11.3 Medical Disorders & Infections in Pregnancy

Medical Disorders & Infections in Pregnancy

Pre-existing and gestation-induced medical conditions significantly exacerbate maternal morbidity and perinatal mortality. In low- and middle-income settings, managing medical disorders of pregnancy requires clinical officers to balance maternal stabilization with fetal well-being, anticipate disease-specific obstetric crises, and institute timely evidence-based interventions.

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1. Gestational Diabetes Mellitus (GDM)

Gestational Diabetes Mellitus is defined as carbohydrate intolerance resulting in hyperglycemia of variable severity with onset or first recognition during pregnancy. Normal pregnancy is characterized by progressive physiological insulin resistance mediated by placental anti-insulin hormones: Human Placental Lactogen (hPL / human chorionic somatomammotropin), placental growth hormone, cortisol, progesterone, prolactin, and tumor necrosis factor-alpha (TNF-α). These hormones peak between 24 and 28 weeks of gestation, ensuring a continuous supply of glucose across the placenta for fetal growth. GDM develops when maternal pancreatic beta-cells fail to compensate for this pregnancy-induced insulin resistance.

Universal Screening & Diagnostic Criteria

In accordance with WHO (2013) and International Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines, all pregnant women should undergo screening at 24 to 28 weeks of gestation (or at the first antenatal contact if high-risk: BMI ≥ 30 kg/m², prior GDM, previous macrosomic infant ≥ 4.0 kg, polycystic ovary syndrome, or strong family history of type 2 diabetes).

• The Diagnostic Test: 75-gram 2-hour Oral Glucose Tolerance Test (OGTT) performed in the morning after an overnight fast of 8 to 14 hours.
• Diagnostic Cut-Offs (Venous Plasma Glucose): A diagnosis of GDM is confirmed if ANY SINGLE VALUE equals or exceeds the following thresholds:

WHO 75g 2-HOUR OGTT DIAGNOSTIC THRESHOLDS:

• Fasting Plasma Glucose:       ≥ 5.1 mmol/L  (92 mg/dL)
• 1-Hour Post-Load Glucose:     ≥ 10.0 mmol/L (180 mg/dL)
• 2-Hour Post-Load Glucose:     ≥ 8.5 mmol/L  (153 mg/dL)

*Note: If fasting glucose is ≥ 7.0 mmol/L or 2-hour is ≥ 11.1 mmol/L,
it is classified as "Diabetes in Pregnancy" (Overt Pre-existing Diabetes).

Maternal, Fetal & Neonatal Complications

Clinical Management Protocol

1. Medical Nutrition Therapy (MNT): First-line intervention. Caloric distribution: 40–45% complex, low-glycemic-index carbohydrates, 20–25% lean protein, and 30–35% unsaturated fats, distributed over 3 main meals and 2–3 snacks. Moderate exercise (brisk walking 30 minutes daily after meals).
2. Glycemic Monitoring Targets: Fasting plasma glucose ≤ 5.3 mmol/L (95 mg/dL), 1-hour postprandial ≤ 7.8 mmol/L (140 mg/dL), and 2-hour postprandial ≤ 6.7 mmol/L (120 mg/dL).
3. Pharmacotherapy: If glycemic targets are not achieved within 1 to 2 weeks of MNT:
   • Insulin: Gold standard therapy; does not cross the placenta. Combination of basal (NPH or Detemir) and prandial short-acting (Regular or Aspart/Lispro) insulin.
   • Metformin: Acceptable oral alternative where insulin storage (cold-chain) or injection technique is unavailable.

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2. Anemia in Pregnancy

Anemia remains a devastating contributor to maternal mortality in East Africa. During normal pregnancy, maternal plasma volume expands by 40–50% while red blood cell mass increases by only 20–30%, resulting in physiological hemodilution ("hydremia of pregnancy"). Therefore, diagnostic thresholds are lower than in non-pregnant adults.

WHO & Kenya Ministry of Health Diagnostic Thresholds

• Anemia in Pregnancy: Hemoglobin (Hb) < 11.0 g/dL (or Hematocrit < 33%) in the first and third trimesters; Hb < 10.5 g/dL in the second trimester.
• Severity Classification:
  • Mild Anemia: Hb 10.0 to 10.9 g/dL
  • Moderate Anemia: Hb 7.0 to 9.9 g/dL
  • Severe Anemia: Hb < 7.0 g/dL (Hematocrit < 20%)
  • Very Severe / Decompensated Anemia: Hb < 4.0 g/dL (High risk of imminent high-output congestive heart failure and cardiac arrest).

Etiological Factors in Kenya

1. Nutritional Iron Deficiency: Accounts for > 50% of cases due to inadequate dietary intake and depletion of iron stores by the expanding fetal-placental unit (approx 1000 mg total elemental iron requirement across pregnancy).
2. Malaria: P. falciparum causes accelerated hemolysis of parasitized and non-parasitized erythrocytes, combined with cytokine-mediated bone marrow suppression (dyserythropoiesis).
3. Intestinal Helminthiasis: Hookworm infection (Ancylostoma duodenale and Necator americanus) causes insidious, chronic gastrointestinal blood loss.
4. Folate Deficiency: Due to increased cellular turnover and inadequate dietary leafy vegetables.
5. Hemoglobinopathies & HIV Infection: Sickle cell trait/disease and HIV-associated anemia of chronic disease.

Treatment Protocols

ANEMIA CASE MANAGEMENT FLOW:

[Hb 7.0–10.9 g/dL (Mild to Moderate Anemia)]
  • Therapeutic Oral Iron: 120–200 mg elemental iron daily in 2–3 divided doses
    (e.g., Ferrous Sulfate 200 mg TID or Ferrous Fumarate 200 mg BID–TID)
  • Folic Acid: 400 mcg to 5 mg daily
  • Deworming: Albendazole 400 mg single oral dose (after first trimester)
  • Malaria screening: Treat with Artemether-Lumefantrine (AL) if positive
  • Recheck Hb after 4 weeks: Expected rise is ≥ 1.0 g/dL every 2 to 3 weeks
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[Hb < 7.0 g/dL (Severe Anemia) OR Hb < 8.0 g/dL near Term (≥ 36 Weeks)]
  • Mandatory Hospital Admission to Level 4/5 facility
  • Oral iron is INSUFFICIENT due to limited time before delivery
  • Transfuse Packed Red Blood Cells (PRBCs) under cover of IV Furosemide
  • Monitor for Transfusion-Associated Circulatory Overload (TACO)

• Blood Transfusion Rules in Severe Obstetric Anemia:
  • Transfuse Packed Red Blood Cells (PRBCs), not whole blood, to maximize oxygen-carrying capacity while minimizing volume overload.
  • Administer IV Furosemide (20 to 40 mg) with each unit of blood to promote diuresis and prevent lethal pulmonary edema.
  • Infuse very slowly (each unit over 3 to 4 hours) while strictly monitoring respiratory rate, lung bases for crackles, and jugular venous pressure.

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3. Hyperemesis Gravidarum

Hyperemesis Gravidarum (HG) is a severe, intractable form of nausea and vomiting of pregnancy occurring in 0.5–2% of pregnancies. Unlike common "morning sickness" (which resolves by 12–14 weeks without systemic derangement), HG causes progressive dehydration, electrolyte depletion, ketosis, and severe maternal morbidity.

Diagnostic Criteria (Must meet all 4):

1. Persistent, intractable vomiting unrelated to other medical causes, beginning in early pregnancy (< 16 weeks).
2. Significant weight loss: > 5% of pre-pregnancy body weight.
3. Objective signs of dehydration (dry mucous membranes, sunken eyes, skin tenting, orthostatic hypotension, tachycardia).
4. Ketonuria (≥ 2+ on dipstick) with metabolic disturbances (hypokalemic, hypochloremic metabolic alkalosis).

Differential Diagnosis: Always perform a pelvic ultrasound to rule out multiple gestation and hydatidiform mole (molar pregnancy), both of which produce extremely high circulating levels of human chorionic gonadotropin (hCG), predisposing to severe hyperemesis.

The Critical Thiamine Directive & Wernicke's Encephalopathy

CRITICAL SAFETY DIRECTIVE: THE THIAMINE RULE

NEVER ADMINISTER DEXTROSE-CONTAINING INTRAVENOUS FLUIDS
BEFORE OR WITHOUT INTRAVENOUS THIAMINE SUPPLEMENTATION!

• Pathophysiology: Patients with Hyperemesis Gravidarum have depleted hepatic stores
  of water-soluble Thiamine (Vitamin B1). Infusing intravenous dextrose triggers rapid
  intracellular glycolysis, consuming remaining thiamine as a cofactor for pyruvate
  dehydrogenase. This precipitates acute WERNICKE'S ENCEPHALOPATHY.

• Classic Wernicke's Triad:
  1. Acute Mental Confusion / Encephalopathy
  2. Ataxia / Gait Instability
  3. Ophthalmoplegia / Nystagmus / Cranial Nerve VI Palsy

• Consequence of Neglect: Progression to irreversible Korsakoff's Psychosis
  (severe anterograde amnesia and confabulation) or maternal death.

• MANDATORY INTERVENTION: Administer IV Thiamine 100 mg daily for at least 3 days
  PRIOR TO or CONCURRENTLY WITH any dextrose-containing fluids.

Management of Hyperemesis Gravidarum

• Fluid Resuscitation: Start with 0.9% Normal Saline or Ringer's Lactate (1 to 2 liters IV over 2 to 4 hours, then maintenance based on urine output). Add potassium chloride (20–40 mmol/L) once adequate urine output (> 30 mL/hr) is established to correct hypokalemic alkalosis.
• Antiemetic Regimen (Stepwise):
  • Step 1: Pyridoxine (Vitamin B6) 10–25 mg orally/IV three times daily, combined with Doxylamine (10 mg).
  • Step 2: Promethazine (12.5–25 mg IV/IM/oral every 4–6 hours) OR Metoclopramide (10 mg IV/oral every 8 hours).
  • Step 3 (Refractory Cases): Ondansetron (4 to 8 mg IV/oral every 8 hours).

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4. Intrauterine Fetal Death (IUFD) & Disseminated Intravascular Coagulation

Intrauterine Fetal Death (IUFD / Stillbirth) refers to fetal death occurring after the age of viability (in Kenya, defined as gestational age ≥ 28 completed weeks or fetal weight ≥ 1000 g; international guidelines often recognize ≥ 20–24 weeks).

Clinical Presentation & Ultrasound Confirmation

• Clinical Presentation: Maternal complaint of sudden cessation of fetal movements ("baby stopped kicking"), regression of breast fullness and pregnancy symptoms, and symphysis-fundal height lagging behind menstrual dates. On auscultation, fetal heart tones cannot be identified with a Pinard fetoscope or Doppler ultrasound.
• Definitive Diagnosis: Real-time obstetrical ultrasound demonstrating complete absence of fetal cardiac activity and somatic movements.
• Secondary Ultrasound Signs of Maceration:
  • Spalding's Sign: Overlapping of fetal cranial vault bones caused by liquefaction of cerebral tissue and collapse of the intracranial volume (appears 4–7 days post-demise).
  • Robert's Sign: Presence of gas in the fetal great vessels and heart cavities (appears within 48 hours post-demise).
  • Hyperflexion of the fetal spine and collapse of the thoracic cage.

The Pathophysiology of Disseminated Intravascular Coagulation (DIC)

A retained dead fetus is a medical time bomb. When a deceased fetus is retained in utero for longer than 3 to 4 weeks (the "dead fetus syndrome"):

1. Degenerating, necrotic fetal and placental tissues continuously release tissue thromboplastin (tissue factor) into the maternal venous circulation.
2. This triggers massive, generalized activation of the extrinsic coagulation cascade.
3. Microvascular fibrin deposition occurs systemically, consuming maternal platelets, prothrombin, and fibrinogen (consumptive coagulopathy).
4. Secondary fibrinolysis is unleashed, producing high levels of fibrin degradation products (FDPs) and D-dimers, which directly inhibit platelet aggregation and thrombin activity.
5. Clinical Result: Severe hypofibrinogenemia (plasma fibrinogen < 1.5 g/L [150 mg/dL]), severe thrombocytopenia (< 100,000/μL), and catastrophic, uncontrollable maternal hemorrhage from the placental bed, episiotomy sites, venipuncture sites, and mucous membranes during delivery.

Clinical Management Protocol for IUFD

• Laboratory Evaluation: Complete blood count, platelet count, coagulation profile (PT/INR, aPTT, plasma fibrinogen), blood group and crossmatch (minimum 2 units of PRBCs and fresh frozen plasma [FFP] on standby).
• Bedside 20-Minute Whole Blood Clotting Test (Lee-White): Place 2 mL of maternal venous blood in a clean, dry glass tube and leave upright at room temperature. A normal clot forms within 10 minutes and remains solid when inverted. If no clot forms after 20 minutes or a soft clot rapidly lyses, severe hypofibrinogenemia (< 1.5 g/L) is confirmed.
• Induction of Labor: Medical induction of labor is the preferred management once maternal coagulopathy is excluded or corrected. Cesarean delivery is strictly avoided due to severe hemorrhage and infection risks in the presence of dead tissue.
  • Regimen: Vaginal Misoprostol (PGE1) 25 to 50 mcg inserted into the posterior fornix every 4 hours (cautious dosing in scarred uteri), OR mechanical dilation with a transcervical Foley catheter balloon, followed by low-dose IV Oxytocin infusion.
• Anti-D Immunoglobulin: Must be administered (300 mcg IM) to all unsensitized Rh-negative mothers within 72 hours of fetal delivery.
• Bereavement & Compassionate Care: Provide supportive psychological counseling, allow the mother and family to view and hold the infant if desired, and perform a clinical audit to identify the underlying cause (hypertension, infection, cord prolapse, diabetes) to guide future pre-conception planning.