Chelation during sequential pregnancies: A case report with a twist

Abstract

This report summarizes chelation management of lead poisoning occurring during sequential pregnancies. Several aspects make this case unusual; firstly recurrent lead poisoning, secondly treatment with succimer, the use of which is very rarely reported in pregnancy, and thirdly the presence of co-existent vitamin D deficiency and hyperparathyroidism, both potential contributors to bone lead release.

Case

An asymptomatic 28-year-old woman was found to have a blood lead level (BLL) of 49 µg/dL during her third trimester of her second pregnancy, identified by routine screening initiated by primary care providers. Six months earlier, a routine screening test had found a BLL of 13 µg/dL. No interval BLLs were obtained.

She was admitted for five days of chelation therapy with intravenous CaNa₂EDTA (also known as calcium disodium edetate or versenate). However, this drug was not initially available. Oral succimer was substituted for 1.5 days until the arrival of the CaNa₂EDTA. Both drugs were well tolerated at standard doses. On day 6, at the end of chelation, her BLL troughed at 24 µg/dL. At delivery one month later her BLL rebounded to 36 µg/dL. The cord BLL was 50 µg/dL so the baby received a five-day course of chelation with succimer. The woman was also noted to have elevated serum calcium and parathyroid hormone (PTH) levels and was found to have vitamin D deficiency. Ultrasound imaging of the neck and kidneys was normal. The high pretreatment BLLs meant a rebound was anticipated, therefore she was advised not to breastfeed initially.

This was her second referral for lead poisoning during pregnancy. During her second trimester of her first pregnancy a screening BLL was 18 µg/dL. Two months later her BLL had increased to 53 µg/dL. At that time she had been admitted and received a 5-day course of intravenous CaNa₂EDTA. Post-chelation her BLL troughed at 21 µg/dL. At delivery one month later her BLL was 28 µg/dL and her newborn’s cord BLL was 29 µg/dL.

She was born in Mexico and has been living in the USA for an unspecified duration. At the time of her first pregnancy, no lead paint violations were found in her home. She reported the presence of artisanal pots. She initially denied the use of any imported medicines, food, or jewelry items but later admitted eating imported Mexican foods such as taquis, totis, mole, bread, pumpkin seeds, and tamarindo, as well as use of lipstick from the 99 cent store. During her first pregnancy she reported eating “tierra” and “tequesquite” but denied eating these with the most recent one.

She was taking prenatal vitamins, iron, vitamin D, calcium supplements, and famotidine. She reported drinking two cups of milk, and eating cheese, yogurt daily and chicken several times a week. She denied pica behavior and non-nutritive hand/object to mouth activity.

She lived with husband and children ages 5 and 3, neither of whom had a BLL over 4 µg/dL when tested during her most recent pregnancy. She is unemployed and her husband works at a car wash.

Discussion

Lead exposure during pregnancy may result in harm to both the pregnant woman and the fetus. The Centers for Disease Control and Prevention (CDC) estimates that 0.7% of women between the ages of 15 and 49 years had a BLL of over 5 µg/dL in the period 2011–2016, the pediatric cutoff for intervention. ¹ The characteristics of lead poisoning in pregnancy are different than in its occurrence in childhood. The women are more likely to be foreign born and the source of lead is rarely peeling paint. ² The consequences for fetal development range from subtle small decreases in anthropomorphic measures at birth to intrauterine death. Pregnancy is not protective against the spectrum of adult lead poisoning.

The management of lead poisoning during pregnancy follows guidelines similar to those in use for non-pregnant individuals: (1) eliminate sources of exposure; (2) end non-nutritive oral behavior; (3) achieve appropriate nutrition requirements, especially for calcium, iron, vitamin D, and vitamin C, and; (4) drug treatment to enhance lead excretion, i.e. chelation therapy. ³ In children, a BLL of 45 µg/dL or more is an indication for chelation.^3,4 While for adults there is no agreed threshold for chelation, the CDC recommends a BLL of 45 μg/dL as the level at which to consider chelation during pregnancy. However, in animal studies, all the currently available drugs are potential teratogens. We therefore delay chelation to the middle of pregnancy whenever possible unless the mother’s life is at immediate risk.

The gold standard drug used for chelation in non-pregnant people is succimer. Experience with chelation during pregnancy, however, is very limited and is almost entirely with CaNa₂EDTA. This parenterally administered drug has been effective at reducing both maternal and fetal BLLs without apparent toxicity. The price of CaNa₂EDTA has markedly increased so it is now much less readily available, hence the delay in obtaining it in this case. Two case reports where succimer was used failed to show efficacy, possibly because treatment appeared to be outpatient based without control of ongoing lead exposure.^5,6 The use of succimer in this case was well tolerated. There were no significant changes in her biochemistry or hematological parameters in relation to the succimer use.

The case described here demonstrates the unusual occurrence of a second episode of lead poisoning during pregnancy. It remains unclear whether this was the result of a new ingestion or from remaining bone lead stores. Given the sustained decline in BLL after the first episode it is possible she discovered a new source during the latter pregnancy. However, once lead accumulates in bone it may remain for many years. This case is further complicated by her vitamin D deficiency and hyperparathyroidism. Regardless of whether her hyperparathyroidism was primary or secondary to her vitamin D deficiency, PTH-stimulated osteoclastic bone resorption would result in mineral release into blood, including lead if present. Thus the lead poisoning observed in this second episode could be ascribed to bone release and/or new lead ingestion.

Finally, newborn cord BLL and maternal BLL at the time of labor and delivery are highly correlated in many studies (Figures 1 and 2). That does not mean they are identical. In her two infants, the first had a BLL within the measurement error of her mother’s. However, the second baby’s BLL was considerably higher and he required chelation therapy. For this reason, newborn BLLs should always be obtained in those born to mothers with lead poisoning.

Figure 1.

Maternal blood lead levels (BLLs) over time reflecting two episodes of severe lead poisoning occurring during two pregnancies. The steep decline in BLLs reflects the end of courses of chelation therapy. The subsequent rise from trough levels most likely represents release of lead from bone stores into blood.

Figure 2.

Blood lead levels in the newborn. First level is from cord blood and subsequent are from venous samples. The steep initial fall in BLLs occurred immediately after a course of succimer chelation. Subsequent stability in the levels indicates substantial bone lead stores as a result of his in-utero exposure. This figure shows results of the neonate from the most recent pregnancy i.e., the second case of fetal plumbism for this woman. plumbism for this woman.