Zinc selenite

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: case report

Adequacy of study:

supporting study

Study period:

no information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: case report

Data source

Reference

Reference Type:

publication

Title:

Chronic exposure to high doses of selenium in the first trimester of pregnancy: Case report and brief literature review

Author:

D'Oria, L. et al.

Year:

2018

Bibliographic source:

Birth Defects Research. 2018;110:372–375.

Materials and methods

Study type:

poisoning incident

Endpoint addressed:

repeated dose toxicity: oral

developmental toxicity / teratogenicity

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

A pregnant woman received 200,000 µg per day of a selenium galenic formulation, since gestational week (g.w.) 7 to 12, due to a prescription error (intended dose: 200 µg per day).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

selenium (unspecified)

IUPAC Name:

selenium (unspecified)

Details on test material:

No further information on substance stated.

Specific details on test material used for the study:

selenium supplement using a galenic formulation, a tablet with a dose of 200,000 µg of selenium per day

Method

Type of population:

general

Subjects:

41-year old pregnant woman, who had a normal pregnancy, despite hypothyroidism that was treated with levothyroxine 25 µg per day.

Ethical approval:

not applicable

Route of exposure:

oral

Reason of exposure:

other: intentional, but overdosed due to a prescription error

Exposure assessment:

not specified

Details on exposure:

Because of a mild asthenia and as an adjuvant regarding the thyroid function, the obstetrician prescribed a selenium supplement using a galenic formulation. Due to a prescription error, the patient received a tablet with a dose of 200,000 µg of selenium per day instead of 200 µg per day, from g.w. 7 to 12. The mistake was discovered by another pharmacist, to whom the drug formulation was provided.

Examinations:

Mother: Selenium plasmatic levels at gestational week (g.w.) 15, 21, 25, 30 and 36; electrocardiogram at g.w. 17; monthly ultrasound scans; at birth, a sample of the cord blood was taken to evaluate the blood pH and cord selenium.
Child: The baby underwent blood tests; neurological examination; reflex evaluation and audiological screening; cerebral ultrasound (third day of life), at 2 months of age; the infant underwent a renal ultrasound and echocardiography.

Medical treatment:

not specified

Results and discussion

Clinical signs:

About one week after the treatment, the patient was affected by nausea, vomiting and significant weakness, but related these symptoms to the pregnancy. Consequently, the woman experienced hand and foot paresthesia, inability to concentrate and loss of the fingernails and scalp hair.
Two weeks after stopping selenium intake, the woman reported no nausea and reduced paresthesia. Inability to concentrate and asthenia persisted for 6 weeks.

Results of examinations:

Selenium plasmatic levels at g.w. 15, 3 weeks after arrest were 307.5 µg/L, while urinary selenium levels were 29.0 µg/L. Normal values are considered lower than 130 µg/L in the blood and lower than 70 µg/L in the urine. The electrocardiogram at g.w. 17 (4 weeks after arrest) was normal. Early amniocentesis performed for maternal age reported a normal female karyotype result. Monthly ultrasound scans were carried out to assess the fetal condition. No morphological abnormalities were detected and the maternal Doppler evaluation showed an increased uterine artery vascular flow resistance. The patient underwent regular pregnancy check-ups, and every 4–5 weeks selenium concentration was monitored in the plasma and urine. These results are reported in Table 1 (see any other information on results incl. tables). A cesarean section was performed at g.w. 39 for previous myomectomy. The woman delivered a living female neonate with a birth weight of 3300 g. and an Apgar score of 9 at the first and the 10th minute. At birth, a sample of the cord blood was taken to evaluate the blood pH and cord selenium. The pH cord blood value was normal (pH=7.3) and the selenium umbilical cord concentration was 58.1 µg/L. The baby underwent blood tests which revealed normal electrolytes, creatinine, transaminases, glucose, and blood urea nitrogen. The neurological examination was normal, and the reflex evaluation and audiological screening (Transient Evoked Otoacoustic Emissions) were negative. The cerebral ultrasound performed on the third day of life, did not detect any abnormality, and the newborn was discharged on the fourth day after delivery. At 2 months of age, the infant underwent a renal ultrasound and echocardiography, which were both normal, and a 3-month follow-up after delivery showed that the infant was developing normally.

Effectivity of medical treatment:

not specified

Outcome of incidence:

Maternal selenium levels in the blood were still high three weeks after arrest and reached a normal range 13 weeks after arrest. Subsequently, selenium levels remained stable until the end of pregnancy. On the contrary, urinary output did not seem to be influenced by the serum selenium levels and remained normal. The levels of selenium in the cord blood at birth were about half compared to those in the maternal blood. Overall, no consequences of congenital defects or pregnancy complications occurred.

Any other information on results incl. tables

Table 1. ^a Normal serum values <130 µg/L. ^b Normal urine values <70 µg/L

Gestational age	Serum selenium^a (µg/L)	Urinary selenium^b (µg/L)
g.w. 15	307.5	29
g.w. 21	194.8	14.6
g.w. 25	116.9	13.5
g.w. 30	127.1	19.4
g.w. 36	110.3	27.4

Applicant's summary and conclusion

Conclusions:

One patient (pregnant woman) who received high daily doses of selenium due to a prescription error over a certain period of time experienced nausea, vomiting, paraesthesia of hands and feet, followed by fatigue, loss of fingernails and hair.
This single case does not allow us to draw conclusions on the effects of high doses of selenium on the fetus. The authors suggested however, considering the high doses received and the absence of side effects on the fetus, one could hypothesize that the placenta can prevent an excessive transfer of selenium to the fetus.

Executive summary:

A pregnant woman received 200,000 µg per day of a selenium galenic formulation, since gestational week (g.w.) 7 to 12, due to a prescription error.

The patient experienced nausea, vomiting, hand and foot paresthesia, followed by fatigue, loss of fingernails and hair. The woman was referred to the Fetal and Maternal Medicine Unit for surveillance. The mother’s blood selenium levels went back to normal 13 weeks after arrest and the baby was born at term, without complications. Clinical evaluation and imaging studies were normal at one month of age.

This has been the first case of severe chronic selenium intoxication during the first trimester of pregnancy. In the present case, no consequences of congenital defects or pregnancy complications occurred.