Perinatal disease, prenatal testing and aging

Keep age and size apart. A preterm baby can be the right size for its age (appropriate for gestational age); a term baby can be small (SGA). They have different problems: the preterm baby's organs are immature (surfactant, gut, germinal matrix), while the growth-restricted term baby has mature organs but low reserves (hypoglycemia, hypothermia, polycythemia). Growth restriction that starts early (chromosomal, infection) shrinks head and body together (symmetric); placental insufficiency later in pregnancy spares the head (asymmetric).

Surfactant, mainly dipalmitoylphosphatidylcholine (lecithin) made by type II pneumocytes, lowers alveolar surface tension so that small alveoli stay open at end-expiration. Production starts late in the second trimester and becomes adequate around 34–35 weeks. In a premature lung, alveoli collapse with each breath (atelectasis); the work of breathing soars and blood passes through unventilated lung, causing hypoxemia. Hypoxia injures epithelium and endothelium; plasma proteins leak and fibrin with necrotic cells forms hyaline membranes in the alveolar ducts.

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Necrotizing enterocolitis is the most common gastrointestinal emergency of premature infants. An immature mucosal barrier, reduced blood flow (ischemia) and bacterial colonization, typically after formula feeding has started, combine to injure the bowel wall, usually the terminal ileum and right colon. Infants develop feeding intolerance, abdominal distension and bloody stools; the radiograph shows gas in the bowel wall (pneumatosis intestinalis), sometimes portal venous gas or free air after perforation. Survivors may develop strictures or short-bowel syndrome. Breast milk and antenatal steroids lower the risk.

Intraventricular hemorrhage starts in the germinal matrix, a richly vascular zone beside the lateral ventricles that involutes by about 34 weeks. Its thin-walled vessels rupture when cerebral blood flow fluctuates (hypoxia, hypercapnia, blood-pressure swings) in an infant who cannot autoregulate, usually within the first 3 days in babies born before 32 weeks. Blood can extend into the ventricles and the adjacent white matter; posthemorrhagic hydrocephalus and cerebral palsy can follow. Screening cranial ultrasound finds it.

Sudden infant death syndrome is the sudden death of an infant under 1 year that remains unexplained after a complete autopsy, death-scene investigation and review of the history; it peaks at 2–4 months, usually during sleep. A triple-risk model explains it: a vulnerable infant (often subtle brainstem serotonergic abnormalities that blunt arousal and autoresuscitation), a critical developmental period, and an external stressor (prone sleeping, soft bedding, overheating, bed-sharing, tobacco smoke). Prenatal and postnatal smoking, prematurity and low birth weight add risk. Supine sleep on a firm surface, room-sharing without bed-sharing, breastfeeding and a smoke-free home lower it.

Screening tests are offered to every pregnant woman, carry no risk to the fetus and give a probability. Diagnostic tests sample fetal (or placental) cells and give an answer, at a small procedural risk. A positive screen is never a diagnosis; a negative screen does not exclude disease.

α-Fetoprotein is made by the yolk sac and fetal liver, enters fetal serum, is excreted in fetal urine into the amniotic fluid and crosses into maternal blood. When the neural tube is open, fetal serum leaks directly into the amniotic fluid, so AFP rises in amniotic fluid and maternal serum (acetylcholinesterase in amniotic fluid confirms an open defect). It also rises with abdominal wall defects, multiple pregnancy, fetal death and underestimated gestational age, and is low in Down syndrome.

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Aging is the gradual decline in a cell's ability to divide, repair and keep its proteins and membranes intact. The lecture lists several theories; they are best read as overlapping mechanisms, each with a disease that exaggerates it.

Hutchinson–Gilford progeria shows how one base can age a child. A de novo, autosomal dominant point mutation in LMNA (c.1824C>T) does not change its own amino acid, but it activates a cryptic splice site that deletes 50 amino acids, including the cleavage site that normally removes lamin A's farnesyl anchor. The truncated, permanently farnesylated protein, progerin, stays stuck in the inner nuclear membrane, deforms the nucleus (blebbing), and disturbs chromatin, DNA repair and telomeres. Growth falters from 6–18 months; children lose hair and subcutaneous fat, develop scleroderma-like skin, a beaked nose, micrognathia and osteopenia, keep normal intelligence, and die of atherosclerosis (myocardial infarction, stroke) in their teens. A farnesyltransferase inhibitor (lonafarnib) prolongs survival.