Pregabalin Abuse During Pregnancy and Global Developmental Delay in Infants

Pregabalin is a medication licensed for the treatment of epilepsy and anxiety disorders. In addition, Pregabalin is increasingly recognised as a drug of abuse. Teratogenic effects have been demonstrated in animal models, however, there is a dearth of research relating to potential teratogenic effects in humans. This case highlights the potential role of intrauterine exposure to Pregabalin in contributing to Global Developmental Delay in two children.

Pharmacokinetics of Baclofen in a Full-Term Newborn after Intrauterine Exposure: A Case Report

Intrauterine exposure to baclofen can lead to syndrome of withdrawal during the first days of the newborn. We report the case of a full-term baby exposed to baclofen during pregnancy. The mother was treated with baclofen 10 mg 4 times daily. Blood samples were collected from the mother before entering labor and from the baby at H0, H11, H31, and H102 after birth to measure baclofen concentrations and monitor its elimination. Baclofen maternal and neonate pharmacokinetics (PK) and placental transfer were assessed using a physiologically based PK model. Baclofen PK in the neonate after birth followed a monoexponential elimination with a half-life of 10 h, 3-fold longer than that in adults. The newborn was monitored for 11 days without experiencing any symptoms of withdrawal. Reducing baclofen dosing regimen of the mother to the lowest and therefore reducing fetal exposure to baclofen is essential. This case reports for the first time the baclofen pharmacokinetic profile in a newborn.

Transplacental Transfer of Primaquine and Neurobehavioral Development of Prenatally Exposed Rats

Primaquine (PQ) not only eliminates P. falciparum gametocytes but also kills liver dormant forms of P. vivax and P. ovale. Owing to these unique therapeutic properties, it is an essential drug. Although PQ has been used for over 70 years, its toxicological database has gaps such as the absence of studies on its reproductive and developmental toxicity and kinetics in pregnancy. This study investigated the transplacental transfer of PQ and the effects of intrauterine exposure on the postnatal growth, survival, and neurobehavioral development of the offspring. PQ kinetics and transplacental transfer were investigated in rats treated orally (40 mg.kg·bw−1) on gestation day (GD) 21. PQ was analyzed by high-performance liquid chromatography with diode array ultraviolet detection. To evaluate effects of intrauterine exposure on postnatal development, dams were treated orally with PQ (20 mg.kg·bw−1·d−1) or water (controls) on GD 0–21. Postnatal survival, body weight gain, somatic maturation, and reflex acquisition were evaluated. The open field test (OF) was conducted on PND 25. PQ concentration in the fetal plasma was nearly half that in maternal plasma. Except for increase in pregnancy loss, no effects of PQ were noted at term pregnancy and first days of life. Prenatal PQ did not affect postnatal weight gain nor did it impair somatic and neurologic development of the offspring. Pups born to PQ-treated dams showed reduced exploration and enhanced emotionality in the OF. PQ given in pregnancy, at doses greater than those recommended for malaria therapy, may affect pup postnatal survival and emotional behavior.

Intrauterine Exposure to Vitamin B12 and Folate Imbalance and Brain Structure in Young Adults of the Pune Maternal Nutrition Study (PMNS) Birth Cohort

Objectives Intrauterine nutritional exposures to vitamin B12 and folate are known to influence neurodevelopment. We tested the hypothesis that intrauterine exposure to high folate in presence of low vitamin B12 is associated with poor neurodevelopmental outcomes in young adult offspring. Methods PMNS is a preconceptional birth cohort in its 24th year of follow up. We examined Intelligence Quotient (IQ) and obtained brain structural MPRAGE T1 sequence on a 3T MRI Scanner [participants selected based on exposure to maternal B12 at 18 wk pregnancy <103 PM(Low maternal B12 group n = 97) and >175 pM (high maternal B12 group, n = 93)]. Brain morphometric measurements (cortical volumes, thickness and subcortical volumes) were performed on Freesurfer software. Results The mean age of participants was 22.3 ± 0.5 years (n = 190, 96 boys). High maternal B12 group showed greater cortical thickness in temporal regions (P < 0.001) and cortical thinning in frontal regions (P < 0.01). Higher maternal folate (median Red Cell Folate at 28 wk pregnancy 420 ng/ml) was associated with greater frontal cortical volumes in the high maternal B12 group but cortical thinning in multiple temporal and parietal cortical areas in the low B12 group(P < 0.05). There was a significant interaction between maternal B12 and folate status in relation to subcortical volumes. Exposure to higher maternal folate was associated with greater subcortical volume in high B12 group but lower volumes in low B12 group (P = 0.02, adjusted for age, education, gender and total intracranial volume). Higher IQ score was associated with larger subcortical brain volume (r = 0.34, P < 0.001) in the offspring. Conclusions Intrauterine exposure to higher maternal folate in the presence of low vitamin B12 was associated with poorer cortical development in young adult offspring. Higher maternal folate with adequate B12 benefits subcortical brain development which reflects in higher IQ score. Optimizing maternal vitamin B12 and folate concentrations during pregnancy would benefit neurocognitive development in the offspring. Funding Sources DBT Wellcome India Alliance Clinical and Public Health Intermediate Fellowship.