Pregnancy health: essential biomarkers to check before and during pregnancy

Folate, MTHFR, and neural tube development

Folate is the most established nutritional requirement in pregnancy, and for good reason. The first 28 days after conception, often before a pregnancy is confirmed, are the period during which the neural tube closes. Adequate folate is required for this process, and deficiency during this window is a direct cause of neural tube defects including spina bifida and anencephaly. The UK government recommendation to supplement with 400 micrograms of folic acid daily for at least one month before conception and throughout the first trimester reflects this narrow window of greatest need. However, approximately 10 to 25% of people of northern European ancestry carry two copies of the MTHFR C677T variant, which reduces the efficiency of folic acid conversion into its active form by up to 70%. For these individuals, taking methylfolate alongside or instead of folic acid is a more direct way to ensure adequate active folate levels. Testing MTHFR status and homocysteine together before conception identifies whether folate metabolism is genuinely adequate or whether a specific form of supplementation is needed.

Iron and anaemia in pregnancy

Iron demands increase substantially during pregnancy. The body needs iron to support the growth of the placenta, expand maternal blood volume, and supply the developing fetus with the iron required for its own blood formation and brain development. Iron deficiency anaemia affects approximately 15 to 20% of pregnant women in the UK, and when present in the first trimester it is associated with increased risk of preterm birth and low birth weight. Entering pregnancy with confirmed adequate ferritin stores, rather than simply hoping iron is sufficient, is the most reliable approach. Ferritin below 50 ng/mL before conception suggests stores are insufficient to meet the compounding demands of pregnancy without depletion. Building iron stores over three to six months before conception is considerably easier than correcting deficiency during pregnancy, when nausea and digestive changes may limit dietary intake and supplement tolerance.

Thyroid function and pregnancy outcomes

Thyroid disorders are the second most common endocrine condition in pregnant women, after diabetes. The thyroid gland must increase hormone production by approximately 50% during pregnancy to meet fetal demands, as the fetus is entirely dependent on maternal thyroid hormone for the first trimester while its own thyroid gland develops. Women with undiagnosed or poorly controlled hypothyroidism have significantly higher rates of miscarriage, preterm birth, gestational hypertension, and neurodevelopmental delays in the child. The presence of Anti-TPO antibodies, even in women with normal TSH, doubles the risk of pregnancy complications. A full thyroid panel including TSH, Free T4, Free T3, and Anti-TPO antibodies before conception gives time to identify and address thyroid issues before pregnancy places additional demands on thyroid function. The target TSH in the preconception period is generally below 2.5 mIU/L, rather than the general population upper limit of 4.5.

Vitamin D and maternal outcomes

Vitamin D deficiency is associated with increased risk of gestational diabetes, pre-eclampsia, intrauterine growth restriction, and impaired immune function during pregnancy. The developing fetus depends entirely on maternal vitamin D transfer for skeletal development and immune programming. UK guidance recommends supplementing with 400 IU of vitamin D during pregnancy, but this dose may be insufficient to correct established deficiency, which is common in the UK population. Testing 25-OH vitamin D before conception identifies whether supplementation should begin at a corrective or a maintenance dose. A target of above 75 nmol/L before and during pregnancy is supported by the evidence base for optimal maternal and fetal outcomes, rather than simply avoiding clinical deficiency at around 50 nmol/L.

Vitamin B12 and fetal development

Vitamin B12 works alongside folate in the methylation pathway that governs DNA synthesis and cell division throughout pregnancy. B12 deficiency during pregnancy is associated with neural tube defects, low birth weight, and impaired fetal brain development. Women following plant-based diets, those who have been on the oral contraceptive pill for several years, or those with any digestive condition affecting B12 absorption are at particular risk. Testing B12 and homocysteine together reveals whether the methylation pathway is functioning adequately: elevated homocysteine alongside borderline B12 indicates a functional deficiency even when serum B12 appears technically normal.

Blood glucose and gestational diabetes risk

Gestational diabetes affects approximately 5 to 10% of pregnancies in the UK and is associated with a higher risk of complications for both mother and baby including large for gestational age infants, birth complications, and increased lifetime risk of type 2 diabetes in the mother. HbA1c before conception reveals pre-existing blood glucose patterns and identifies women at elevated risk. A woman entering pregnancy with HbA1c in the high-normal range (approaching 42 mmol/mol) is at significantly higher risk of developing gestational diabetes than one with optimal metabolic health. Testing and improving HbA1c before conception, through dietary changes and lifestyle intervention, is more effective than managing gestational diabetes once it has developed.

Homocysteine and pregnancy complications

Elevated homocysteine is associated with increased risk of neural tube defects, pre-eclampsia, placental abruption, and intrauterine growth restriction. It reflects impaired function of the folate and B12 methylation pathway. Homocysteine levels above 15 micromol/L in the preconception period are a signal to optimise folate and B12 status before conception. Importantly, homocysteine can be elevated in the presence of technically normal serum folate and B12 if the MTHFR enzyme is impaired or if functional deficiency exists at the cellular level. Testing homocysteine directly, rather than inferring methylation adequacy from individual nutrient levels, gives the most accurate picture of whether the pathway is genuinely functioning.

The standard NHS antenatal booking appointment tests haemoglobin, blood type, rubella immunity, hepatitis B, HIV, syphilis, and urine protein. Nutritional status, thyroid function beyond TSH, and metabolic health are not routinely included. This creates a significant gap between the tests offered and the biomarkers that most influence pregnancy outcomes.

A comprehensive preconception and pregnancy biomarker panel should include:

TSH, Free T4, Free T3, and Anti-TPO antibodies give the complete thyroid picture. This is particularly important given the 50% increase in thyroid hormone demand during pregnancy and the significant impact of thyroid antibodies on miscarriage risk.

Homocysteine and folate together reveal whether the methylation pathway is functioning adequately. These are more informative in combination than either marker alone.

Vitamin B12 is essential for DNA synthesis throughout pregnancy. Testing before conception identifies deficiency while there is time to correct it.

Ferritin reveals iron stores. Optimising ferritin before conception is the most effective way to ensure iron adequacy throughout pregnancy.

Vitamin D (25-OH) should be tested before conception and potentially retested in the second trimester to ensure levels remain adequate as fetal demands increase.

HbA1c provides a three-month blood glucose picture. High-normal HbA1c before conception is an actionable risk factor for gestational diabetes.

CRP reveals whether chronic inflammation is present that may affect implantation or placental function.

MTHFR genetic testing clarifies which form of folate supplementation is most appropriate for your genetics.

Preconception testing is most valuable ideally three to six months before actively trying to conceive, giving sufficient time to correct identified deficiencies before the critical early developmental window. Testing during pregnancy, particularly in the first and second trimesters, allows ongoing monitoring of the markers that change most significantly under pregnancy's physiological demands.

Start folate and B12 before conception

The neural tube closes in the first 28 days of pregnancy, often before a confirmed positive test. Beginning folate supplementation at least one month before trying to conceive, and ideally three months before, ensures adequate levels are present during this critical window. For women with MTHFR variants, switching from folic acid to methylfolate, the bioavailable active form, ensures that the supplement bypasses the impaired conversion step. Testing homocysteine three months after starting supplementation confirms whether the intervention is producing the expected reduction in homocysteine levels.

Build iron stores ahead of pregnancy

A 12-week course of dietary iron optimisation or supplementation before conception can meaningfully raise ferritin levels. Animal sources of haem iron (red meat, liver) are considerably more bioavailable than plant sources, but non-haem iron from legumes, dark leafy greens, and fortified foods is meaningfully absorbed when eaten alongside vitamin C. Retesting ferritin after two to three months of dietary intervention confirms whether levels have improved sufficiently. The target is ferritin above 50 ng/mL before conception, with awareness that levels will decline during pregnancy regardless of how well iron intake is managed.

Correct vitamin D before the first trimester

Vitamin D deficiency typically takes three to four months of supplementation to correct, depending on the starting level and the dose. UK adults deficient in vitamin D (below 50 nmol/L) generally require 2000 to 4000 IU daily to correct deficiency rather than the standard 400 IU maintenance dose. Testing before starting a correction protocol establishes the baseline and allows the dose to be calibrated appropriately, with retesting after three months confirming whether the target has been reached before or during early pregnancy.

Manage blood glucose before conception

Improving insulin sensitivity and blood glucose stability in the months before conception reduces the risk of gestational diabetes and its associated complications. The most effective dietary strategies include reducing refined carbohydrate and sugar intake, increasing dietary fibre, maintaining protein intake, and eating regular structured meals rather than irregular high-carbohydrate patterns. Tracking HbA1c every three months gives an objective measure of whether dietary and lifestyle changes are producing the expected metabolic improvement. A meaningful improvement in HbA1c before conception reduces the gestational diabetes risk and improves the hormonal environment for implantation.