For a 32-week fetus with unexpectedly severe asymmetric FGR and bilateral uterine/UA abnormalities
Several maternal systemic diseases can mimic or present with a preeclampsia-like picture, particularly new hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, renal dysfunction, or hemolysis.
Important differentials for “preeclampsia-like” presentation
| Condition | Features that can mimic preeclampsia | Clues favoring the condition |
|---|---|---|
| SLE / lupus nephritis | HTN, proteinuria, renal dysfunction, thrombocytopenia | Low C3/C4, anti-dsDNA ↑, active urine sediment, pre-existing autoimmune disease |
| Antiphospholipid syndrome (APS) | HTN, proteinuria, thrombocytopenia, placental insufficiency | Thrombosis/recurrent pregnancy loss, lupus anticoagulant/ anticardiolipin/β2-GPI antibodies |
| Thrombotic thrombocytopenic purpura (TTP) | HTN, thrombocytopenia, renal dysfunction, neurological symptoms | Marked thrombocytopenia + microangiopathic hemolysis , ADAMTS13 severely reduced |
| Atypical HUS / complement-mediated TMA | HTN, AKI, thrombocytopenia, hemolysis | Prominent renal failure, persistent TMA postpartum; complement abnormalities |
| HELLP syndrome | Can overlap almost completely with severe preeclampsia | Hemolysis + elevated AST/ALT + low platelets |
| Acute fatty liver of pregnancy (AFLP) | Hypertension/proteinuria may occur | Hypoglycemia, jaundice, coagulopathy, elevated bilirubin, leukocytosis |
| Chronic kidney disease / glomerulonephritis | HTN + proteinuria | Proteinuria/renal dysfunction before 20 weeks or pre-existing CKD |
| Diabetic nephropathy | HTN + proteinuria | Long-standing diabetes, retinopathy, pre-existing albuminuria |
| Pheochromocytoma | Severe/paroxysmal hypertension | Headache, palpitations, sweating; very high metanephrines |
| Thyrotoxicosis | HTN, tachycardia, abnormal LFTs | Suppressed TSH, elevated FT4/FT3 |
| Systemic infection/sepsis | Thrombocytopenia, renal/liver dysfunction | Fever, inflammatory markers, positive cultures/source |
| APS-related TMA | HTN, renal dysfunction, thrombocytopenia | Antiphospholipid antibodies + thrombosis/placental disease |
IBD
Pregnancy with Crohn disease or ulcerative colitis, particularly with active disease, is associated with increased risk of:
• Gestational hypertension and preeclampsia
• Fetal growth restriction
• Preterm birth
• Placental dysfunction
An important clinical point is that active IBD can cause hypoalbuminemia, anemia, inflammation, and nutritional deficiencies, which can complicate interpretation of maternal and fetal findings.
Celiac disease
Untreated or active celiac disease is also associated with increased risk of:
• Preeclampsia/hypertensive disorders
• Fetal growth restriction
• Low birth weight
• Preterm birth
• Placental complications
This is thought to relate to malabsorption, micronutrient deficiency, chronic inflammation, and abnormal placentation.
bilateral raised uterine artery resistance + severe FGR can be the first visible manifestation of maternal systemic vascular, renal, autoimmune, metabolic, or inflammatory disease Maternal conditions
| Undiagnosed Maternal Disease | Why It Can Produce This Phenotype | What May Give It Away |
|---|---|---|
| Chronic hypertension / masked hypertension | Abnormal spiral-artery remodeling and maternal vascular malperfusion | Home BP, nocturnal BP, previous borderline BP |
| Chronic kidney disease | Endothelial dysfunction + impaired placentation | Creatinine, urine ACR/PCR, microscopic hematuria |
| IgA nephropathy / occult glomerulopathy | Can be clinically silent until pregnancy | Proteinuria, hematuria, mildly abnormal creatinine |
| Lupus nephritis / SLE | Immune-mediated endothelial/placental injury | Proteinuria, thrombocytopenia, low C3/C4, ANA/anti-dsDNA |
| Antiphospholipid syndrome | Placental thrombosis and maternal vascular malperfusion | Previous losses, thrombosis, autoimmune history, APS antibodies |
| Complement-mediated TMA / aHUS predisposition | Endothelial injury and placental microangiopathy | Thrombocytopenia, hemolysis, renal dysfunction, postpartum persistence |
| Undiagnosed metabolic syndrome / diabetes | Vascular dysfunction and abnormal placentation | HbA1c, fasting glucose, dyslipidemia |
| Thyroid disease, particularly autoimmune thyroid disease | Associated with hypertensive disease and placental dysfunction | TSH, FT4, TPO Ab |
| Celiac disease | Malabsorption/inflammation and adverse placental outcomes | Iron/B12/folate deficiency, low albumin, GI symptoms may be subtle |
| IBD | Systemic inflammation, nutritional compromise, vascular/placental effects | CRP, anemia, low albumin, occult bowel symptoms |
| Inflammatory/autoimmune disease without classic symptoms | Chronic endothelial activation | ESR/CRP, ANA profile, clinical review |
| Severe maternal anemia / nutritional deficiency | Reduced oxygen delivery and impaired fetal growth | Hb, ferritin, B12, folate |
| Sleep-disordered breathing / obesity-related vascular disease | Intermittent hypoxia and endothelial dysfunction | Snoring, witnessed apneas, resistant hypertension |
| Thrombophilic states | Possible placental thrombotic lesions, although routine inherited thrombophilia testing is not generally useful for isolated FGR | Personal/family VTE history |
1. Occult renal disease
Probably underappreciated. A woman can have relatively normal serum creatinine because pregnancy lowers creatinine, while having significant proteinuria or an underlying glomerulopathy. An apparently “obstetric” placental phenotype can therefore be the first clue to maternal renal disease.
2. APS/SLE spectrum
Especially when the degree of placental insufficiency seems disproportionate to maternal clinical findings.
APS is particularly interesting because placental disease can occur even without the mother presenting with classic systemic APS manifestations.
3. Masked chronic hypertension
A normal clinic BP does not completely exclude it. Home or ambulatory BP can reveal nocturnal or intermittent hypertension.
4. Complement-mediated endothelial disease
This is a more unusual but fascinating possibility when placental disease is severe, particularly if there is maternal renal involvement, thrombocytopenia or hemolysis. The phenotype can overlap considerably with preeclampsia/TMA.