Increased Risk of ADHD in Children Exposed to Maternal Sickle Cell Disease

Martha Brucato, MD

Children exposed to maternal sickle cell disease were at an increased risk of attention deficit hyperactivity disorder and obesity, according to a new study from Maryland.

Over 95% of children with SCD have been shown to survive well into adulthood in resource-rich settings. As such, concerns have been raised regarding he implications of the disease on reproductive outcomes.

In previous research, pregnancy complications in women with SCD, including maternal anemia, inflammatory and abnormal immune activation, preeclampsia, intrauterine growth restriction, low birth weight and more, had been linked to developmental disorders in children.

However, developmental outcomes of children exposed to maternal SCD remained poorly defined.

As such, and investigative team led by Martha Brucato, MD, of Johns Hopkins University School of Medicine, utilized data from The Boston Birth Cohort (BBC) to evaluate developmental outcomes of children born to mothers with SCD compared to matched controls.

The BBC was an extensive, prospective birth cohort that was developed at the Boston Medical Center in 1998. The cohort collected data on pre-term and full-term mother-baby dyads.

For this investigation, dyads with multiple gestations, infants with chromosomal abnormalities or major birth defects, infants conceived through in vitro fertilization, and preterm delivery due to traumatic injury were excluded.

The team identified all women in the cohort with ICD-9-CM codes for SCD that were featured in the cohort from October 1, 2003, and September 31, 2015.

Eligible dyads were matched with unaffected controls in a 1:3 ratio through a propensity score analysis, which matched cases and controls based on probability of exposure to maternal SCD, conditional on race, marital status, education, and child’s year of birth.

From there, investigators calculated the log odds of maternal SCD status as a function of race, marital status, education, and child’s year of birth and obtained fitted probabilities for all subjects.

Delayed milestones, speech and language delays, ADHD, unspecified development delay, and physical development disorders were among the neurodevelopment disorders (NDD) identified with the utilization of ICD-9-CM codes.

Among the 5972 mothers featured in the cohort, data was available for 2992 children. A total of 48 women featured among the mother-child dyads had at least 1 ICD-9-CM code for SCD.

After various exclusions, a total of 40 dyad cases and 120 controls were featured in the final analysis.

Self-identification revealed that 42.5% of patients identified as Black while 37.5% identified as Haitian, while the mean gestational age at birth among children born to women with SCD was 38.77 weeks.

Investigators observed that NDD occurred in 38% of children exposed to maternal SCD, which included delayed milestones (15%), other developmental speech or language delay (18%), ADHD (15%), and unspecified delay in development (13%).

Notably, ADHD risk increased in children born to mothers with SCD (P=0.02), as did physical developments (58%) included increased risk of obesity (P=0.03) and decreased risk of abnormal weight loss (P=0.03).

Brucato and colleagues noted that these findings could prove relevant in future research, as well as for hematologists and pediatricians who care for women and children affected by SCD.

“These studies are needed to define the physical and neurodevelopmental risks for this vulnerable and understudied population of women and children,” the team wrote.

The report, "Developmental disorders in children born to women with sickle cell disease: A report from the Boston Birth Cohort," was published online in eJHaem.