy

Maternal abnormalities

• uteroplacental insufficiency
• result in asymmetric or disproportionate growth retardation with relative sparing of the brain
• viewed as downregulation of growth in late half of gestation d/t limited availability of nutrients and oxygen

umbilical-placental vascular anomalies

results from viable genetic mutations occurring AFTER zygote formation

Most frequently documented chromosomal mosaicism

occur at the time of the 1st and 2nd postzygotic division

• occurs later and within dividing trophoblast or extraembryonic progenitor cells of the inner cell mass
• limited to placenta

Strong associations of RDS

Within 30 minutes of RDS

Within a few hours of RDS

Within few hours of RDS, A chest radiograph at this time usually reveals uniform minute reticulogranular densities, producing a so-called

The fundamental defect in RDS is

hydrophobic surfactant proteins

Surfactant proteins that play a role in pulmonary host defense (innate immunity)

Surfactant proteins that are involved in reduction of surface tension at the air-liquid barrier

Mutations in SFTPB and SFTBC results in

Cells that produce surfactant

Glucocorticoids play an important role because increased corticosteroid release (d/t intrauterine stress and FGR) will lead to

Major thrust in the control of RDS focuses on prevention via

• expression of VEGF is markedly decreased
• cause endothelial cell apoptosis

cause lesions in the retina

reversible impairment in development of septation at saccular stage

Cytokines released during Bronchopulmonary dysplasia

the presence of gas within the wall of the small or large intestine

Perinatal infections primary routes of infection

Most bacterial and few viral infections (e.g., herpes simplex II) are acquired by what route

• Causes erythema infectiousum or 5th disease of childhood
• Has a particular tropism for erythroid cells

Occurs within the first 7 days of life, Most common cause: Group B Streptococcus

From 7 days to 3 months of life, Infections with Listeria and Candida

Accumulation of edema fluid in the fetus during intrauterine growth

A hemolytic disease caused by blood group antigen incompatibility between mother and fetus

What are the major antigens in immune hydrops?

Only major cause of Rh incompatibility

Hemolytic disease occurs almost exclusively in infants of

o Direct result of red cell loss o May result in hypoxic injury to the heart and liver

bilirubin blinds to lipids in the brain and can damage the CNS, causing

Chromosomal anomalies associated with fetal hydrops

abnormalities of lymphatic drainage from the neck → lead to postnuchal fluid accumulation or cystic hygromas

• deletion of all four a-globin genes
• most common cause of nonimmune hydrops

bilirubin level that can cause neural damage

Caused by biallelic mutations of the gene encoding phenylalanine hydroxylase (PAH)

Normal [Phe]

Classic [Phe] in PKU

Defects in BH4 recycling disturb the synthesis of

Abnormalities in synthesis and recycling of this cofactor will also lead to PKU