Pregnancy and Fetal Testing

There are specific markers that correlate to normal or abnormal fetal health that are important to know. Its also important to understand the normal course of a pregnancy and also the normal circadian rhythm of hormones that are involved in ovulation and a womens’ menstrual cycle. Both the anterior pituitary and ovaries are involved in secreting hormones to control menstruation and pregnancy.

Menstruation

A womens’ menstruation cycle is typically 28 days consisting of a follicular phase and a luteal phase followed by menses. Ovulation occurs around the 14 day mark and lasts for a short 24 hours. Ovulation is also the peak of the follicular phase and the start of the luteal phase.

The anterior pituitary secretes luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during menstruation. During the follicular phase before ovulation both LH and FSH are pretty stagnant, meaning that there is no elevation or decrease in levels for these hormones. Once ovulation starts both LH and FSH dramatically increase, but the ratio between LH and FSH is skewed towards a higher elevation in LH. These hormones remain elevated for the 24 hours that ovulation is occurring then level back out after for the remainder of the luteal phase and menstruation.

The ovarian cycle is very important. There is a growing follicle during the follicular phase. During ovulation, the ovaries release and egg that implants itself into the uterine wall waiting to be inoculated by sperm. When ovulation is over the follicle continues to the corpus luteal and eventually the corpus albicans at the peak of the luteal phase before menses. During the follicular phase (0-14 days) the ovaries are primarily secreting estradiol in increasing levels. During ovulation estradiol drops dramatically and the secretion of progesterone rapidly increases. For the remainder of ovulation and the luteal phase (15-28 days) progesterone remains elevated and estradiol recovers some.

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Another important topic to touch on just briefly is the physiology of oral contraceptives. Normally in the luteal phase, after ovulation has concluded there are low levels of the pituitary hormones LH and FSH and elevated levels of estradiol and progesterone. Oral contraceptives are an attempt to mimic the luteal phase so ovulation can’t occur. They contain high levels of progestogens and estrogen that block the feedback loop to the pituitary to secrete LH and FSH.

Pregnancy Testing

There are three trimesters in pregnancy. The first trimester is from 0-12 weeks, the second from 13-28 weeks, and the third being 29-40 weeks. The placenta is responsible for respiration and excretion in the growing fetus. Carbon dioxide and metabolic waste diffuse from fetus to the mother, and oxygen and nutrients pass from the mother to the fetus. Routine testing for a mother who is pregnant may include a blood test, urine tests, blood pressure, fetal heartbeat, and a complex medical examination to determine whether the pregnancy is progressing as it should and the mother and fetus are healthy.

The blood sample is analyzed for rubella. Rubella can be dangerous to the fetus, causing brain damage and deafness, which is why its important to always vaccinate. Blood sugar is measured as a risk for gestational diabetes. STIs are looked for. The mothers Rh blood group factor is measured to indicate whether the fetus is at risk for hemolytic disease of the fetus and newborn (HDFN). The mother is also tested for HIV as that can cross the placenta and infect the fetus.

The urine is analyzed for protein (primarily albumin) which can be a sign for infection. Glucose is measured again as an indicator for gestational diabetes.

Screening tests such as an ultrasound, Nuchal translucency test, AFP and serum screening are done for assessment of the chances of having a fetus with spina bifida or downs syndrome.

The Nuchal Fold Translucency Test is done with an ultrasound and involves measuring the amount of skin on the fold of the fetus neck as it is thicker in babies who have Downs syndrome. Its important to note that this alone DOES NOT mean that this doesn’t indicate Downs syndrome. Its just one risk factor.

Human chorionic gonadotropin (hCG) is released by the placenta and it maintains the endometrium. It induces the production of progesterone until the placenta can do so itself around the 2nd trimester. Its important to note that pregnancy testing is based on the beta subunit of hCG in urine OR in the serum. It is much more concentrated in the blood. hCG can be detected as early as eight days after ovulation and even one day after implantation. During the pregnancy hCG doubles about every two days for the 2-5 weeks and peaks around 10 weeks. There are two types of pregnancy tests that utilize hCG as a marker. The at home point-of-care pregnancy tests are qualitative. They give a yes/no result and is typically done with urine. Quantitative testing can be done on either the serum or urine and gives a numerical result of the b-hCG. Doctors may order a quantitative test for an evaluation of either an ectopic or failing pregnancy which shows a decreased rate of increase in hCG.

Alphafetoprotein (AFP) is usually done between the 15th and 18th week of gestation. AFP is a a-feto protein produced by the fetal liver and is released into amniotic fluid and appears in the maternal serum. levels of AFP are relatively NONSPECIFIC and an increase could indicate that the individual is actually farther along than initially thought. It could indicate that there may be more than one fetus, and in rare cases can indicate Spina Bifida. Low AFP in contrast means that the individual is not as far along as previously thought. It can also indicate that the baby may have Downs syndrome.

Serum screening is also known as the Triple Test of Bart’s test. This measures the blood levels of AFP, bhCG, E3 (Estriol), and inhibin-A in an attempt to identify the risk of Downs Syndrome or neural tube defects.

A low AFP, low Estriol (E3), elevated hCG, and elevated inhibin-A  is associated with Downs Syndrome.

A low AFP, low E3, and low hCG is associated with Trisomy 18 (Edwards Syndrome).

A elevated AFP is associated with a neural tube defect such as Spina Bifida.

Inhibin-A appears to be involved in the control of follicular development through negative feedback regulation of FSH.

PAPP-A (Pregnancy associated plasma protein A) is a zinc metalloproteinase. This is not always measured, but low levels at week 10-14 can indicate Downs Syndrome.

Feta fibronectin (fFN) is a glycoprotein that works to attach the fetal sac to the uterine wall. It works like glue. The presence of fFN in crevice-vaginal secretions during weeks 22-35 of gestation indicates an increased risk of preterm delivery.

The lecithin/sphingomyelin (L/S) ratio is the most valuable assay for the assessment of fetal pulmonary maturity. Typically at gestational week 32 the L/S ratio is 1.0. At 35 weeks the L/S reaches 2.0. A ratio of greater than 2.0 and continuing to rise means that pulmonary maturity has occurred.

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