“Blood Tests”: The Two Words That Tell You Nothing About Your Prenatal Care
A complete, evidence-based guide to every blood test in pregnancy, when it should happen, and what the evidence actually supports.
The WHO recently published a pregnancy poster listing six “important tests and checks.” One of them was simply: “Blood Tests.” Checkmark. Done. As if drawing blood were a monolithic act, like checking the oil in your car. It is not. There are more than 20 distinct blood tests that may be ordered during pregnancy, each with its own timing, evidence base, sensitivity, specificity, and clinical rationale. Some are among the most strongly evidence-supported interventions in all of medicine. Others are ordered out of habit, with limited data showing they change outcomes. Patients deserve to know which is which.
This is the guide the WHO poster should have been.
Before You’re Even Pregnant: The Ideal Preconception Panel
The best time to draw most of these tests is before conception. A preconception visit should include CBC, blood type and Rh factor, rubella and varicella immunity, hepatitis B and C screening, HIV, syphilis, TSH (yes, preconception is where thyroid screening actually has stronger justification, because you can optimize levels before they affect early fetal brain development), fasting glucose or HbA1c if risk factors for diabetes exist, carrier screening for cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies (and expanded panels if desired), and a urine culture. Vitamin D and ferritin are reasonable additions preconception because you have time to replete before the demands of pregnancy begin. Chlamydia and gonorrhea screening should follow USPSTF guidelines based on age and risk. This is also the time to confirm hepatitis B vaccination status and vaccinate if needed, administer MMR or varicella vaccines if not immune (both are contraindicated once pregnant), and start folic acid supplementation. The tragedy of prenatal care is that too many of these tests are ordered at 8 or 10 weeks, when the window for preconception optimization has already closed. Patients who are planning pregnancy deserve this panel before the pregnancy test turns positive, not after.
First Prenatal Visit (Ideally Before 12 Weeks)
This is where the most blood is drawn. It is also where the most important decisions about your pregnancy care begin. Here is what should be checked and why.
1. Complete Blood Count (CBC)
What it measures: Red blood cells, white blood cells, hemoglobin, hematocrit, platelets, and mean corpuscular volume (MCV).
Why it matters: Anemia in pregnancy is associated with preterm birth, low birth weight, and increased maternal morbidity. The CBC also identifies thrombocytopenia (low platelets), which can signal immune disorders or early preeclampsia, and an elevated MCV, which may point toward folate or B12 deficiency.
Evidence strength: Strong. Universal first-trimester CBC is recommended by ACOG, WHO, NICE, and essentially every major obstetric guideline worldwide. Iron-deficiency anemia affects roughly 15-20% of pregnancies in the U.S. and is treatable. Detecting it early changes outcomes.
What to ask: “What is my hemoglobin? What is my MCV?” If your hemoglobin is below 11 g/dL in the first trimester, you should be evaluated for iron deficiency and treated. If your MCV is elevated (>100 fL), folate or B12 deficiency should be investigated.
2. Blood Type and Rh Factor
What it measures: Your ABO blood type (A, B, AB, or O) and whether you are Rh-positive or Rh-negative.
Why it matters: If you are Rh-negative and your baby is Rh-positive, your immune system can produce antibodies that attack the baby’s red blood cells. This is called Rh alloimmunization, and before the development of RhIg (Rhogam), it was a leading cause of fetal anemia, hydrops, and stillbirth.
Evidence strength: Among the strongest in all of obstetrics. Universal blood typing and Rh testing in pregnancy is one of the great success stories of prenatal care. The introduction of anti-D immune globulin (RhIg) in the 1960s reduced the incidence of Rh disease from approximately 1 in 100 births to fewer than 1 in 10,000. This is a test that has saved hundreds of thousands of lives.
What to ask: “Am I Rh-negative?” If yes, you will receive RhIg at 28 weeks and after delivery (if the baby is Rh-positive). In 2024, ACOG updated guidance to include cell-free fetal DNA testing for fetal RHD genotyping in certain clinical scenarios, potentially allowing targeted rather than universal RhIg administration in Rh-negative women.
3. Antibody Screen (Indirect Coombs Test)
What it measures: Whether you have antibodies against red blood cell antigens other than Rh (such as Kell, Duffy, or Kidd antigens).
Why it matters: Even Rh-positive women can develop antibodies from prior transfusions or pregnancies that can cause hemolytic disease of the fetus. The antibody screen catches these.
Evidence strength: Strong. Universal at first visit. If positive, serial titers and MCA Doppler monitoring are indicated.
4. Rubella Immunity (IgG)
What it measures: Whether you have immunity to rubella (German measles), either through vaccination or prior infection.
Why it matters: Congenital rubella syndrome causes deafness, cataracts, heart defects, and intellectual disability. If you are not immune, you cannot be vaccinated during pregnancy (rubella vaccine is a live vaccine), but you can be vaccinated postpartum.
Evidence strength: Strong for the initial screen. If immunity has been documented in a prior pregnancy, some guidelines (including NICE) consider repeat testing unnecessary. ACOG still recommends testing in each pregnancy. The clinical value of repeat testing in women with documented prior immunity is debatable, since rubella is effectively eliminated in the U.S. (the last endemic case was in 2009). This is a test where the evidence for universal repeat screening is weaker than for the initial screen.
What to ask: “Was I immune last time?” If you were, ask whether repeat testing changes anything. In most cases, it does not.
5. Varicella (Chickenpox) Immunity
What it measures: Whether you are immune to varicella-zoster virus.
Why it matters: Varicella infection in early pregnancy can cause congenital varicella syndrome (limb defects, CNS damage, skin scarring). Infection near delivery can cause severe neonatal varicella. If you have a clear history of chickenpox or vaccination, serologic testing may not be necessary.
Evidence strength: Moderate. ACOG recommends checking immunity if history of disease or vaccination is uncertain. In women with documented vaccination or reliable history of prior infection, testing may be unnecessary.
6. Hepatitis B Surface Antigen (HBsAg)
What it measures: Whether you have an active hepatitis B infection.
Why it matters: Hepatitis B can be transmitted to the baby during delivery. Without intervention, 70-90% of infants born to HBsAg-positive, HBeAg-positive mothers will become chronically infected. With hepatitis B immune globulin and vaccine given to the newborn within 12 hours of birth, transmission drops to below 5%.
Evidence strength: Very strong. Universal prenatal HBsAg screening has been recommended since 1988 and is one of the most cost-effective screening strategies in prenatal care. ACOG’s 2023 guidance additionally recommends hepatitis B triple panel screening (HBsAg, anti-HBs, anti-HBc) for patients without documented negative triple screen after age 18, incomplete vaccine series, or ongoing risk factors.
What to ask: “Have I been vaccinated for hepatitis B, and am I immune?” If not, hepatitis B vaccination is safe and recommended during pregnancy.
7. Hepatitis C Antibody
What it measures: Whether you have been exposed to hepatitis C virus.
Why it matters: Hepatitis C infection during pregnancy carries a 6-7% risk of vertical transmission (higher with HIV co-infection). While treatment with direct-acting antivirals is not yet routinely approved during pregnancy, identification allows for postpartum treatment, infant testing, and appropriate monitoring.
Evidence strength: This is a relatively new universal recommendation. The CDC began recommending universal hepatitis C screening in all pregnant persons during each pregnancy in 2020. ACOG, SMFM, AAFP, and ACNM all endorsed this recommendation. Previously, only risk-based screening was recommended. The change was driven by the rising prevalence of HCV among women of childbearing age, primarily linked to the opioid epidemic and injection drug use.
What to ask: “Was I screened for hepatitis C?” Many practices have added this to their routine prenatal panel, but not all have caught up with the 2020 guideline change.
8. HIV Screening
What it measures: Whether you are infected with human immunodeficiency virus.
Why it matters: Without treatment, mother-to-child HIV transmission occurs in 15-45% of pregnancies. With antiretroviral therapy started during pregnancy, that number drops to below 1%. This is one of the most impactful prenatal interventions in existence.
Evidence strength: Very strong. Universal opt-out HIV screening in pregnancy is recommended by ACOG, CDC, USPSTF, AAP, and WHO. It has been the standard of care for over two decades. Women who decline initial testing should be counseled again and retested in the third trimester. Women at high risk should be rescreened in the third trimester regardless.
9. Syphilis Serology (RPR or VDRL)
What it measures: Whether you have an active or prior syphilis infection.
Why it matters: Untreated syphilis in pregnancy causes congenital syphilis, which can result in stillbirth, neonatal death, prematurity, low birth weight, and severe multi-organ disease. Congenital syphilis cases in the United States increased by 755% between 2012 and 2021. In 2022, the CDC reported that 88% of congenital syphilis cases could have been prevented with timely screening and treatment.
Evidence strength: Very strong, and recently strengthened. As of April 2024, ACOG now recommends universal syphilis screening at three time points during pregnancy: first prenatal visit, third trimester, and at delivery. This replaced the prior risk-based approach for third trimester rescreening. Benzathine penicillin G is the only effective treatment and is safe in pregnancy.
What to ask: “When will I be rescreened for syphilis?” If the answer is “only if you’re at risk,” your provider may not be following the most current guidance.
10. Chlamydia and Gonorrhea Screening
What it measures: These are typically urine-based nucleic acid amplification tests (NAATs) rather than blood tests, but they are often ordered alongside the initial blood panel.
Why it matters: Untreated chlamydia and gonorrhea are associated with preterm birth, premature rupture of membranes, low birth weight, and neonatal conjunctivitis. Chlamydia prevalence in pregnant women under 25 is significant.
Evidence strength: ACOG and USPSTF recommend universal screening for chlamydia in pregnant women under 25 and those with risk factors at any age. Universal gonorrhea screening is recommended for women under 25 and those at increased risk. Repeat testing in the third trimester is recommended for women under 25 or at continued risk.
11. Urinalysis and Urine Culture
What it measures: Again, not a blood test, but universally ordered at the first visit. Screens for asymptomatic bacteriuria, proteinuria, and glucosuria.
Why it matters: Asymptomatic bacteriuria occurs in 2-10% of pregnancies and, if untreated, progresses to pyelonephritis in 20-40% of cases. Pyelonephritis in pregnancy is a serious complication associated with preterm labor and sepsis. Treatment of asymptomatic bacteriuria is one of the few screening interventions with Level A evidence for reducing a specific adverse outcome.
Evidence strength: Very strong for the initial urine culture. Routine dipstick urinalysis at every subsequent visit has much weaker evidence (as discussed in the WHO poster critique).
First Trimester Screening (10-13 Weeks)
12. Cell-Free DNA Screening (cfDNA / NIPT)
What it measures: Fragments of fetal DNA circulating in maternal blood. Screens for trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and sex chromosome aneuploidies.
Why it matters: cfDNA screening is the most sensitive and specific screening test available for common aneuploidies. For trisomy 21, sensitivity exceeds 99% with a false-positive rate below 0.1%. It can be performed as early as 10 weeks.
Evidence strength: Strong for common trisomies. ACOG and SMFM recommend that all pregnant patients be offered screening, including cfDNA, regardless of age or risk. However, critical distinctions apply. cfDNA is a screening test, not a diagnostic test. Positive results require confirmation with CVS or amniocentesis. Expanded panels screening for microdeletions and rare aneuploidies have substantially lower positive predictive values, especially in low-risk populations, and ACOG has stated there is insufficient evidence to recommend cfDNA for single-gene disorders. The commercialization pressure from testing laboratories has outpaced the evidence in some areas.
What to ask: “What exactly is this test screening for, and what is the positive predictive value for each condition in someone my age?” The answer will vary dramatically depending on the condition and your baseline risk.
13. First-Trimester Serum Analytes (PAPP-A and hCG)
What it measures: Pregnancy-associated plasma protein A (PAPP-A) and human chorionic gonadotropin (hCG), combined with nuchal translucency ultrasound.
Why it matters: Combined first-trimester screening detects approximately 82-87% of Down syndrome cases with a 5% false-positive rate. Low PAPP-A is also associated with adverse pregnancy outcomes including growth restriction, preeclampsia, and stillbirth.
Evidence strength: Strong as a screening approach, though increasingly being replaced by or used alongside cfDNA. For patients who decline cfDNA or where cfDNA is unavailable, combined first-trimester screening remains a well-validated option. ACOG recommends that patients have one screening approach and should not have multiple overlapping tests performed independently, as this leads to unacceptably high false-positive rates.
Optional / Risk-Based First-Trimester Tests
14. Thyroid Stimulating Hormone (TSH)
What it measures: Thyroid function.
Why it matters: Overt hypothyroidism in pregnancy is associated with miscarriage, preeclampsia, preterm birth, placental abruption, and impaired neurodevelopment. The question is whether subclinical hypothyroidism matters enough to justify universal screening.
Evidence strength: This is one of the most contested screening questions in obstetrics. ACOG upgraded its recommendation against universal thyroid screening in pregnancy from Level C (expert opinion) to Level A (based on good evidence) in 2015. This was based on three key findings: (1) the association between subclinical hypothyroidism and impaired neurodevelopment is just that, an association, not proven causation; (2) studies on subclinical hypothyroidism and adverse outcomes are mixed; and (3) a large randomized trial of over 21,800 women showed no difference in cognitive function at age 3 in children of women randomized to screening and treatment versus no screening. The American Thyroid Association, by contrast, could not reach consensus and some members advocate for universal screening. A case-finding approach (testing women with symptoms, history, or risk factors) may miss 40-50% of women with thyroid dysfunction.
What to ask: “Do I have risk factors for thyroid disease?” If you have a personal or family history, autoimmune disease, type 1 diabetes, prior thyroid surgery, prior neck radiation, or symptoms suggesting thyroid dysfunction, you should be tested. If you have none of these, the evidence does not support universal screening.
15. Vitamin D Level (25-hydroxyvitamin D)
What it measures: Vitamin D status.
Why it matters: Vitamin D deficiency is common in pregnancy and has been associated with preeclampsia, gestational diabetes, preterm birth, and low birth weight in observational studies.
Evidence strength: Weak for universal screening. ACOG explicitly states there is “insufficient evidence to support a recommendation for screening all pregnant women for vitamin D deficiency” (reaffirmed 2024). For patients at increased risk (dark skin, limited sun exposure, obesity, malabsorption disorders), targeted testing is reasonable. The problem is that while deficiency is common, treatment trials have not consistently shown improvement in pregnancy outcomes.
16. Carrier Screening for Genetic Conditions
What it measures: Whether you carry gene mutations for conditions such as cystic fibrosis, spinal muscular atrophy, sickle cell disease, thalassemias, Tay-Sachs disease, and (with expanded panels) hundreds of additional conditions.
Why it matters: If both parents are carriers for the same autosomal recessive condition, each pregnancy has a 25% chance of being affected. Knowing carrier status allows informed reproductive decision-making, prenatal diagnosis, and preparation.
Evidence strength: Strong for targeted screening. ACOG recommends that all patients be offered carrier screening for cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies. Expanded carrier screening panels testing for 100+ conditions are available and ACOG considers them an acceptable alternative to targeted screening. Ideally, carrier screening is done preconception so that results are available before pregnancy is established. ACMG recommends screening for a panel of conditions with carrier frequency of 1 in 200 or greater.
Second Trimester (15-22 Weeks)
17. Quad Screen (If First-Trimester Screening Not Done)
What it measures: Alpha-fetoprotein (AFP), unconjugated estriol (uE3), hCG, and inhibin A.
Why it matters: This is a second-trimester screening test for trisomy 21, trisomy 18, and open neural tube defects. Detection rate for Down syndrome is approximately 81% with a 5% false-positive rate.
Evidence strength: Well-validated but increasingly being supplanted by cfDNA and first-trimester screening. If cfDNA was performed in the first trimester, a quad screen is generally not indicated. However, maternal serum AFP alone remains valuable for neural tube defect screening, which cfDNA does not assess. Some providers order AFP alone in women who had cfDNA.
18. Glucose Challenge Test (GCT) / Glucose Tolerance Test (GTT)
What it measures: Screening for gestational diabetes. Typically done at 24-28 weeks. In the U.S., the standard two-step approach involves a 50g glucose challenge (non-fasting); if abnormal (>130 or >140 mg/dL, depending on threshold used), a 3-hour 100g oral glucose tolerance test follows.
Why it matters: Gestational diabetes increases risks of macrosomia, birth injury, neonatal hypoglycemia, cesarean delivery, and long-term maternal diabetes.
Evidence strength: Strong for screening. The HAPO study demonstrated a continuous relationship between maternal glucose and adverse outcomes with no clear threshold, which means the diagnosis is partly definitional. Two legitimate screening approaches exist: (1) the two-step approach favored by ACOG (50g screen then 100g GTT) and (2) the one-step approach recommended by WHO and IADPSG (75g fasting OGTT). They use different thresholds and diagnose different proportions of women. A woman can be “normal” under one set of criteria and “diabetic” under another. The ACOG two-step approach has the longer track record in the U.S. The one-step approach diagnoses more women (approximately 15-20% vs. 5-9%) but without clear evidence that treating the additional women improves outcomes.
For women with risk factors (obesity, prior GDM, family history of diabetes, polycystic ovary syndrome), early glucose testing in the first trimester is reasonable.
Third Trimester (28-36 Weeks)
19. Repeat CBC
What it measures: Same as the initial CBC, looking primarily for anemia.
Why it matters: Iron demands increase substantially in the second and third trimesters. Women who were not anemic at the first visit may become anemic.
Evidence strength: Moderate. Widely recommended but the evidence for routine repeat CBC in non-anemic women is not as strong as for the initial test. ACOG recommends repeating the CBC in the third trimester. NICE recommends checking hemoglobin at 28 weeks. If hemoglobin was normal at the first visit and the patient is on iron supplementation, the clinical yield of the repeat test is lower.
20. Repeat Antibody Screen (If Rh-Negative)
What it measures: Whether new antibodies have developed since the first-trimester screen.
Why it matters: This is done at 28 weeks before administering RhIg. If antibodies have already developed, the RhIg will not be effective and the patient needs MFM evaluation.
Evidence strength: Strong for Rh-negative women. This is part of the well-established Rh disease prevention protocol.
21. Repeat Syphilis Screening
What it measures: New syphilis infection acquired since the first test.
Why it matters: As of 2024, ACOG recommends universal rescreening in the third trimester, reflecting the 755% increase in congenital syphilis since 2012.
Evidence strength: Strong. Retrospective studies estimate 25-50% of congenital syphilis cases could be prevented by repeat screening in the third trimester.
22. Repeat HIV Screening (If High Risk)
What it measures: New HIV infection.
Why it matters: Women at high risk (new or multiple partners, injection drug use, partner with HIV) should be rescreened. Some states mandate third-trimester rescreening for all women.
Evidence strength: Strong for high-risk women. The cost-effectiveness of universal third-trimester rescreening in all women depends on local prevalence.
23. Group B Streptococcus (GBS) Culture
What it measures: GBS colonization of the vagina and rectum. This is a swab, not a blood test, but it is often listed alongside third-trimester “labs.”
Why it matters: GBS colonization occurs in approximately 25% of women. Intrapartum antibiotic prophylaxis reduces early-onset neonatal GBS sepsis by approximately 80%.
Evidence strength: Strong. Universal GBS screening at 36-37 weeks (updated from the previous 35-37 weeks) is recommended by ACOG and CDC. Culture-based screening is preferred over rapid intrapartum tests due to higher sensitivity.
At Delivery
24. Repeat Syphilis Screening
What it measures: New infection since the third-trimester screen.
Why it matters: The newest ACOG recommendation (2024). A final check to catch infections acquired late in pregnancy.
25. Cord Blood Type and Direct Coombs (If Mother Is Rh-Negative or Has Antibodies)
What it measures: Baby’s blood type and whether maternal antibodies are attached to the baby’s red blood cells.
Why it matters: Determines whether the baby is at risk for hemolytic disease and whether the mother needs postpartum RhIg.
Tests That Sound Routine But Are NOT Universally Recommended
Thyroid Function Tests
Universal screening: Not recommended (ACOG Level A). Test only with risk factors or symptoms.
Vitamin D
Universal screening: Not recommended (ACOG, reaffirmed 2024). Test only if at increased risk.
Iron Studies (Ferritin, Serum Iron, TIBC)
Not part of routine screening. A CBC with hemoglobin and MCV is the standard screen. Full iron studies are reserved for women with anemia or microcytosis on CBC.
CMV (Cytomegalovirus) Screening
Not recommended universally. No effective prenatal treatment or vaccine exists, and universal screening leads to anxiety without clear benefit.
Toxoplasmosis Screening
Not recommended in the U.S. (recommended in France and some European countries). Low seroprevalence in the U.S. makes universal screening cost-ineffective.
Lead Screening
Not universally recommended. ACOG recommends evaluating risk factors and testing only if a risk factor is identified.
The Problem With “Blood Tests”
When the WHO puts “Blood Tests” on a poster with a blue checkmark, it implies that drawing blood is a single, simple act. It is not. There are at least 25 distinct laboratory evaluations that may be performed during pregnancy, each with its own evidence base, optimal timing, sensitivity, specificity, false-positive rate, and clinical action threshold.
Some of these tests have evidence so strong that failing to perform them constitutes a clear deviation from the standard of care. Universal Rh typing, HBsAg screening, HIV screening, syphilis serology, and CBC fall into this category. These are tests where the evidence has been proven over decades through randomized trials, population-level data, and demonstrable reductions in morbidity and mortality.
Others are recommended by major organizations but have less established evidence for universal application, such as hepatitis C screening (universal only since 2020), third-trimester syphilis rescreening (universal only since 2024), and routine third-trimester CBC in non-anemic women.
Still others are actively debated. Universal thyroid screening is perhaps the best example: ACOG says no (Level A evidence against), the ATA could not reach consensus, and a case-finding approach misses nearly half of affected women. Vitamin D screening has similar uncertainty.
And some tests that many patients believe are “routine” are explicitly not recommended: universal CMV screening, universal toxoplasmosis screening, and universal iron studies beyond a CBC.
Patients have the right to know not just that blood is being drawn, but what it is being tested for, what each test can and cannot detect, and how strong the evidence is behind each one. A checkmark on a poster does not convey any of this.
Know Your Numbers
Here is what every pregnant person should know about their blood work:
Your hemoglobin: Should be above 11 g/dL in the first and third trimesters, above 10.5 g/dL in the second trimester. Below these levels, you have anemia and should be treated.
Your blood type and Rh status: If Rh-negative, you need RhIg at 28 weeks and after delivery.
Your syphilis status: Should be tested three times: first visit, third trimester, and delivery. No exceptions.
Your hepatitis B and C status: Should be screened at the first visit. Every pregnancy.
Your HIV status: Should be tested at the first visit. Period.
Your glucose screen: Should be done at 24-28 weeks, or earlier if you have risk factors.
If any of these were not discussed with you, ask your provider why.
References available upon request. All recommendations cited reflect published guidelines from ACOG, SMFM, CDC, USPSTF, ATA, and WHO as of the most recent updates. No references have been fabricated.