Diagnose, counsel and plan management for major fetal structural anomalies

In one line

A major fetal structural anomaly is a diagnosis made on ultrasound that demands three separate consultant judgements — what it is, what it means for this baby, and what this woman wants done about it — and the single principle that organises all of them is that accurate characterisation (lethal vs survivable, isolated vs syndromic, operable vs not) must precede any counselling, because the prognosis you give determines the choice she is allowed to make.

Mechanism & pathophysiology

Structural anomalies arise when a developmental programme is interrupted, and the timing of the insult predicts the lesion more reliably than its cause. Most major malformations are written before the woman knows the gestation she will eventually be scanned at — which is why the 18–22-week scan is a record of embryology already completed, not a window onto a process you can still influence.

Neural-tube defects are the cleanest example. The neural plate folds and the neural tube closes between days 22 and 28 post-conception — before six menstrual weeks. Failure of cranial closure gives anencephaly (no calvarium, no functioning forebrain — uniformly lethal); failure of caudal closure gives open spina bifida (myelomeningocele), in which exposed neural tissue is damaged both by the primary defect and by a "second hit" of chronic chemical and mechanical injury from amniotic fluid across the rest of pregnancy. That second-hit model is the entire rationale for in-utero repair: close the defect before the cord finishes being destroyed. Open NTDs also drive cerebrospinal-fluid leak that collapses the posterior fossa and pulls the hindbrain down through the foramen magnum — the Chiari II malformation — which is what produces the ventriculomegaly and the "lemon" and "banana" cranial signs that flag the spine long before you see the spine itself. Folate's role is upstream of all of this: it supports the one-carbon methylation that the closing neuroepithelium depends on, which is why periconceptional folate, started before closure, prevents the defect and folate started at booking does nothing.

Congenital heart disease is the commonest serious anomaly group (roughly 6–8 per 1000 births) and the most frequently missed, because the four-chamber view that screening relies on is normal in the very lesions that kill early — transposition, coarctation, interrupted arch — where the abnormality is in the outflow tracts and great-vessel connections. The cardiac neural crest and the looping and septation of the primitive heart tube happen across weeks 4–8; a disturbance there (often with a genetic substrate — 22q11.2 deletion behind conotruncal lesions, trisomies behind atrioventricular septal defects) yields a structurally fixed heart by the time it can be imaged. The functional grouping that matters for delivery planning is whether the circulation is duct-dependent: lesions like transposition, critical coarctation, hypoplastic left heart and pulmonary atresia keep the neonate alive only while the arterial duct stays open, so they must be delivered where prostaglandin can be started and a paediatric cardiac service reached — the antenatal diagnosis is what buys that preparation, which is the whole point of looking for CHD before birth. Transposition is the exception in this group: survival depends on mixing, principally at the atrial level (the foramen ovale) as well as through the duct, so a restrictive foramen ovale may need an emergency balloon atrial septostomy and prostaglandin alone can be insufficient.

Twin–twin transfusion syndrome is the one "structural" lesion of the placenta rather than the fetus, and it belongs here because it is the commonest fetal-therapy referral and the lesion behind one of the field's defining trials. In a monochorionic twin pregnancy, unbalanced flow across shared placental vascular anastomoses creates a hypovolaemic, oliguric, oligohydramniotic donor and a hypervolaemic, polyuric, polyhydramniotic recipient at risk of cardiac failure and hydrops. Untreated severe TTTS before viability is largely lethal for both twins; the rationale for fetoscopic laser is to coagulate the communicating vessels and convert one shared circulation into two separate ones, which is why laser treats the cause and amnioreduction only the symptom.

Congenital diaphragmatic hernia is a failure of the pleuroperitoneal membrane to close by week 10, letting abdominal viscera herniate into the chest. The hernia itself is rarely the problem; the lethal lesion is the pulmonary hypoplasia and pulmonary vascular maldevelopment caused by lung compression during the canalicular and saccular phases. Prognosis therefore tracks lung volume, not hernia size — which is the conceptual key to fetal therapy for CDH.

Abdominal-wall defects separate on embryology into two diseases that look superficially similar and behave oppositely. Gastroschisis is a paraumbilical (almost always right-sided) defect with no covering membrane — free loops of bowel exposed to amniotic fluid; it is a vascular/disruptive event, usually isolated, with a low aneuploidy rate but a real risk of bowel injury, and its epidemiology is strikingly young-maternal-age and rising. Exomphalos (omphalocele) is a midline defect with the herniated viscera covered by a peritoneal-amniotic membrane and the cord inserting on the sac — a failure of physiological midgut return, with a high rate of associated chromosomal and syndromic disease (trisomies 13/18, Beckwith–Wiedemann). The membrane is the discriminator that should reorganise the whole workup: its presence raises the karyotype and cardiac stakes.

Renal-tract anomalies span a spectrum from lethal to incidental. Bilateral renal agenesis or bilateral multicystic dysplasia produces anhydramnios from mid-pregnancy and, through it, the pulmonary hypoplasia and limb contractures of the Potter sequence — lethal with standard care. An experimental therapy, serial amnioinfusion before viability followed by neonatal dialysis and eventual transplant, was tested in the RAFT trial (JAMA 2023): 82% of live-born infants reached 14 days with dialysis access but only about 35% survived to discharge on dialysis, with profound prematurity and morbidity, and it is confined to research programmes with little or no routine South African access. Lower-urinary-tract obstruction (commonly posterior urethral valves in a male fetus) gives a distended bladder, hydronephrosis and oligohydramnios, and is the lesion fetal shunting was designed for. The amniotic-fluid volume, again, is the prognostic variable, because mid-trimester fluid is fetal urine and fluid drives lung growth.

Skeletal dysplasias are disorders of bone formation and growth, ranging from the lethal (thanatophoric dysplasia, osteogenesis imperfecta type II, achondrogenesis — recognised by severe early limb shortening, a small chest predicting pulmonary hypoplasia, and fractures or absent ossification) to the survivable. The lethal-versus-not distinction once more comes down to thoracic dimensions and lung volume.

A single thread runs through every group above: the lesion you can image is fixed, but the outcome is usually set by a second-order consequence — fluid volume, lung volume, neural injury over time — and it is those second-order variables, not the named malformation, that a consultant counsels and plans around.

Assessment

The diagnostic spine of this objective is the systematic mid-trimester anomaly scan, the targeted scan that follows an abnormal finding, and the adjuncts (echocardiography, MRI, invasive testing) that resolve what ultrasound leaves uncertain.

• The 18–22-week scan is the screening backbone. The ISUOG minimum survey is a defined checklist — head shape and internal structures, spine in three planes, the abdominal wall and cord insertion, stomach, kidneys and bladder, a four-chamber view and the outflow tracts, the limbs, and biometry — performed to a standard that earlier (e.g. 11–14-week) scanning cannot replace. Its detection rate is genuinely operator-, machine- and habitus-dependent: high (often >90%) for anencephaly and major wall defects in good hands, but mediocre for cardiac and renal lesions even in audited services. State that limitation honestly — a "normal anomaly scan" reduces but does not abolish the chance of a major anomaly, and never excludes a normal-variant lesion that declares later.
• Soft markers (echogenic intracardiac focus, echogenic bowel, mild pyelectasis, short femur/humerus, single umbilical artery, choroid-plexus cysts, an absent or hypoplastic nasal bone, increased nuchal fold) are weak signals for aneuploidy whose entire interpretation has been rewritten by cfDNA. In a woman who has had a low-risk cfDNA result, an isolated soft marker has almost no residual predictive value and should not, on its own, trigger amniocentesis — chasing isolated soft markers in the cfDNA era generates anxiety and invasive procedures without yield. The exceptions are markers that are themselves structural problems demanding their own workup regardless of karyotype — echogenic bowel (which also flags cystic fibrosis, congenital infection and swallowed blood), and any marker found in a cluster or alongside a true structural anomaly, where the genetic threshold drops sharply.
• A targeted / detailed scan by a fetal-medicine operator is the next step for any abnormal finding: it characterises the lesion fully, deliberately searches for associated anomalies (the single most important determinant of prognosis is whether the lesion is isolated or part of a syndrome), and re-reads the markers in that context.
• Fetal echocardiography is the dedicated cardiac study, indicated for a suspected cardiac abnormality, an extracardiac anomaly, an abnormal cardiac axis or four-chamber view, certain aneuploidies, maternal diabetes or anti-Ro/La, a family history, and increased nuchal translucency. It exists because the screening four-chamber view misses outflow-tract disease.
• Fetal MRI is an adjunct, not a screening tool, and earns its place mainly in the central nervous system, where ultrasound is limited by ossification and fetal position. In ultrasound-diagnosed ventriculomegaly, MRI improved diagnostic accuracy to 98.7% versus 89.9% for ultrasound and changed the prognostic category in nearly a quarter of cases — which is why a fetus with isolated ventriculomegaly should be offered MRI before counselling is finalised. It also clarifies posterior-fossa, midline and cortical-malformation questions and helps with CDH (lung volume), thoracic and complex body-wall lesions.
• Invasive testing confirms the genetics. CVS (from ~11 weeks, placental tissue) and amniocentesis (from ~15 weeks, amniocytes) are the access routes; the test on the sample matters more than the route. Chromosomal microarray has displaced standard karyotype as the first-line investigation for a structural anomaly because it detects clinically significant copy-number variants that a karyotype cannot see, with an incremental yield of roughly 6% over karyotype in structurally abnormal fetuses; targeted gene panels and exome sequencing extend this where a microarray is normal but a syndromic picture persists. Which sample route is chosen turns on gestation and what is visible — CVS earlier and where a quick result changes the termination decision, amniocentesis later and where amniotic-fluid studies (infection, fluid for additional tests) are also wanted — and every invasive procedure in a rhesus-negative, non-sensitised woman is an indication for anti-D prophylaxis because of the fetomaternal haemorrhage it can cause. The technique, contraindications and procedure-specific complications of CVS and amniocentesis are a topic in their own right.