1. Pediatric Fundamentals Prenatal Growth and Development Drs. Greg and Joy Loy Gordon January 2005

2. Pediatric Fundamentals – Prenatal Growth and Development Prenatal Embryonic period first 8 weeks Organogenesis 4 th – 8 th weeks Ectoderm Mesoderm Endoderm

3. Pediatric Fundamentals – Prenatal Growth and Development Organogenesis 4th – 8th weeks Ectoderm nervous system skin sweat and mammary glands teeth epithelial structures of eyes, ears, neck

4. Pediatric Fundamentals – Prenatal Growth and Development Organogenesis 4th – 8th weeks Mesoderm somites dermis and epidermis cardiovascular system urogenital system spleen adrenal cortex

5. Pediatric Fundamentals – Prenatal Growth and Development Organogenesis 4th – 8th weeks Mesoderm somites myotomes -> segmental muscles of trunk dermatomes -> dermis of scalp, neck, trunk sclerotomes -> vertebral bodies, arches abnormal induction -> spinal bifida

6. Pediatric Fundamentals – Prenatal Growth and Development Organogenesis 4th – 8th weeks Endoderm epithelia digestive respiratory bladder parenchyma liver pancreas thyroid gland parathyroid glands thymus salivary glands

7. Pediatric Fundamentals – Prenatal Growth and Development Developmental Abnormalities congenital diaphragmatic hernia (CDH) esophageal atresia spina bifida Hirschsprung’s disease omphalocele gastroschisis

8. Pediatric Fundamentals – Prenatal Developmental Abnormalities Congenital diaphragmatic hernia (CDH) 1 in 2,500 live births 85% left side of diaphragm defect in closure of pleuroperitoneal canal impaired lung growth prenatal (intrauterine) repair possible

9. Pediatric Fundamentals – Prenatal Developmental Abnormalities Esophageal atresia failure of proliferation of esophageal endoderm in 5 th week 5 types – some with associated tracheoesophageal fistula + E = H-type (7%) 80% 10% 1% 2%

10. Pediatric Fundamentals – Prenatal Developmental Abnormalities Spina bifida failure of closure of posterior neural tube during 3 rd embryonic week mild: spina bifida occulta severe: meningomyelocele 80% lumbosacral in utero repair described

11. Pediatric Fundamentals – Prenatal Developmental Abnormalities Hirschsprung’s disease defect in neural crest migration leads to paralysis of that segment of colon with subsequent proximal dilation

12. Pediatric Fundamentals – Prenatal Developmental Abnormalities 1 in 2,500 live births failure of return of midgut from yolk sac to abdomen by 10 weeks often associated with other abnormalities Omphalocele

13. Pediatric Fundamentals – Prenatal Developmental Abnormalities 1 in 10,000 live births abdominal wall defect between developing rectus muscles just lateral to umbilicus right side may be due to abnormal involution of right umbilical vein during 5 th and 6 th weeks usually not associated with other defects Gastroschisis

14. Pediatric Fundamentals – Prenatal Growth and Development Consequences of maternal disorders on intrauterine development epilepsy history of previous child with neural tube defect diabetes mellitus substance abuse alcohol tobacco cocaine benzodiazepines infectious diseases rubella toxoplasmosis human immunodeficiency virus (HIV) herpes simplex

15. Pediatric Fundamentals –Consequences of Maternal Disorders Epilepsy Congenital anomalies 2 to 3 times more frequent Appear to associated with increase risk of malformation: phenytoin valproic acid multidrug therapy Neural tube defects (e.g. spina bifida) valproic acid carbamazepine low dose folate may decrease risk

16. Pediatric Fundamentals – Consequences of Maternal Disorders History of previous neural tube defect: Risk of subsequent neural tube defect increased 10 times

17. Pediatric Fundamentals – Consequences of Maternal Disorders Diabetes mellitus Increased incidence of stillbirth congenital malformations risk of major malformation (8 times greater) increased rate of high birth weight hypertophic cardiomyopathy in IDM

18. Pediatric Fundamentals – Consequences of Maternal Disorders Substance abuse alcohol Fetal alcohol syndrome intrauterine growth retardation (IUGR) microcephaly characteristic facies CNS abnormalities with intellectual deficiency Increased incidence of other major malformations

19. Pediatric Fundamentals – Consequences of Maternal Disorders Tobacco Low birth weight Cocaine prematurity clinical seizures EEG abnormalities neurobehavioral abnormalities cerebral hermorrhagic infarction Benzodiazepines: no clear teratogenic link sedation and/or withdrawal symptoms reported

20. Pediatric Fundamentals – Consequences of Maternal Disorders Infectious disease Rubella Chromosomal abnormalities IUGR Ocular lesions Deafness Congenital cardiomyopathy Especially with infections before week 11

21. Pediatric Fundamentals – Consequences of Maternal Disorders Infectious disease Toxoplasmosis IUGR Nonimmune hydrops Hydrocephalus Microcephally Later neurologic damage Prompt spiramycin Rx until after delivery decreases risk 50%

22. Pediatric Fundamentals – Consequences of Maternal Disorders Infectious disease Human immunodeficiency virus (HIV) Transmission to fetus: 12 – 30% less if mother taking Zidovudine (no teratogenesis reported) First signs appear at 6 months of age Median survival 38 months

23. Pediatric Fundamentals – Consequences of Maternal Disorders Infectious disease Herpes simplex Neonatal infections Two-thirds caused by asymptomatic genital infection High morbidity and mortality Seizures Psychomotor retardation Spasticity Blindness Learning disabilities Death Maternal active infection: C-section indicated to decrease risk

24. Pediatric Fundamentals – Consequences of Maternal Disorders IUGR 3-7% of all pregnancies Major cause of perinatal morbidity and mortallity Prognosis depends on specific cause Up to 8% have major malformations Head growth important determinant of neurodevelopmental outcome (IUGR + HC abnormal neurodevelopment likely) Hemodynamic changes and/or infectious disease often involved

25. Pediatric Fundamentals – Prenatal Growth and Development Knowledge of normal and abnormal development needed for best intraop care of neonate with congenital malformation or complication of premaurity Diagnosis and prenatal transfer of fetus with major malformation now possible Improvements in neonatal care → lowering of gestational age compatible with long-term survival more premature infants presenting for anesthesia for surgery