Prenatal Care in Combination with Maternal Educational Level Has a Synergetic Effect on the Risk of Neonatal Low Birth Weight: New Findings in a Retrospective Cohort Study in Kunshan City, China

<div><p>Objectives</p><p>To investigate the dose-response relationship and synergetic effect of the maternal educational level and two measures of prenatal care on neonatal low birth weight (LBW) risk.</p><p>Methods</p><p>Data were derived from the Perinatal Health Care Surveillance System (PHCSS) from January 2001 to September 2009 in Kunshan City, Jiangsu province, eastern China, which included data on 31412 women with a normal birth weight delivery and 640 women with a LBW delivery. Logistic modelling was performed to estimate the association including the joint effects with odds ratio (OR) and 95% confidence interval (CI) between the prenatal care measures and LBW risk after adjusting for the potential confounders. The dose-response relationship between the number of prenatal care visits and the risk of LBW was investigated by modeling the quantitative exposure with restricted cubic splines (RCS).</p><p>Results</p><p>There was a significant synergetic effect on the LBW risk between maternal educational attainment and the number of prenatal care visits (χ² = 4.98, <i>P</i> = 0.0257), whereas no significant maternal educational attainment interaction was found with the week of initiation of prenatal care after adjusting for relevant confounding factors (χ² = 2.04, <i>P</i> = 0.1530), and the LBW risk displayed a ‘U-shape’ curve tendency among the different number of prenatal care visits (<i>P</i> for nonlinearity = 0.0002) using RCS. In particular, the ORs were approaching the curve’s bottom when the women had 9 or 10 prenatal care visits. Comparing with 5 prenatal care visits, the ORs and 95%CI of LBW risk for 7, 9, 11 and ≥13 visits were 0.92 (0.82–1.03), 0.50 (0.38–0.66), 0.62 (0.47–0.82), and 0.99 (0.61–1.60), respectively.</p><p>Conclusions</p><p>Our findings suggest that appropriate prenatal care, in combination with a higher maternal educational level, can produce a protective interaction effect on LBW risk. Reasonable health resource assignment for different social statuses should be taken into account by policy-makers in developing countries.</p></div

Flow chart.

<p>Flow chart.</p

Baseline characteristics of pregnant women and neonates according to the number of prenatal care visits^*.

<p>*Data are the mean ± SD, median (p25–p75) or n (%) values otherwise indicated. So is <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113377#pone-0113377-t002" target="_blank">Table 2</a>.</p>a<p>missing 796, ^bmissing 4672, ^cmissing 611,^dmissing 745.</p><p>Baseline characteristics of pregnant women and neonates according to the number of prenatal care visits^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113377#nt101" target="_blank">*</a>}.</p

Baseline characteristics of pregnant women and neonates according to the week of initiation of prenatal care.

a<p>missing 796, ^bmissing 4672, ^cmissing 611, ^dmissing 745.</p><p>Baseline characteristics of pregnant women and neonates according to the week of initiation of prenatal care.</p

The LBW risk estimation associated with the prenatal care and educational level.

abc<p>All the three models were adjusted for maternal age, gestational weight gain, BMI at the first pregnancy visit, gestational age, pregnancy-induced hypertension (missing 796), maternal job (missing 4672), and neonatal sex, prenatal care institutions (missing 745). The week of initiation of prenatal care, the number of prenatal care visits and maternal educational attainment (missing 611) were adjusted mutually.</p><p>Hosmer-Lemeshow goodness-of-fit test for each multiple regress model: ^a χ² = 22.99, <i>P</i> = 0.0034; ^b χ² = 22.65, <i>P</i> = 0.0038; ^c χ² = 20.84, <i>P</i> = 0.0076.</p><p>The LBW risk estimation associated with the prenatal care and educational level.</p

Activation of MTOR in pulmonary epithelium promotes LPS-induced acute lung injury

<p>MTOR (mechanistic target of rapamycin [serine/threonine kinase]) plays a crucial role in many major cellular processes including metabolism, proliferation and macroautophagy/autophagy induction, and is also implicated in a growing number of proliferative and metabolic diseases. Both MTOR and autophagy have been suggested to be involved in lung disorders, however, little is known about the role of MTOR and autophagy in pulmonary epithelium in the context of acute lung injury (ALI). In the present study, we observed that lipopolysaccharide (LPS) stimulation induced MTOR phosphorylation and decreased the expression of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3 β)-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by TLR4 (toll-like receptor 4) signaling. Genetic knockdown of <i>MTOR</i> or overexpression of autophagy-related proteins significantly attenuated, whereas inhibition of autophagy further augmented, LPS-induced expression of IL6 (interleukin 6) and IL8, through NFKB signaling in HBE cells. Mice with specific knockdown of <i>Mtor</i> in bronchial or alveolar epithelial cells exhibited significantly attenuated airway inflammation, barrier disruption, and lung edema, and displayed prolonged survival in response to LPS exposure. Taken together, our results demonstrate that activation of MTOR in the epithelium promotes LPS-induced ALI, likely through downregulation of autophagy and the subsequent activation of NFKB. Thus, inhibition of MTOR in pulmonary epithelial cells may represent a novel therapeutic strategy for preventing ALI induced by certain bacteria.</p

Autophagy is essential for ultrafine particle-induced inflammation and mucus hyperproduction in airway epithelium

<p>Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene <i>Becn1</i> or <i>Lc3b</i> displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux.</p