Pregnancy Blood Tests in the Second Trimester

It’s the second trimester. Your patient’s morning sickness has hopefully subsided, and she’s feeling great. The only problem is that her alkaline phosphatase is increased while her gamma-glutamyl transferase (GGT) is decreased. You know that decreased GGT usually indicates hypothyroidism or magnesium deficiency, two critical considerations in pregnancy.  

What’s going on? 

In the first blog in this series, we outlined how pregnancy blood tests begin to shift in the first trimester. 

In this blog, we’ll explore changes specific to the second trimester. 

The bottom line? Pregnancy ranges are much, much different than the now-popular functional ranges.

The example above of increased alkaline phosphatase and decreased GGT in the second trimester? These are completely normal patterns in the second trimester and more than likely don’t indicate any abnormalities.

Pregnancy blood tests reflect physiological changes

Recall the extensive physical changes listed in the first blog: enlarged pituitary and thyroid glands, increases in leptin, ghrelin, and insulin, and adaptations from every system in the body to accommodate the health of the parent and the growing fetus. 

In the second trimester, insulin resistance begins, along with further shifts in thyroid function, adrenal function, and kidney function and size. Blood pressure and glucose levels slightly drop. Serum cholesterol and triglycerides rise (1). 

As pregnancy evolves, so does the need to interpret blood chemistry results according to trimester. 

Keep reading to learn the specific markers you should be aware of in your second-trimester patients.

Pregnancy blood tests: A bioindividual interpretation

Insulin

As stated in the title of this paper, normal pregnancy is a state of insulin resistance.

One of the major hematological changes in the second trimester is an expected increase in serum insulin. While glucose levels do not dramatically change from trimester to trimester, insulin begins to increase in the first trimester and gradually rises throughout pregnancy to levels approximately 60% higher than non-pregnant levels. 

Why? 

With the help of hormonal surges of estrogen, progesterone, and human placental lactogen, the mother’s body begins resisting the actions of insulin in order to shuttle glucose away from her cells to the very glucose-hungry cells of the fetus. 

The fetus metabolizes the more energy-efficient glucose (2), while the mother relies on fat for the creation of ATP.

So, pregnancy blood tests for insulin and c-peptide will reflect this metabolic shift.

Second-trimester takeaway: Be aware that serum insulin may be increased by approximately 29% from pre-pregnancy levels.

Bilirubin

Pregnancy blood tests reflect decreases in direct (conjugated) and total (combination of conjugated and unconjugated, or free) bilirubin in the second trimester.

The reason behind this drop is more than likely due to the hemodilution described in part one of this blog series. 

Essentially, hormonal changes in pregnancy increase blood plasma volume. Due to this increase in volume, the carrier protein for bilirubin, albumin, becomes diluted, and bilirubin levels decline (3). 

However, keep a close watch on bilirubin levels that drop too low, especially in women with pre-eclampsia. The optimal reference range for the second trimester is 0.1 – 0.8 mg/dl (4). Levels lower than this are strongly related to adverse outcomes in those with pre-eclampsia, such as requiring a cesarean section due to fetal distress (5).

Second-trimester takeaway: All forms of bilirubin decrease by the second trimester, but be aware of levels that drop too low in women with pre-eclampsia. 

Gamma-glutamyl transferase (GGT)

While GGT levels in the first trimester don’t significantly differ from those of non-pregnant females, they do begin to decrease in the second trimester. 

This may be due to the influence of continually rising sex hormones on liver function paired with blood dilution from rising plasma blood volume (6).

In non-pregnant people, the liver enzymes AST and ALT are often run along with GGT to learn more about the overall health of the liver. Increases in these enzymes can signal non-alcoholic fatty liver disease, hepatitis, insulin resistance, and oxidative stress. 

An increase in pre-pregnancy GGT, specifically, may indicate a higher risk of gestational diabetes mellitus in subsequent pregnancies. (7) Mid-pregnancy increases in GGT can also point toward the development of gestational diabetes as pregnancy progresses (8).  

So, be aware of increasing levels versus the physiologically normal occurrence of decreased levels during pregnancy. And be sure to refer to the first blog in the series for the specific pattern of increased GGT, alkaline phosphatase, and uric acid that is linked to gestational hypertension and pre-eclampsia.

 Second-trimester takeaway: GGT begins to decrease by the second trimester—if levels increase, monitor closely for the possible development of gestational diabetes mellitus.

Blood urea nitrogen (BUN), creatinine, glomerular filtration rate (eGFR), sodium, & potassium

The physiology and anatomy of the kidneys change dramatically in pregnancy, so much so that one paper called it a “physiologic feat” (9)! 

The length and volume of the organs increase by about 1.5 centimeters due to fluid retention, while eGFR increases by 50% compared to non-pregnant levels.

One of the most dramatic changes during pregnancy is the increase in sodium reabsorption. However, the water retention that occurs during pregnancy is proportionally greater than the sodium retention. Therefore, plasma sodium concentrations actually decrease.

BUN, creatinine, and potassium also begin to decrease by the second trimester. Additionally, blood pressure drops by approximately 10 mmHg in mid-pregnancy. 

As you may have guessed, the major driver of these shifts is likely the hemodilution described above. The interplay of increased levels of human chorionic gonadotropin, estrogen, progesterone, and relaxin during pregnancy signals blood volume expansion and leads to vasodilation. 

These adjustments occur in tandem with the renin-angiotensin-aldosterone system (RAAS), the major regulator of blood pressure and systemic electrolyte and fluid balance—the RAAS is influenced by the rise in pregnancy hormones. 

However, RAAS hormones, like renin, also increase during the second trimester due to release from organs other than the kidneys, such as the ovaries, uterus, and placenta. 

Second-trimester takeaway: eGFR increases while BUN, creatinine, uric acid, sodium, potassium, and blood pressure decrease.

Pregnancy blood tests continue changing from the first trimester

Most pregnancy blood tests continue to fluctuate from the first to the second trimester. 

These include: 

• further increases in alkaline phosphatase
• further relative decreases in red blood cells
• both increases and decreases in thyroid hormones, including slight increases in free T4 and free T3 in the first trimester and slight decreases in the second trimester

Automate your interpretation of pregnancy blood tests

If you’re looking for a way to speed up your research-backed interpretation of pregnancy blood tests, we can help. 

LabSmarts accounts for multiple blood test outcomes affected by pregnancy—you can keep seeing patients (and spending time with your family) while our software does the work.

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928162
2. https://www.ncbi.nlm.nih.gov/books/NBK26882
3. https://www.ncbi.nlm.nih.gov/books/NBK6005
4. https://www.perinatology.com/Reference/Reference%20Ranges/Bilirubin,total.htm
5. https://www.sciencedirect.com/science/article/abs/pii/S0301211513002558
6. https://www.ncbi.nlm.nih.gov/books/NBK6005
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067389
8. https://pubmed.ncbi.nlm.nih.gov/29385633
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089195