Growth Differentiation Factor 15 (GDF15) is a divergent member of transforming growth factor-beta (TGF-β) superfamily and is ubiquitously expressed, under normal physiological conditions. GDF15 expression increases during many pathological states and serves a marker of cellular stress. GDF15 has multiple and even paradoxical roles within a pathological condition, as its effects can be dose- and time-dependent and vary based on the targeted tissues and downstream pathways. GDF15 has emerged as one of the most recognized proteins as part of the senescence associated secretory phenotype. Cellular senescence plays a major role in many lung diseases across the life-span from bronchopulmonary dysplasia in the premature neonate to COPD and idiopathic pulmonary fibrosis in aged adults. GDF15 levels have been reported to be as a useful biomarker in chronic obstructive pulmonary disease, lung fibrosis and pulmonary arterial hypertension and predict disease severity, decline in lung function and mortality. Glial-cell-line-derived neurotrophic factor family receptor alpha-like (GFRAL) in the brain stem has been identified as the only validated GDF15 receptor and mediates GDF15-mediated anorexia and wasting. The mechanisms and pathways by which GDF15 exerts its pulmonary effects are being elucidated. GDF15 may also have an impact on the lung based on the changes in circulating levels or through the central action of GDF15 activating peripheral metabolic changes. This review focuses on the role of GDF15 in different lung diseases across the lifespan and its role in cellular senescence.

Cairo, Egypt (Correspondence to W. Al-Darzi: waleed.aldarzi@gmail.com).Received: 03/01/13; accepted: 23/06/13 ABSTRACT Egypt has a high incidence of neural tube defects. Folic acid supplementation in the periconceptional period is known to lower the risk of such defects. This cross-sectional study aimed to measure the level of knowledge about periconceptional folic acid use among pregnant women attending for antenatal care at Ain Shams University Hospital, Cairo, Egypt in 2012. Questionnaires were filled through personal interviews with 660 pregnant women. Of the respondents, 62.4% had heard of folic acid and 39.2% knew about the role of folic acid supplementation in prevention of congenital anomalies. Knowledge about using folic acid before and in the first trimester of pregnancy was highest among university-educated women and those working in professional occupations. Only 18.8% of women reported taking folic acid, and 8.8% had used it before conception. Awareness campaigns are suggested to improve knowledge about folic acid among women in the childbearing period in Egypt. ‫مرص‬ ‫القاهرة،‬ ‫شمس،‬ ‫عني‬ ‫جامعة‬ ‫مستشفى‬ ‫يف‬ ‫احلوامل‬ ‫النساء‬ ‫لدى‬ ‫باحلمل‬ ‫املحيطة‬ ‫الفرتة‬ ‫يف‬ ‫الفوليك‬ ‫محض‬ ‫باستخدام‬ ‫املعرفة‬

BACKGROUND: Mercury (Hg) and lead (Pb) exposure during childhood is associated with irreversible neurodevelopmental effects. Fetal exposure to Hg and Pb from intrauterine blood transfusion (IUBT) has not been reported. METHODS: Fetal exposure was estimated based on transfusion volume and metal concentration in donor packed red blood cell (PRBCs). As biomarkers to quantify prenatal exposure are unknown, Hg and Pb in donor PRBCs were compared to estimated intravenous (IV) RfDs based on gastrointestinal absorption. RESULTS: Three pregnant women received 8 single-donor IUBTs with volumes ranging from 19 to 120 mL/kg. Hg and Pb were present in all donor PRBC units. In all, 1/8 IUBT resulted in Hg dose five times higher than the estimated IV RfD. Median Pb dose in one fetus who received 5 single-donor IUBTs between 20-32 weeks gestation was 3.4 μg/kg (range 0.5-7.9 μg/kg). One donor unit contained 12.9 μg/dL of Pb, resulting in a fetal dose of 7.9 μg/kg, 40 times higher than the estimated IV RfD at 20 weeks gestation. CONCLUSION: This is the first study documenting inadvertent exposure to Hg and Pb from IUBT and quantifying the magnitude of exposure. Screening of donor blood is warranted to prevent toxic effects from Hg and Pb to the developing fetus.

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved from 57 preterm infants at five time points, from birth until 36-weeks postmenstrual age (PMA). GDF15 levels were measured using ELISA in 114 samples. We performed two-sample t-test, correlation and linear regression, logistic regression, and mixedeffects linear models for statistical analysis, and significance was identified when p < 0.05. Contrary to our hypothesis, for every 1-week increase in gestational age at birth, the predicted GDF15 level decreased by 475.0 pg/ml (p < 0.001). Greater PMA was significantly associated with lower serum GDF15 levels (p < 0.001). Interestingly, higher GDF15 levels were associated with a longer need for mechanical ventilation (p = 0.034), prolonged respiratory support need (p < 0.001), and length of hospital stay (p = 0.006). In conclusion, in preterm infants, GDF15 levels show an inverse correlation with gestational age at birth, with higher levels in more preterm babies, and levels trend down postnatally. Furthermore, longitudinal GDF15 levels through 36 weeks PMA predict adverse respiratory outcomes in preterm infants.

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Background Pulmonary interstitial emphysema (PIE) is a pathological state when air escapes from ruptured alveoli and is trapped along the sheaths surrounding the bronchovascular bundle. PIE is not uncommon in infants who require mechanical ventilation and even less common in infants on noninvasive ventilatory support; however, it is extremely unusual in infants in room air. Case Presentation A 2‐week‐old male infant developed worsening tachypnea in the special‐care nursery. The patient was born at 33 weeks' gestation by induced vaginal delivery due to pre‐eclampsia. He required positive pressure ventilation at birth and was admitted to the neonatal intensive care unit on nasal continuous positive airway pressure. On the second day of life, exogenous surfactant was administered via endotracheal tube due to increased oxygen requirement, and, soon after, he was weaned off all respiratory support. After 10 days of stability, he developed tachypnea with diminished air entry on the left side of the chest. Chest radiograph and chest computerized tomography confirmed left‐sided unilateral PIE. The patient was treated conservatively with positional therapy alone. Significant clinical and radiographic improvement was noticed within 4 days; almost complete resolution by 10 days and the infant was discharged 23 days later. At follow‐up at 7 months, the infant was found to be symptom‐free with a normal chest radiograph. Conclusions Traditional management of unilateral PIE generally involves a combination of invasive ventilatory support and positional therapy to break the vicious cycle pathophysiology of PIE. This report focuses on the insidious progression of PIE in nonventilated neonates and describes a nontraditional conservative management strategy for the management of unilateral PIE.

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