Newborn with In Utero Lead Toxicity

A female infant is born at 40 weeks 2 days gestational age to a 29-year-old gravida 7, para 1 mother via vaginal delivery with Apgar scores of 9 and 9 at 1 and 5 minutes. Routine steps are performed at birth, and the infant is admitted to the newborn nursery. Findings from the infant's physical examination, including a detailed neurologic examination, are normal.The antenatal history is significant for threatened abortion at 14 weeks' gestational age and pica, which began during the first trimester, resulting in ingestion of paint chips at home. Maternal blood lead levels (BLLs) remained elevated throughout pregnancy, with the highest level during the third trimester (range, 16–42 µg/dL [0.77–2.03 µmol/L]).Mother had a similar habit during adolescence, but she claims to have none during her previous pregnancies and denies any neurodevelopmental or behavioral disorders in her only living child. She had 5 spontaneous abortions before her successful pregnancies. The case was further escalated to the Department of Health (DOH) by her obstetrician during the first trimester antenatal visits, and necessary measures were taken by the DOH, including a thorough inspection and repainting of the house.At birth, the infant's screening test is remarkable for a capillary lead level of 32 µg/dL (1.54 µmol/L) (newborn reference values, <3.5 µg/dL [<0.17 µmol/L]). Additional evaluations for the infant, including complete blood cell count and iron studies, are obtained, and the results are within normal limits for age. Screening head ultrasonography is performed and is reported to have normal findings. A lead poisoning specialist is consulted for recommendations on further management of the patient. The infant is advised to have close monitoring with serial follow-up for repeated BLLs, and no chelation therapy is recommended at the time. Also, no further neuroimaging studies or a skeletal survey is recommended. However, following the Centers for Disease Control and Prevention (CDC) guidelines to defer human milk with maternal BLLs of 40 μg/dL or greater (≥1.93 µmol/L), the mother is advised not to breastfeed the infant at the time. (1)After an uneventful nursery stay, the infant is discharged on the second day after birth. A routine health supervision appointment with the primary care pediatrician, a lead clinic appointment, and an early intervention program referral were made before discharge. As per local DOH protocol, a venous lead level is collected on the infant in the primary care clinic after 1 week, which is remarkable for a BLL of 28 µg/dL (1.35 µmol/L), followed by a repeated level of 30 µg/dL (1.45 µmol/L) collected in the lead clinic after 2 weeks. Thereafter, serial testing for follow-up BLLs in the infant at 2, 4, 8, and 11 months are 19 µg/dL (0.92 µmol/L), 21 µg/dL (1.01 µmol/L), 14 µg/dL (0.68 µmol/L), and 8 µg/dL (0.39 µmol/L), respectively.Currently, the infant is 12 months old and continues to follow up in the lead clinic and has regular health supervision visits in the primary care clinic; she requires close neurodevelopmental monitoring, with no active concerns to date. In addition, she is being followed by an early intervention program. She is up to date on immunizations, growing appropriately for age, achieving milestones on time, and shows no developmental delays. Her most recent lead level is 8 μg/dL (0.39 µmol/L).Lead poisoning is a type of poisoning caused by the highly toxic metal lead in the body. It is a cumulative toxicant that affects multiple body systems and is particularly harmful to infants and growing children. Due to its structural similarity to calcium, lead competes with calcium for absorption in the gastrointestinal tract and is primarily stored in bones and teeth. (2) Lead stored in bones has a longer half-life (20–30 years) and can be mobilized into blood and soft tissues during periods of heightened bone turnover, such as pregnancy and lactation. Elevated lead levels in pregnancy have been associated with gestational hypertension, spontaneous abortion, low birthweight, and preterm labor. (1) Lead readily crosses the placenta via passive diffusion, thus the fetal lead level is the direct reflection of the concentration of lead in the maternal blood. Lead levels in human milk also increase with increases in maternal lead levels (Fig). (1)(3) In this case, the child was never breastfed by the mother during the first year after birth.Children with lead toxicity may be completely asymptomatic. Acute lead toxicity should be suspected in children presenting with gastrointestinal symptoms such as constipation or obstipation, vomiting, or anorexia and neurologic changes such as lethargy, irritability, or hyperactivity. Physical examination findings may include evidence of increased intracranial pressure or pallor resulting from severe anemia. (4)Lead is known to interfere with synaptogenesis, thus negatively impacting fetal brain cells in the developing brain. It substitutes for calcium and zinc as a second messenger, which in turn interferes with stimulated neurotransmitter release at synapse, disrupting cell differentiation, myelination, and organization of synaptic connections. (2)(5) The permeable nature of the fetal blood-brain barrier makes the fetal brain cells more sensitive to lead. Because there is less bone tissue in the fetus for sequestering lead, the developing central nervous system becomes considerably vulnerable to lead toxicity. (1)(6)Children exposed to lead in utero have been widely demonstrated to have poor cognition, learning difficulties, behavioral issues, and attention problems even at levels below the upper limit of the reference value of 5 µg/dL (0.24 µmol/L) set by the CDC. (7) Multiple studies have shown that in utero exposure to even low levels of lead can affect infant and child growth and neurodevelopment likely due to altered neuronal connectivity and atypical patterns of brain development. (7)(8) Results of a cohort study by Fruh et al(7) demonstrated that BLLs were related to impaired executive function and behavioral difficulties. Similarly, Markowitz(9) reported an inverse relationship between BLL and IQ, with an estimated 0.5-point loss for every 1-µg/dL (0.05-µmol/L) increase in BLL, as well as a direct relationship between lead levels of 20 μg/dL and greater (≥0.97 µmol/L) and attention deficits and disruptive and aggressive behaviors in children. Lead poisoning can also present as encephalopathy, seizure, and death with significantly elevated levels higher than 100 μg/dL (>4.83 µmol/L). (9) To mitigate these effects, chelation therapy should always be considered when the BLL reaches 45 μg/dL (2.17 µmol/L). At levels lower than 45 µg/dL (<2.17 µmol/L), chelation therapy has not been shown to decrease the negative effects of lead. (10)Accumulation of lead in other organs may also have subclinical effects. Lead inhibits erythropoiesis by reducing erythropoietin production and decreasing red blood cell survival. Gouty nephropathy with decreased glomerular filtration may occur, resulting in renal insufficiency and Fanconi syndrome. Spermatogenesis may likewise become impaired. Other effects include hearing loss, hypertension, and stunted growth. (9)Routine blood lead testing of pregnant women is not recommended by the American College of Obstetricians and Gynecologists. Individuals are evaluated based on certain risk factors, including recent emigration from areas of high ambient lead contamination; living or working near a point source of lead; using lead-glazed ceramic pottery; eating nonfood substances; renovating or remodeling older homes without lead protection; using alternative substances, herbs, or therapies; using imported ceramics; engaging in high-risk activities, such as pottery making; having a history of previous lead exposure; or living with someone with an elevated lead level. Blood lead testing is then performed if a single risk factor is identified. (11)In a child with an elevated BLL, screening for iron deficiency anemia, including a complete blood cell count, ferritin level, and C-reactive protein level, should be performed. Liver and renal function testing is performed for children requiring chelation therapy. (12) The inhibition of heme synthesis leads to the accumulation of excess porphyrins. The level of erythrocyte protoporphyrin, which is assayed as zinc protoporphyrin, is elevated when lead levels are greater than 20 μg/dL (>0.97 µmol/L). In children with higher BLLs, serial measurement of erythrocyte protoporphyrin levels is a useful indicator of the effects of lead as well as the efficacy of treatment. (9) A plain abdominal radiograph to assess for radio-opaque lead flecks is reserved for symptomatic children with a history of pica or ingestion of lead-containing products and in children with an unexpected acute rise in BLL. (12)Despite improvements in environmental policies and significant reduction in US average BLLs, lead exposure remains a concern for pregnant and lactating women. Elevated maternal BLLs are not uncommon with lead exposure during pregnancy. This is a unique case of a newborn demonstrating significantly high BLLs at birth after in utero exposure.Primary prevention is still needed despite our general education about lead exposure.Continuous efforts must be made to bring awareness and eliminate prenatal exposure to lead to prevent detrimental outcomes in vulnerable infants.More importantly, due to the potential neurodevelopmental impact of lead, prompt identification and close monitoring of infants with elevated lead levels should be emphasized.