Congenital lead toxicity is rare. Lead freely crosses the placenta, therefore, placing the developing fetus at a higher risk for lead toxicity. This can lead to adverse consequences, such as spontaneous abortion, low birth weight, low IQ, and neurodevelopmental impairment. We present a rare case of siblings born to a mother with pica behaviors. Her venous lead level was 42 μg/dL at the time of disclosure. The repeat venous level at delivery 2 weeks later was 61 μg/dL. The infant’s venous level shortly after birth was 89 μg/dL. The neonate was transferred to the NICU, where he received 9 doses of intramuscular dimercaprol and 5 days of intravenous Ca2Na2EDTA. Seventy-two hours after completing chelation, the blood lead level rebounded to 46 μg/dL. A 19-day course of dimercaptosuccinic acid was then initiated. As of 12 months of age, he has not required additional chelation. Shortly after, the mother conceived another child, who was born prematurely at 29 weeks. Twelve days before delivery, the mother’s lead level was 30 ug/dL. The infant’s lead level was 32 ug/dL at the time of delivery. The infant’s lead trended down without requiring chelation. Both children have since demonstrated developmental delays and have needed early intervention services.

Lead is a neurotoxin that has irreversible effects on the developing nervous system. Even low levels of lead can have long-term effects, including, but not limited to, decreased IQ, behavior problems, and developmental delay.1 More importantly, prenatal lead exposure can lead to spontaneous abortion, prematurity, and intrauterine growth restriction.2 The routine universal blood lead screening of all women during pregnancy is not recommended by the Centers for Disease Control and Prevention (CDC) or the American College of Obstetricians and Gynecologists, but a risk assessment is advisable.3,4 

Congenital lead poisoning appears to be rare; however, it remains inadequately documented, highlighting a gap in available data on this critical issue. Approximately 0.5% to 1% of women of childbearing age have high blood lead levels.4 In 2016, it was estimated that ∽590 000 American children between the ages of 1 and 5 had elevated blood lead levels of 3.5 μg/dL or more.5 These figures underscore the need for ongoing efforts to prevent and address lead exposure in children. However, there are no national or local chelation protocols for neonates. Chelation is recommended in children with lead levels >45 ug/dL or children who are symptomatic.2 Levels >70 ug/dL increase the risk for encephalopathy and require special considerations during chelation.2 In this article, we present 2 cases of congenital lead poisoning in siblings, which introduces complex clinical questions and highlights the need for better screening tools for at-risk populations.

At 37 weeks gestation, a mother disclosed to her obstetrician that she was having increasing pica behaviors. She described a long history of pica behaviors and at that time was eating 4 to 5 cups of dirt per day. She also reported that she had a long history of lead poisoning, which required chelation therapy when she was a young child. Her lead level at 37 weeks was 42 μg/dL. Other pertinent history included opiate abuse with a successful transition to Subutex. At 39 weeks, her lead level was 61 μg/dL on admission for induction. The neonate’s lead level at 10 hours of life was 89 μg/dL, and the zinc protoporphyrin (ZPP) level was 201 μg/dL (reference range <100 μg/dL). He was transferred from an outside hospital to a level 4 NICU for ongoing care. On admission, central umbilical lines were placed for treatment. He received intramuscular dimercaprol and calcium disodium EDTA for his initial chelation regimen. The dimercaprol was dosed at 100 mg/m2/dose every 8 hours, for a total of 9 doses. Dosing was altered to every 8 hours, as opposed to the standard 4-hour interval, to decrease the risk of renal impairment. Calcium disodium EDTA was dosed at 30 mg/kg/d for 23 hours per day for 5 days, which was started 6 hours after the first dose of dimercaprol.

The neonate was closely monitored for signs and symptoms of nephrotoxicity and was on a cardiac monitor during the infusion because sodium calcium EDTA is known to be arrhythmogenic. He received maintenance intravenous fluids throughout chelation and received 2 normal saline boluses as follows: once when his urine output decreased to 0.6 ml/kg/h and subsequently for an episode of microscopic hematuria. His renal function remained normal throughout the chelation. He was initially slow to establish feeding and was irritable. He was being monitored closely for opiate withdrawal. It was difficult to assess whether the irritability and feeding difficulties were due to opiate withdrawal or encephalopathy secondary to lead poisoning. Scheduled morphine was initiated for neonatal abstinence syndrome, which improved his feeding and irritability. Long bone films were obtained as part of his initial workup, showing no signs of lead deposition. An initial complete blood count revealed the hemoglobin and hematocrit were 14.9 g/dL and 43%, respectively.

Initially, he responded well to this treatment, and his lead level decreased to 29 μg/dL after completing this chelation regimen. The neonate’s lead level rebounded to 46 μg/dL only 72 hours after completing his initial regimen. Chelation therapy was reinitiated with oral dimercaptosuccinic acid. The standard dosing is 10 mg/kg/dose rounded to the nearest hundred milligrams. Because of his young age and weight, it was rounded down to 50 mg of dimercaptosuccinic acid by mouth every 8 hours for 5 days and then every 12 hours for 14 days. His liver function and absolute neutrophil count were monitored during his course because dimercaptosuccinic acid is known to cause an increase in transaminases and neutropenia. After completion of chelation, his lead level decreased to 33 μg/dL, and his ZPP was 239 μg/dL (Fig 1). His morphine was weaned gradually and stopped before discharge.

FIGURE 1

Timeline of chelation therapy and response to treatment.

FIGURE 1

Timeline of chelation therapy and response to treatment.

Close modal

There were significant social concerns due to maternal substance abuse and a history of pica during pregnancy. His case was referred to the Department of Children and Families for undisclosed reasons unrelated to lead exposure. He was discharged into foster care. Referrals to early intervention services, audiology, neurodevelopment, and a lead treatment center were placed. The infant has not required additional chelation. At 12 months, his lead level was 15 μg/dL, and his ZPP level was 45 μg/dL. He continues to receive early intervention services for hypertonia and gross motor delay and follows closely with the lead treatment center.

The same mother delivered a preterm infant at 29 weeks’ gestation, 19 months after the first infant. In the interim, the mother reported that her pica behaviors had improved, but her lead level was 30 ug/dL 12 days before delivery. The second infant was delivered via cesarean delivery because of concern for placental abruption. At delivery, urine drug screen results for both the mother and the infant were positive for cocaine and suboxone. After initial resuscitation and stabilization, the infant was placed on continuous positive airway pressure. Subsequently, the infant started having seizure-like activity with rhythmic tonic-clonic movements of the right upper extremity, accompanied by desaturations. The infant was then intubated at that time. Serial cranial ultrasounds were normal. An EEG was performed, and no evidence of seizure-like activity was found. The initial lead level for the infant was 32 ug/dL, with a ZPP level of 169 μg/dL. The lead levels decreased to 29 ug/dL and 22 ug/dL at 24 hours and 1 week of life, respectively. At 3 weeks of life, the lead level had decreased to 15 ug/dL. The long bone films of the infant did not show any evidence of lead deposition.

Despite the neonate’s lead level being less than the standard threshold for chelation, chelation was considered when the neonate had seizure-like activity because symptomatic lead poisoning is an indication for chelation. A double-exchange transfusion was also considered, which has been performed for neonates with high lead levels in the past.6,7 In these reported cases, the lead levels were much higher, and the risks versus the benefits of a double-exchange transfusion were not justified for our patient. There is currently limited guidance for the treatment of lead poisoning in preterm neonates. It was decided to monitor without intervention after reviewing the risks and benefits.

The neonate fared well after a short stay in the NICU. Because of continued social concerns, this child was placed in the same foster home as his sibling. There has been follow-up with early intervention services, a neurodevelopmental clinic, and the lead treatment center.

We present a rare case series of siblings with congenital lead toxicity, one of whom required 2 courses of chelation therapy. When a child is exposed to lead, it is absorbed into their bones, mineralizing tissues, teeth, and soft tissues. It can take months to years to leave the body altogether.8,9 Chelation decreases the blood lead level. Thus, serum lead levels often rebound after chelation because of the redistribution of the lead within the body.10,11 A rebounded lead level can reach up to 75% of the pretreatment level.12 There are limited data and guidelines specific to the neonatal population to guide clinicians.8,11 Over the latter half of the 21st century, blood lead levels (BLLs) have been steadily declining; despite this decline, the NHANES revealed that more than half a million preschool children in the United States had BLLs ≥5 μg/dL, and 1% of women of childbearing age have BLLs ≥5 μg/dL.2 The risk is more significant in utero and for neonates because of their immature blood–brain barrier, potentially leading to greater absorption of lead.13 The long-term adverse effects of lead on children have been extensively documented in the literature, including intellectual impairment and developmental disorders.14–16 Recently, studies have revealed that fetal exposure to lead alters neural connectivity in areas that affect higher-order cognitive functions.17 

Lead levels >70 μg/dL increase the risk of encephalopathy, coma, seizure, and death in infants and children.9 Current chelation protocols and guidelines recommend starting treatment after discussion with experts because of the complexity of chelation at these high levels.8 Moreover, the chelation agents also carry their own risks. The CDC recommends starting chelation in children with a confirmed BLL of ≥45 µg/dL or any symptomatic child.8 Medications for chelation include dimercaptosuccinic acid, sodium calcium EDTA, dimercaprol, and D-penicillamine.8,18,19 In addition, single- and double-volume exchange transfusions have also been used to help reduce lead levels rapidly.6,7 The CDC also recommends chelation with dual agents for levels >70 due to the risk of encephalopathy.8 Due to a lack of chelation protocols for neonates, a combination of sodium calcium EDTA and low-dose dimercaprol was used to limit toxic effects on the neonatal kidney in this patient.

It is estimated that at least 500 000 women are being exposed to lead, which could pose harm to fetuses, neonates, and breastfed infants.3 This case highlights 2 critical areas that need improvement. First, it highlights the importance of appropriately managing pregnant women with high blood lead levels.3,20 In this case, the mother openly disclosed her pica behaviors late in pregnancy. Once the initial lead level resulted at 42 ug/dL, there was no intervention to aid the mother in decreasing her exposure and no follow-up testing until she was admitted for induction. We recommend the continued education of providers caring for pregnant women on the risks of lead poisoning and the importance of timely management and targeted screening. Second, there are no guidelines or protocols in the literature for chelating neonates. This neonate’s chelation protocol was selected on the basis of available protocols for older children. Given the ethical contraindications to performing controlled trials in this subset of patients, we recommend the development of protocols for the chelation of neonates.

Dr Velagala assisted in conceptualizing and designing the study and drafting the initial manuscript; Dr Chhikara cared for one of the patients and drafted a portion of the initial manuscript; Dr Haile directed patient care and assisted in conceptualizing and designing the study; and all authors critically reviewed and revised the manuscript for important intellectual content, approved the final manuscript as submitted, and agreed to be accountable for all aspects of the work.

BLL

blood lead level

CDC

Centers for Disease Control and Prevention

ZPP

zinc protoporphyrin

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Competing Interests

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose.