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ScienceWeek
MEDICAL BIOLOGY: ON CHRONIC DISEASE DURING PREGNANCY
The following points are made by R.J. Kaaja and I.A. Greer (J. Am. Med. Assoc. 2005 294:2751):
1) Many physiologic changes occur in pregnancy, beginning early in gestation. These changes allow the mother to tolerate the genetically incompatible fetoplacental unit, adapt her physiologic makeup to nourish and support its development, and prepare her for the hazards of delivery. As a consequence, these complex adaptations render her insulin-resistant, thrombophilic, relatively immunosuppressed, and hypervolemic. Healthy young women generally cope well with these physiologic changes, with pregnancy proceeding uneventfully to term. However, physiologic changes can interact with an inherited or acquired predisposition to disease to precipitate pregnancy complications. Furthermore, many of these complications of pregnancy have common antecedents with a variety of chronic diseases that usually manifest later in life. Pregnancy can unmask a woman's potential for disease, thus providing a window to her long-term health outlook and presenting opportunities for primary prevention.
2) Major physiologic changes occur in pregnancy[1-5]. Healthy women increase plasma volume by 50% by 32 to 34 weeks' gestation. This increase in plasma volume, which is proportional to the size of the fetus, exceeds the increase in red blood cell mass, resulting in a physiologic anemia. In subsequent pregnancies, the increase is greater. This physiologic hypervolemia facilitates delivery of nutrients to the fetus, protects the mother from hypotension, and reduces the hazard of hemorrhage at delivery. The decrease in blood viscosity, resulting from a low hematocrit percentage, creates a lower resistance to blood flow. When this is coupled with the physiologic vasodilatation of pregnancy, a reduction in blood pressure occurs despite an increase in cardiac output. Reduced peripheral resistance may result from a relative refractoriness to the constrictor actions of angiotensin II.[1] The mechanism is not fully established, but an effective vasodilating "buffer" system with nitric oxide, prostacyclin, and antioxidants may play a role.10-12 Interestingly, before delivery, part of the plasma volume shifts into the extravascular space, allowing "autotransfusion" to compensate for postpartum volume loss.
3) Pregnancy is also characterized by changes in the hemostatic and fibrinolytic systems, resulting in a hypercoagulable state. There are substantial increases in procoagulant factors such as factor VIII, von Willebrand factor, and fibrinogen.[2] Endogenous anticoagulant systems are suppressed through a marked reduction in protein S[3] Fibrinolysis is suppressed through an increase in both plasminogen activator inhibitor 1 from the endothelium and placental-specific plasminogen activator inhibitor 2.[4] These changes, together with the increased blood volume, prepare the mother for the hemostatic challenges of delivery.
4) A degree of glucose intolerance due to increased insulin resistance develops during pregnancy. This facilitates continuous glucose transfer to the fetus even when the mother is fasting. Previously, this effect was attributed to the effects of human placental lactogen, cortisol, human placental growth hormone, progesterone, and prolactin. However, increased free fatty acids, peroxisome proliferator-activated receptors, leptin, tumor necrosis factor {alpha}, adiponectin, and resistin have all been implicated in the insulin resistance of pregnancy.[5]
References (abridged):
1. Redman CW. Hypertension in pregnancy. In: De Swiet M, ed. Medical Disorders in Obstetric Practice. 3rd ed. Oxford, England: Blackwell Science; 1995:182-225
2. Stirling Y, Woolf L, North WR, et al. Haemostasis in normal pregnancy. Thromb Haemost. 1984;52:176
3. Clark P, Brennand J, Conkie JA, McCall F, Greer IA, Walker ID. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Haemost. 1998;79:1166-1170
4. Greer IA. Thrombophilia: implications for pregnancy outcome. Thromb Res. 2003;109:73-81
5. Ryan EA. Hormones and insulin resistance during pregnancy. Lancet. 2003;362:1777-1778
J. Am. Med. Assoc. http://www.jama.com
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PUBLIC HEALTH: ON SMOKING DURING PREGNANCY
The following points are made by T.J. Matthews and C.C. Rivera (Morb. Mort. Wkly. Rep. 2004;53:911-915):
1) Cigarette smoking during pregnancy adversely affects the health of both mother and child. The risk for adverse maternal conditions (e.g., premature rupture of membranes, abruptio placentae, and placenta previa) and poor pregnancy outcomes (e.g., neonatal mortality and stillbirth, preterm delivery, and sudden infant death syndrome) is increased by maternal smoking.(1-3) Infants born to mothers who smoke weigh less than other infants, and low birthweight (less than 2500 grams) is a key predictor for infant mortality.(1,2,4) Infertility and conception delay also might be elevated by smoking.(1)
2) National health objectives for 2010 target an increase in cessation to 30% among pregnant smokers during the first trimester and abstinence from cigarettes by 99% of women giving birth.(5) To assess progress toward these goals, CDC analyzed state-specific trends in maternal smoking during 1990-2002 by using data collected on birth certificates.
3) Whereas participating areas observed a significant decline in maternal smoking during the surveillance period, 10 states reported recent increases in smoking by pregnant teens. Although the widespread public health message to abstain from smoking during pregnancy has helped decrease maternal smoking, to reduce prevalence further, implementation of additional interventions are required.
4) In 2002, smoking during pregnancy was reported by 11.4% of all women giving birth in the US, a decrease of 38% from 1990, when 18.4% reported smoking(3). From 1990 to 2002, all 44 states (and DC) with comparable data for the entire observation period reported significant declines in maternal smoking. However, the declines were variable, ranging from 5.8% in West Virginia (from 27.8% in 1990 to 26.2% in 2002) to 68.0% in Massachusetts (from 25.3% in 1990 to 8.1% in 2002).
5) Since 1990, maternal smoking for females aged 15-19 years has fluctuated. Every year from 1996 through 2001, these mothers had the highest percentage of smoking during pregnancy than any other age group.(3) However, in 2002, the percentage of maternal smokers aged 15-19 years (16.7%) was the same as that for women aged 20-24 years, with the highest percentage observed among women aged 18-19 years (18.2%).
6) Of 45 states (and DC) where maternal smoking percentages were calculated for teen mothers during both 1990-1991 and 1995-1996, a total of 34 states had significant declines. Of the 45 reporting states, DC, and NYC, where maternal smoking percentages could be calculated for teen mothers for both 1995-1996 and 2001-2002, a total of 16 states and NYC had significant declines, but 15 states had significant increases for teen maternal smoking. Of these 15 states, 10 had a complete trend reversal from a significant decrease from 1990-1991 to 1995-1996 to a significant increase from 1995-1996 to 2001-2002.
References (abridged):
1. US Department of Health and Human Services; Public Health Service. Women and smoking: a report of the Surgeon General. Washington, DC: Office of the Surgeon General; 2001
2. Mathews TJ, Menacker F, MacDorman MF. Infant mortality statistics from the 2001 period linked birth/infant death data set. Natl Vital Stat Rep. 2003;52:1-28
3. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Munson ML. Births: final data for 2002. Natl Vital Stat Rep. 2003;52:1-113
4. Adams EK, Miller VP, Ernst C, Nishimura BK, Melvin C, Merritt R. Neonatal health care costs related to smoking during pregnancy. Health Econ. 2002;11:193-206
5. US Department of Health and Human Services. Healthy people 2010 (conference ed, in 2 vols). Washington, DC: US Department of Health and Human Services; 2000
Centers for Disease Control and Prevention http://www.cdc.gov
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EFFECTS OF MATERNAL CIGARETTE SMOKING
The following points are made by X. Wang et al (J. Am. Med. Assoc. 2002 287:195):
1) In the US, 65 percent of all infant deaths occur among low-birth-weight infants (less than 2500 grams), with such infants accounting for 7.6 percent of all live-born infants. The etiology of low birth weight is largely unknown, but both environmental and genetic factors may play a role. Numerous studies have demonstrated that maternal cigarette smoking during pregnancy is associated with reduced birth weight or increased risk of low birth weight.
2) In 1997, 13.2 percent of US women reported smoking cigarettes during pregnancy. Maternal cigarette smoking is identified as the single largest modifiable risk factor for intrauterine growth restriction in developed countries. However, not all women who smoke cigarettes during pregnancy have low-birth-weight infants. The reason for this variability is largely unknown, but may be related to maternal genetic susceptibility.
3) Tobacco smoke contains approximately 4000 compounds. The most important carcinogens in tobacco smoke are polycyclic aromatic hydrocarbons, arylamines, and N-nitrosamines. The ability of an individual to convert toxic metabolites of cigarette smoke to less harmful moieties is important for minimizing the adverse health effects of these compounds. Using polycyclic aromatic hydrocarbons (PAHs) as an example, the metabolic processing of these compounds in humans involves 2 phases: a) an activation process, in which the inhaled hydrophobic PAHs are converted mainly via aryl hydrocarbon hydroxylase activity into hydrophilic reactive electrophilic intermediates that can bind covalently to macromolecules, especially to DNA. These intermediates may be more toxic than the original form; b) a detoxification process, in which these metabolic intermediates are detoxified by enzymes via transformation into conjugate forms sufficiently polar to be excreted from the body.
4) The authors investigated the correlation between polymorphisms of 2 metabolic genes (CYP1A1 and GSTT1) and the relation between maternal cigarette smoking and infant birth weight. 741 human mothers were involved in the study. The authors report that maternal CYP1A1 and GSTT1 genotypes modified the association between maternal cigarette smoking and infant birth weight, indicating an interaction between metabolic genes and cigarette smoking.
J. Am. Med. Assoc. http://www.jama.com
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