Maternal smoking during pregnancy causes important metabolic and biochemical changes and adaptive responses in the fetus and mother, resulting in an increased incidence of maternal and fetal complications such as intrauterine growth retardation and decreased fetal weight and size [
Erythropoietin is a glycoprotein hormone involved in the regulation of erythropoiesis during fetal and adult life. The only known stimulus for production of erythropoietin is decreased partial oxygen pressure [
This study was undertaken to investigate the effect of maternal smoking on umbilical cord plasma erythropoietin levels as a measure of chronic intrauterine hypoxia. We hypothesized that maternal smoking may cause fetal hypoxia which may cause elevated erythropoietin levels, that is, having a compansatuar effect on blood gas oxygenization values.
This study was a prospective study performed on 60 neonates between November 2009 and April 2010 in a tertiary care center. History of maternal smoking was present with 20 of these neonates. The nonsmoking and smoking mothers had similar mean age (Table
Relation between maternal smoking and neonatal characteristics.*
Nonsmokers | Smokers | ||
Number of subjects | 40 | 20 | |
Maternal age (y) | NS | ||
Number of parities | NS | ||
Duration of gestation (wk) | NS | ||
Birth weight (kg) | NS | ||
Sex of neonate | |||
Male | 23 (57%) | 10 (50%) | NS |
Female | 17 (43%) | 10 (50%) | |
Apgar score | |||
1st minute | NS | ||
5th minute | |||
Cord blood | |||
pH | NS | ||
PO2 (mm Hg) | NS | ||
PCO2 (mm Hg) | NS | ||
Erythropoietin (IU/L) | .001 |
*Data reported as mean
†NS, not significant (
After delivery, a segment of the umbilical cord was clamped and venous cord blood samples were immediately transferred into tubes containing heparin. The serum was separated by centrifugation (4000 rpm for 5 minutes) and stored (−20°C) for 1 month. Erythropoietin levels were measured in duplicate using a chemiluminescent enzyme immunoassay (DPC Immulite EPO kit, Siemens Medical Solutions Diagnostics, Los Angeles, CA).
All the statistical analyses were performed with SPSS 17.0 for Windows (SPSS Inc., Chicago, IL).
Average results for the nonsmoking and smoking groups were compared by using Mann-Whitney rank sum test, and correlations were evaluated with regression analysis. Data were reported as mean
The nonsmoking and smoking mothers had similar average age, number of parities, and duration of gestation, and the neonates from nonsmoking and smoking mothers had similar birth weight and Apgar scores (Table
The finding of elevated cord erythropoietin levels in neonates born from smoking mothers (Table
In 3 recent studies, the correlation between fetal hypoxia and umbilical cord erythropoietin levels was well established, but confounding variables were present [
In the present study, the higher erythropoietin levels from neonates born to smoking mothers and the correlation between the amount of cigarette consumption and erythropoietin levels suggest that smoking has a harmful effect in terms of chronic fetal hypoxia and this hazardous effect of smoking is dose dependent. These findings are consistent with results of previous studies [
Fetal hypoxia, which causes erythropoietin synthesis, may be caused by several mechanisms. Nicotine acts on the cardiovascular system by causing the release of catecholamines into the maternal circulation, resulting in tachycardia, peripheral vasoconstriction, and reduction of placental blood flow that may cause a poor nutritional and oxygenation status for the fetus. Cotinine, a metabolite of nicotine, increases the vasoconstrictive action of prostaglandin E2, and the accumulation of cotinine in the fetal bloodstream may contribute to premature labor and spontaneous abortion among smokers. Furthermore, carbon monoxide produced by cigarettes has strong affinity towards fetal hemoglobin, resulting in hypoxia. A recent report showed a positive correlation between the number of cigarettes smoked per day and the absolute nucleated red blood cell count, another marker of chronic hypoxia, and this also may explain the higher hemoglobin concentrations reported in fetuses of smokers [
Suboptimal fetal oxygenation may cause several perinatal complications in fetuses of women who smoke. Carbon monoxide may interfere with tissue oxygenation by decreasing the blood oxygen transportation capacity and shifting the oxyhemoglobin saturation curve to the left, resulting in hypoxemia and associated growth restriction. Smokers also have deficiencies of some nutrients such as zinc, carotene, and cholesterol. Furthermore, cigarette smoke may be inhaled through the nasal mucosa of infants and affect the growth of infants born to smokers [
The risk of perinatal and obstetric problems is likely related to the number of cigarettes smoked daily and the trimester of pregnancy with the highest exposure. The fetus gains most weight during the second half of pregnancy. The fetus is not just a passive smoker inhaling cigarette smoke involuntarily in an open environment, but it is highly vulnerable and susceptible to the risk of developmental disorders. When a mother smokes, she exposes her fetus to the components of cigarette smoke crossing the placenta and to alterations in oxygen transport, placental metabolism, and maternal metabolism secondary to smoking [
Limitations of the present study include that our study had small group of pregnants and did not compare the different amounts of cigarette consumption.
Nevertheless, the findings of the present study support the practice of encouraging pregnant women to quit smoking. Furthermore, pregnant women who smoke should be monitored closely for signs of uteroplacental insufficiency such as fetal growth restriction.
The authors declare that there is no conflict of interests.