ABSTRACT
BACKGROUND: Maternal exposure to pesticides during pregnancy may cause oxidative hemolysis leading to neonatal hyperbilirubinemia. This investigation examined for associations between maternal use of pesticides or repellents during pregnancy and neonatal hyperbilirubinemia requiring phototherapy. METHODS: We used the dataset from the Japan Environment and Children's Study, a large national birth cohort study registered from January 31, 2011 to March 31, 2014. The fixed data of 61,751 live births were used to evaluate the presence of neonatal hyperbilirubinemia and potential confounding factors. We employed multiple logistic regression analysis to identify correlations between the frequency of maternal pesticide or repellent use during pregnancy and clinically relevant neonatal hyperbilirubinemia. RESULTS: After controlling for confounding factors, there were significant associations between neonatal hyperbilirubinemia necessitating phototherapy and the frequent use of indoor insecticide spray (OR 1.21, 95% CI 1.05-1.38). For spray- or lotion-type insect repellents, an opposite relationship was observed (more than a few times a week: OR 0.70, 95% CI 0.61-0.81, up to a few times a month: OR 0.84, 95% CI 0.78-0.91). CONCLUSION: The frequent use of indoor insecticide spray during pregnancy showed an increased risk of neonatal hyperbilirubinemia requiring phototherapy, which was absent for spray- or lotion-type insect repellents. IMPACT: The frequent use of indoor insecticide spray during pregnancy showed an increased risk of neonatal hyperbilirubinemia requiring phototherapy, which was absent for spray- or lotion-type insect repellents. This is the first study examining the effects of maternal exposure to pesticides or repellents on clinically relevant neonatal hyperbilirubinemia using a dataset from a nationwide birth cohort study. This large-scale Japanese cohort study revealed that the frequent use of indoor insecticide spray during pregnancy may increase the risk of neonatal hyperbilirubinemia requiring treatment.
Subject(s)
Hyperbilirubinemia, Neonatal/chemically induced , Hyperbilirubinemia, Neonatal/therapy , Pesticides/toxicity , Adult , Child , Female , Humans , Infant, Newborn , Japan , Male , Maternal Exposure , PregnancyABSTRACT
INTRODUCTION: Mitochondrial dysfunction results in a wide range of organ disorders through diverse genetic abnormalities. We herein present the detailed clinical course of an infant admitted for extensive, rapidly progressing white matter lesions and hypertrophic cardiomyopathy due to a BOLA3 gene mutation. CASE: A 6-month-old girl with no remarkable family or past medical history until 1â¯month prior presented with developmental regression and feeding impairment. Ultrasound cardiography and brain magnetic resonance imaging (MRI) respectively disclosed the presence of hypertrophic cardiomyopathy and symmetrical deep white matter lesions. She was transferred to our hospital at age 6â¯months. High lactate levels in her cerebrospinal fluid suggested mitochondrial dysfunction. Despite vitamin supplementation therapy followed by a ketogenic diet, the patient began exhibiting clusters of myoclonic seizures and respiratory failure. Brain and spinal cord MRI revealed rapid progression of the white matter lesions. She died at 10â¯months of age. Fibroblasts obtained pre-mortem displayed low mitochondrial respiratory chain complex I and II activity. A homozygous H96R (c. 287 Aâ¯>â¯G) mutation was identified in the BOLA3 gene. DISCUSSION: No reported case of a homozygous BOLA3 gene mutation has survived past 1â¯year of life. BOLA3 appears to play a critical role in the electron transport system and production of iron-sulfur clusters that are related to lipid metabolism and enzyme biosynthesis.
Subject(s)
Brain Diseases/genetics , Cardiomyopathy, Hypertrophic/genetics , Mutation , Proteins/genetics , Spinal Cord Diseases/genetics , Brain Diseases/diagnostic imaging , Brain Diseases/pathology , Brain Diseases/physiopathology , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/pathology , Cardiomyopathy, Hypertrophic/physiopathology , Fatal Outcome , Female , Humans , Infant , Mitochondrial Proteins , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/pathology , Spinal Cord Diseases/physiopathologyABSTRACT
Phospholipase D (PLD) catalyzes transphosphatidylation, causing inter-conversion of the polar head group of phospholipids and phospholipid hydrolysis. Previously, we cloned PLD103, a PLD with high transphosphatidylation activity, from Streptomyces racemochromogenes strain 10-3. Here, we report the construction of an expression system for the PLD103 gene using Streptomyces lividans as the host bacterium to achieve large-scale production. The phosphatidylcholine (PC) hydrolysis activity of S. lividans transformed with the expression plasmid containing the PLD103 gene was approximately 90-fold higher than that of the original strain. The recombinant PLD103 (rPLD103) found in the supernatant of the transformant culture medium was close to homogeneous. The rPLD103 was indistinguishable from the native enzyme in molecular mass and enzymatic properties. Additionally, rPLD103 had high transphosphatidylation activity on PC as a substrate in a simple aqueous one-phase reaction system and was able to modify the phospholipid content of soybean lecithin. Consequently, the expression system produces a stable supply of PLD, which can then be used in the production of phosphatidyl derivatives from lecithin.