Preterm Birth, Developmental Smoke/Nicotine Exposure, and Life-Long Pulmonary Sequelae.

This review delineates the main pulmonary issues related to preterm birth, perinatal tobacco/nicotine exposure, and its effects on offspring, focusing on respiratory health and its possible transmission to subsequent generations. We review the extent of the problem of preterm birth, prematurity-related pulmonary effects, and the associated increased risk of asthma later in life. We then review the impact of developmental tobacco/nicotine exposure on offspring asthma and the significance of transgenerational pulmonary effects following perinatal tobacco/nicotine exposure, possibly via its effects on germline epigenetics.

The impact of perinatal nicotine exposure on fetal lung development and subsequent respiratory morbidity.

Maternal smoking during pregnancy remains as a significant public health crisis as it did decades ago. Although its prevalence is decreasing in high-income countries, it has worsened globally, along with a concerning emergence of electronic-cigarette usage within the last two decades. Extensive epidemiologic and experimental evidence exists from both human and animal studies, demonstrating the detrimental long-term pulmonary outcomes in the offspring of mothers who smoke during pregnancy. Even secondhand and thirdhand smoke exposure to the developing lung might be as or even more harmful than firsthand smoke exposure. Furthermore, these effects are not limited only to the exposed progeny, but can also be transmitted transgenerationally. There is compelling evidence to support that the majority of the effects of perinatal smoke exposure on the developing lung, including the transgenerational transmission of asthma, is mediated by nicotine. Nicotine exposure induces cell-specific molecular changes in lungs, which offers a unique opportunity to prevent, halt, and/or reverse the resultant damage through targeted molecular interventions. Experimentally, the proposed interventions, such as administration of peroxisome proliferator-activated receptor gamma (PPARγ) agonists can not only block but also potentially reverse the perinatal nicotine exposure-induced respiratory morbidity in the exposed offspring. However, the development of a safe and effective intervention is still many years away. In the meantime, electropuncture at specific acupoints appears to be emerging as a more practical and safe physiologic approach to block the harmful pulmonary consequences of perinatal nicotine exposure.

Biomolecular effects of JB1 (an IGF-I peptide analog) in a rat model of oxygen-induced retinopathy.

Low-serum IGF-I levels at birth is a risk factor for the development of retinopathy of prematurity in extremely LBW infants. We tested the hypothesis that JB1 (an IGF-I analog) prevents oxygen-induced retinopathy in our rat model. Neonatal rats were exposed to 50% oxygen with brief, clustered, hypoxic (12%) episodes from birth to P14. The pups were treated with s.c. injections of 1) JB1 (1 µg/d) on P1, P2, and P3 (JB1x3); 2) JB1 (1 µg/d) on alternate days from P1 to P13 (JB1x7); or 3) equivalent volume saline. Control littermates were raised in room air (RA) with all conditions identical except for inspired O2. Groups were analyzed after hyperoxia/hypoxia (H/H) cycling at P14 or allowed to recover in RA until P21. Systemic and ocular VEGF, soluble VEGFR-1, and IGF-I; retinal vasculature; and gene profile of retinal angiogenesis were assessed. JB1x3 was more effective with associated increases in sVEGFR-1 and decreased retinal pathologies than JB1x7. We conclude that early short-term exposure to systemic JB1 treatment normalizes retinal abnormalities seen with H/H cycling, an effect that may involve sVEGFR-1.

Effects of combined hyperoxia and cyclooxygenase inhibition in neonatal rat lungs.

We examined the hypothesis that persistent pulmonary hypertension of the newborn (PPHN) associated with ibuprofen is due to alterations in biochemical and molecular regulators of oxidative stress and NO signaling. Newborn rats breathing 50% O2 or room air from the first day of life (P1), received early IP injections of: 1) indomethacin (0.2 mg/kg) on P1 and 0.1 mg/kg on P2 and P3; 2) ibuprofen (10 mg/kg) on P1 and 5 mg/kg on P2 and P3; or 3) saline on P1, P2 and P3, then euthanized on P4; or late treatment on P4, P5 and P6, then euthanized on P7. Lung biomarkers for oxidative stress (8- epi-PGF2a), DNA damage (8-hydroxy-2'-deoxyguanosine) and pulmonary hypertension (ET-1, big ET-1, and total NO) were assessed. Despite timing of the dose and oxygen exposure, both drugs resulted in increased alveolar size. Both drugs had no beneficial effects on oxidative stress. Indomethacin treatment in O2 resulted in higher pulmonary levels of 8-epi-PGF2alpha which was associated with downregulation of most antioxidant genes with early treatment and overexpression of GPX5 and 6 with late treatment. Early and late ibuprofen treatment suppressed hyperoxia-induced NOx production and downregulated iNOS. Postponing treatment had no significant beneficial effects on biomolecular regulators of oxidative stress and NO signaling. The effect of ibuprofen on pulmonary NOx may explain in part, the transient PPHN seen in ibuprofen-treated preterm infants.

Poland-Möbius syndrome and cocaine abuse: a relook at vascular etiology.

This report presents a severe case of Poland-Möbius syndrome with central apnea at birth, ventilator-dependent, and with brainstem calcifications. The newborn had unilateral defect of the right pectoralis muscle, breast, and limb. He manifested bilateral paralysis of the cranial nerves resulting in shallow respiration, apnea, and dysphagia. He finally required tracheostomy and gastrostomy. Maternal history revealed multiple uses of cocaine during the first 3 months of pregnancy. The patient supports the Poland-Möbius combination and the possibility of vascular disruption sequence.