Foetal Development and Placental Transfer

• The learning outcomes are to understand common ailments during pregnancy, know how to respond to symptoms, and be aware of teratogenicity and how some medicines affect foetal development.

Conception Timing

• Pregnancy is calculated from the first day of the last menstrual period (menstrual age), about 2 weeks before conception actually occurs.
• Conception date might be the day sex occurred or later, since sperm can live up to 5 days.

Foetal Development Stages

• From 4 weeks the foetus is the size of a poppy seed, to 12 weeks when the foetus is the size of a lime
• From 13 weeks the foetus is the size of a lemon, to 24 weeks when the foetus is the size of Corn
• From 28 weeks the foetus is the size of an eggplant, to 40 weeks when the foetus is the size of a watermelon.
• Three distinct stages are included:
• Blastocyst formation takes 0-16 days after conception
• Organogenesis takes 17-60 days entailing cell division, migration, differentiation and cell death.
• Histogenesis & functional maturation takes place from 61 days until full term
• Average pregnancy is 280 days/40 weeks, but foetal viability is possible at 22 weeks.

Trimesters of Pregnancy

• Each trimester lasts 13-14 weeks
• Maternal weight gain is approximately 11-14kg.
• First trimester increases blood volume, uterine and breast size
• Second trimester increases deposition of fat stores
• Third trimester increases foetal and placental growth.
• Physiological changes occur in different systems, like increased heart rate and decreased blood pressure, gastric acid secretion and emptying and bladder capacity changes.
• Accidental exposure to drugs or chemicals can occur if a woman is unaware of being pregnant.

Route of Transfer

• Placenta's function, is respiratory (gas exchange), excretory (water and pH balance), and resorptive
• Lipid-soluble drugs, with low Mwt and are lipophilic/non-ionized, can pass through the placenta though it can act as a barrier.
• Transfer across placenta is determined by concentration gradient between foetal and maternal circulation via passive diffusion of free non-ionized molecules.

Placental Transfer Classifications

• Quantity of drug reaching foetus depends on molecule's physio-chemical characteristics and maternal pharmacokinetic parameters (varies).
• High transfer means drugs cross rapidly, with foetal concentration close to maternal pharmacological concentration at equilibrium.
• Limited transfer means foetal concentration is lower than maternal concentration.
• Excess transfer means foetal concentration is higher than maternal, with limited retro-passage to maternal circulation.
• Pituitary hormones, insulin, and TSH don't cross at all.

Prescribing in Pregnancy

• Potential harm must be weighed against benefit for foetus or mother.
• Drug therapy may arise from pre-existing medical conditions or pregnancy related complication.
• 'Least harmful' therapy should be chosen, lowest dose, dosage intervals/frequency.

Factors to Consider in Prescribing

• Maternal factors, like, implications of not taking the drug, maternal choice, gestation and co-morbidities
• Foetal factors include risk of congenital malformations (especially in weeks 1-8), organ toxicity and withdrawal postpartum
• Drug factors like altered absorption, distribution, metabolism and excretion, narrow therapeutic index, safer alternative, and ability to cross placenta.

Common Ailments in Community Pharmacy

• These include Nausea and vomiting (morning sickness), haemorrhoids, indigestion/acid reflux, UTIs/thrush, and anaemia.

Morning Sickness

• This presents as Nausea & Vomiting in 70-80% of all pregnant women
• It happens usually 4-8 weeks gestation, and rarely after 16 weeks
• Severe form is hyperemesis gravidarum which presents as persistent nausea, weight loss, appetite reduction, dehydration with risk of starvation
• Hormonal disturbances, along with neurological and physical factors are causes of condition
• Treatment is by anti-emetics (usually POMs), so refer to GP.

Constipation & Haemorrhoids

• Constipation afflicts 10-30% pregnancies and includes motility of smooth muscle caused by progesterone.
• Food passes through the GIT slowly also as activity decreases.
• Laxatives relieve constipation though stimulant laxatives should be avoided, especially in later stages.
• Haemorrhoids are caused by enlarged uterus exerting pressure and blood volume leading to venous dilation and engorgement causing itching and bleeding.

Indigestion

• Indigestion happens is more than 25% of pregnancies, usually 3rd Trimester
• Belching, nausea and a bloated feeling are characteristics
• Also includes Reflux of stomach acid, which is worse when eating, lying or bending over.
• Physical measures like small frequent meals and elevation on top of bed, and avoiding certain foods help treat condition
• Antacids + alginate alleviates condition
• Al or Mg containing antacids are used on an ‘as required' basis.

Thrush

• This is a fungal infection caused by candida albicans.
• Opportunistic infection is caused by hormonal changes altering the vaginal environment.
• Topical agents, e.g. clotrimazole can be used though it is best to refer if oral treatment is likely
• Natural yoghurt with acidophilus can be inserted into vagina

Urinary Tract Infection

• The conditions are very common during pregnancy
• Involves growing foetus putting pressure on the bladder and urinary tract, which traps bacteria or leads to urine leak.
• Do not treat OTC, rather refer to GP for possible antibiotic prescription

Anaemia

• Iron deficiency can cause anaemia with spontaneous abortion, premature delivery, low birth weight infant.
• Iron supplements, variety of doses, usually 200mg FeSO4 or other iron salts alleviates condition

Common Conditions Experienced During Pregnancy

• This includes hypertension and pre-eclampsia, gestational diabetes, venous thromboembolism (VTE) and Obstetric cholestasis.
• These are not for management in Community Pharmacy and should be referred to Primary Care / GP.

Teratogenicity

• A teratogen, is a substance, organism or process that causes malformations in a foetus (congenital abnormalities).
• These are unethical to research using RCTs, so are investigated via epidemiological studies with anecdotal evidence/experience
• Relatively small number of implicated drugs, infections/viruses, genes and environmental factors such as lead.
• There are structural and behavioural effects, for a full list check individual monograph in the BNF or the drugs SPC.

Major Teratogenic Drugs in Humans

• Organ formation occurs in the first 3 months of pregnancy, therefore teratogenic drugs taken in this period tend to cause structural defects.
• From 3 months onwards, teratogenic drugs tend to cause growth defects.
• The major dugs include, Alcohol, Warfarin, Lithium, Valproic acid, Carbamazepine, 6-mercaptopurine, Methotrexate, Cyclophosphamide, Androgens, 19-Norsteroids, Isotretinoin, Acitretin and Thalidomide

FDA Categories

• FDA previously used A, B, C, D. or X categories though this left to false assumption about the actual meaning of the letters
• 'A' means the drug is well-studied and poses no threat to a developing baby
• 'B' means the drug is less-studied, though is probably still low-risk
• 'C' means drug not studied and therefore the risk is unknown
• 'D' means based on animal or human data, may pose a risk.

Breast Feeding

• Insufficient evidence exists though it is advisable to administer only essential drugs to a mother during breast feeding
• Use drugs with short half life and feed just before mother takes medication
• Lipid soluble drugs diffuse into breast milk and concentrate high fat content of milk.
• Quantity/conc of drug is generally too small to affect baby

Ethical Considerations

• Ethical choices include whether to medicate or not, which would depend on risk benefit ratio, and which medicine is best.
• Biases must be addressed.