Fetal nicotine syndrome: effects and clinical manifestations

Fetal Alcohol Syndrome

NIP in the BUD

Fetal Nicotine Syndrome

Nicotine has been linked to many adverse conditions affecting fetal development and other disorders later in life. Many previous studies established that smoking accounts for sudden infant death, structural, cardio-respiratory and functional dysfunctions of the fetus as well as low weight and preterm births. Some studies connected tobacco smoke with the failure to conceive and behavioral problems later in life. Pharmacological and non-pharmacological therapies are in place for the cessation of smoking. Public policy, community efforts and the media have waged a successful campaign against it with a few measures left needed to fill some gaps in regulation.

Background

Fetal nicotine syndrome is a malformation complex in pregnant women who smoke 5 cigarettes a day and which affects their infants (De Ruvo, 2009). Nicotine has long been the prime suspect linking maternal cigarette smoking during pregnancy and sudden infant death syndrome or SIDS (Eugenin et al., 2008 p 13907). SIDS is a recognized leading cause of death among infants in developed countries. Causes are still unknown but most evidence attributes it to the respiratory failure. Nicotine is a neuroteratogen content of tobacco, blamed for cardio-respiratory dysfunctions in infants during pregnancy. Nicotine moves from the mother to the placenta and into the fetus. It then interacts with functional nicotine receptors. Earlier studies on animals found that prenatal nicotine causes hypoventilation, increases the likelihood of sleep apnea and reduces hypoxia-induced ventilatory reflexes. This present study used pregnant mice to determine the effect of nicotine in unborn mice. Results showed that exposure to nicotine reduced the unborn mice's respiratory rhythm and reduced their central chemoreception. The ventilatory failure is similar to that in SIDS (Eugenin et al., 2008 pp 13908-17).

History

The Developmental Origins of Health and Disease or DOHaD suggest that fetal adaptations in the womb during the developmental stage influence the structure and function of organs (Swanson et al., 2009 p 391). A review of environmental exposures, which can lead to fetal mal-adaptations, was conducted on tobacco smoke, anti-depressant medications and shortage of folic acid. The DOHaD approach was used to determine and explain the long-term effects of the exposures. The approach was drawn from the hypothesis advanced by David Barker through his published observations in 1986, 1989 and 1993. It assumes that a pregnant woman's exposure to stress or toxins, the manner of feeding given to the infant and how fast he grows determine his risks for chronic disease in adult life. Increasing evidence points to the influence of events during the earliest stages of development of the fetus to vulnerability to certain disorders. These disorders include diabetes, cardiovascular disease, asthma, cancers, osteoporosis and neuro-psychiatric conditions (Swanson et al. pp 392-394).

Earliest research dating back in 1957 observed that women who smoked during pregnancy suffered from preterm birth at 11% (Swanson et al., 2009 p 394). This was twice the rate of non-smoking women. Debates ensued for decades on whether the association was causal. In 1992, more findings on lifestyle factors and their effects on pregnancy offered greater evidence to the observation than mere causal association for smoke-related stunted fetal growth. The findings said that tobacco smoke can bring on chronic hypoxia from increased placenta resistance, decreased uterine blood flow, and increased carboxymemoglobin. Smoking can also lead to under-nutrition by suppressing the appetite and food consumption. The National Collaborative Perinatal Project of Births from 1960 to 1966 documented pregnancy outcomes as detrimental effects on neonatal behavior, underweight or obesity, and complications of diabetes or hypertension. This was bolstered by the results of interventions, such as the Generation R Study, on 7,098 women in Rotterdam. It revealed no abnormal effects on infant birth weight in women who stopped smoking at the start of pregnancy. Those who stopped after 32 weeks increased gestational age and reduced preterm birth. Those who stopped before 15 weeks prevented preterm births in comparable levels as non-smoking mothers. These suggested that maternal smoking affects fetal growth and gestation in the late stages of pregnancy. The study also observed that many pregnant women continue to smoke despite these findings and warnings (Swanson et al. pp 393-397).

The Surgeon General's Office report and a recent meta-analysis investigation said that secondhand smoke reduces birth weight, although it does not affect gestation or increases the risk of preterm birth (Swanson et al., 2009 p 398). According to earlier studies, prenatal environmental tobacco smoke and maternal smoking during pregnancy raised the likelihood of neuro-developmental and behavioral disorders in fetuses in later life. Prominent among these disorders is attention deficit hyperactivity disorder or ADHD, which is 2.5 times for children exposed to prenatal environmental tobacco smoke. Programs to suppress environmental tobacco have been introduced in some countries. But these have not been effective because of their high public health costs (Swanson et al. pp 399-402).

Environmental Toxins

Heavy metals, like lead and mercury, organic solvents, alcohol and ionizing radiation are confirmed environmental teratogens (Gardella & Hill, 2000). Exposure to them can lead to pregnancy loss. Suspected teratogens include caffeine, cigarette smoking, insecticide and hyperthermia, the impact of which is still unknown. A teratogen is a substance, organism, or physical agent, which produces a permanent structural or functional abnormality, or causes growth retardation or death in an embryo or fetus when exposed prenatally. Teratogens include radiation, infections, maternal metabolic imbalances, drugs, environmental chemicals, hypoxia, hyperthermia, trauma and surgical procedures. Teratogens produce structural defects, spontaneous abortion, growth retardation, microcephaly, major and minor malformations, metabolic dysfunctions, cognitive dysfunctions or disability, altered social behavior, malignancy, reduced fertility, increased perinatal sicknesses and altered offspring sex ratios (Gardella & Hill).

Cigarette smoking decreases fertility (Gardella & Hill, 2000). It also increases the incidence of spontaneous abortion, abruptio placentae, placenta previa and bleeding during pregnancy and premature rupture of placental membranes, low birth weight, and overall mortality from all causes, specifically SIDS. The connection between spontaneous abortion and maternal smoking has not been accurately established. But current studies strongly suggest that 10-20 cigarettes a day pose a relative risk of miscarriage at a ratio of 1.1-1.3. A study of 1,500 karyotyped spontaneous abortions found that 50% of the women smoked. A large retrospective study of more than 47,000 women also showed that spontaneous abortion occurred in those who smoked more than 10 cigarettes a day. The teratogenicity of environmental factors depends on the fetal gestational age at the time of exposure, amount of toxin reaching the fetus, duration of exposure, impact of other factors to which the mother and the fetus are exposed, genetic differences between them, and interrelationship between frequency of exposure and effect, and the adverse outcome, such as spontaneous abortion (Gardella & Hill).

Preterm Births and Nicotine

Psychological social stress and increased risk of preterm birth have been associated although the connection has not been explained (Denney et al., 2008 p 625). Clinical depression has been reported in 16% of pregnant women and 35% of them presented depressive symptoms. The incidence of preterm birth seemed to increase with depression. Depression, in turn, has been associated with an increase in smoking as well as drugs and alcohol. Cigarette smoking has been found to increase the risk of preterm birth to less than twofold. The in vivo effects of thousands of chemical agents in cigarette smoke have yet to be understood to shed light to the connection. But at present, nicotine and carbon monoxide are known to be powerful vasoconstrictors. They are also associated with placental damage and sub-optimal utero-plancental blood flow. These effects depress fetal growth and preterm deliveries caused by abruption and intrauterine growth restriction. Smoking may also elicit a systemic inflammatory response and spontaneous preterm birth through the inflammatory response and induce labor (Denney et al. pp 626-638).

Health Effects

Tobacco smoke affects all facets of fertility in both genders and influences a couple's inability to have children (Cooper & Moley, 2008 p 204). Women are more potentially vulnerable to environmental toxins like tobacco smoke on account of their complex reproductive cycle. The negative effects can seep in into any part of the reproductive process -- ovulation, fertilization, movement of gametes and embryos, and implantation and throughout the duration of pregnancy. Abundant data reflect on the impact of tobacco smoke throughout the entire in vivo fertilization process, which can extend even if the effect is transient. Increased embryo toxicity, congenital abnormalities, behavioral disorders, decreased fertility and link with adult disease call for prompt action. The reduction of infertility is now a national health objective of the Healthy People 2010, a response to that call. Preventing it by identifying and addressing dangerous lifestyle habits is far better than treating it (Cooper & Moley pp 211-212).

Tobacco smoke consists of more than 4,000 chemicals, many of which are carcinogenic and dangerous toxins (Cooper & Moley, 2008 p 205). Among these are nicotine, tar, polycyclic aromatic hydro-carbons, metals, carbon monoxide and hydrogen cyanide, which are associated with many disease conditions. Both active smoking and secondhand or passive smoke have been primary targets of health care interventions. Secondhand smoke is side-stream smoke from the burning end of a cigarette. Mainstream smoke is exhaled from a smoker. Some experts say that side-stream smoke can emit higher levels of toxins than mainstream smoke. In response to these new reports, the Environmental Protection Agency classified secondhand smoke as a carcinogen because of its harmful effects on the health of both adults and the children of smokers. In addition, a lot more about the harm of other substances in tobacco smoke remains unknown (Cooper & Moley pp 206-209).

Both active and passive smoking can potentially harm almost every organ of the body (Cooper & Moley, 2008 p 209). Smoking has been linked to cardiovascular disease, cancer, stroke and chronic lung disease. Health costs are enormous to public health in terms of increased deaths, the nature of the addition, and the overall medical expenses and indirect costs. A recent survey of 388 women showed that not many of them associate smoking with miscarriage, ectopic pregnancy and infertility at 95-99%. A secondary analysis of the 1995 National Survey of Family Growth identified lifestyle factors linked with infertility among 824 women-respondents. These factors were increasing age, previous ectopic pregnancy, current smoking, obesity and health status. The study also revealed that active smoking by either partner delays conception at 54%. Although some women decide to quit smoking, they remain exposed passive smoke if their partners continue smoking (Cooper & Moley pp 210-212).

Small for Gestational Age

Fetal tobacco syndrome has been shown to lead to infertility at 25%, miscarriage at 25%, ectopic pregnancy at 90%, cleft lip at 35%, abruption and placenta previa at 60%, preterm labor and PPROM at 70%, small for gestational age or SGA at 100-200%, stillbirth at 100% and pre-eclampsia at 30% (McGowan, 2009 p 32). These adverse effects depend on the dose but they are reversible by quitting tobacco. Smoking is considered the single most avoidable risk factor for these risks. Women who stop smoking 15 weeks before delivery have the same low rates of SGA as non-smokers. But those continue to smoke face the risk of preterm births 3 times and SGA 2 times. These mean that harmful effects may be prevented if smoking is stopped early in pregnancy (McGowan p 33).

Maternity care providers must then exert more effort to encourage pregnant smokers to quit smoking early in pregnancy, at least 15 weeks before due date (McGowan, 2009 p 34). These providers should remember that persistent smokers constitute 10-45% of all pregnant women. They face the risk of SGA at two-fold. Most SGA babies are born full-term. These babies are vulnerable and must be detected at term or scanned at 38 weeks, especially in the presence of other risk factors (McGowan pp 35-37).

Smoking and the Risk of Strabismus

A recent prospective, population-based cohort study found that smoking during pregnancy could increase the risk of strabismus in the unborn child (Torp-Pedersen et al., 2010 p 868). The authors of the study examined the effect of in-utero exposure of maternal smoking and the use of alcohol, coffee, and team on the risk of strabismus. They used the medical records of 97,000 children at the Danish National Birth Cohort who could be developing strabismus between 1996 and 2003. From the total, they identified 1,321 cases, which increased proportionately with the number of cigarettes smoked per day (Torp-Pedersen et al. pp 868-869).

Strabismus is a common eye disorder prevalent in 2-6% of children in Western countries (Torp-Pedersen et al., 2010 p 870). Uncorrected strabismus can progress to amblyopia and to permanent blindness. The findings of the cohort study were consistent with those of another study conducted by Chew et al. On more than 39,000 children born between 1959 and 1966. The increase in strabismus risk was also observed in all types of strabismus. In further support, the use of nicotine replacement did not increase the risk. Maternal smoking during pregnancy was observed to limit fetal growth, induce hypoxia through a number of mechanisms, and impair neurodevelopment. The risk was not noted in the first trimester but it increased up to 43% in the first 2 trimesters or in all 3 trimesters, indicating that it tends to occur later in pregnancy. At the same time, maternal smoking renders the fetus vulnerable to toxins, which could affect its development at different periods. The two types of strabismus, esotropia and exotropia, were both linked with maternal smoking. These cases present a deficit in central fusion, which suggests that maternal smoking may affect the brain centers responsible for central fusion in the developing fetus (Torp-Pedersen et al. pp 871-875).

Association with Behavioral Problems

Children who are exposed to prenatal tobacco smoke face a 90% higher risk of abnormal behavior in later life than those not exposed (Ruckinger et al., 2010 p 150). Those post-natally exposed had only a 30% relative risk. The abnormal behavior tends to surface in school age. This was the basic finding of a prospective birth cohort study conducted on 6,000 children born between 1995 and 1998 in two cities in Germany and their parents in determining the relative risk of behavioral problems posed by in utero tobacco smoke. It validated earlier knowledge on the adverse effects of in utero or postnatal tobacco smoke, not only intrauterine growth retardation, SIDS, and asthma, but also of behavioral problems later in life (Ruckinger et al. pp 151-152).

The present study used data derived from the German Infant Nutritional Intervention or GINI, which also conducted a follow-up of the respondents (Ruckinger et al., 2010 p 153). It found tobacco smoke as the most influential exposure that conduces to hyperactivity or inattention in later life, as demonstrated in attention deficit hyperactivity disorder or ADHD. Studies on this subject revealed that in utero tobacco exposure produces more externalizing problems than internalizing problems. It was hypothesized that neurotoxicity occurs through hypoxic effects on the fetal placental unit and teratologic effects of tobacco smoke on the developing nervous system. Studies noted that the fetal brain is protected from many neurotoxicants but not nicotine. Nicotine can cross the placental barrier. It acts as a neurotransmitter on nicotinic receptors ( Koren, 1995 as qtd in Ruckinger et al.). Continuously high nicotine levels change non-adrenaline and dopamine response, which is characteristic of ADHD and demonstrated by the hyperactivity and lack of arousal modulation in animal tests. Smoking also indirectly lowers birth weight and perinatal problems, which contribute to antisocial behavior in later life (Ruckinger et al. pp 153-154).

Tobacco Smoke and Developmental Disabilities (Graff et al. 2007) pp 596-603

The National Research Council and the Oregon Environmental Council emphasized that toxic chemical exposure during the prenatal and postnatal development of a child can have lifetime adverse nervous system effects (Graff et al., 2007 p 596). Lead, for example, can lead to lower intelligence, hyperactivity, learning disabilities and attention disorders. Environmental tobacco smoke, secondhand smoke or ETS comes from the burning end of a cigarette, pipe or cigar. It is exhaled by the smoker and the vapor compounds diffuse through the cigarette wrapper. ETS has more than 4,000 substances, more than 50 of which are considered carcinogenic to humans and animals. Nicotine is one of the components of cigarette smoke and a widely admitted neuro-developmental toxicant. Nicotine is taken into the body when tobacco smoke is inhaled. From the lungs, it is absorbed into the blood stream at a high 92%. It is then broken down into cotinine, a metabolite. Children exposed to ETS have been observed to develop increased respiratory illnesses and symptoms, such as asthma, lower respiratory ailments and serous otitis media. They are more vulnerable to conditions like lipid profiles, cancer, dental caries, infectious illness and SIDS. They tend to be behind in math, reading and visual-spatial reasoning even if their exposure to ETS is at very low levels (Graff et al. pp 597-598).

With the decline of smoking among U.S. adults, children's exposure to ETS also decreased (Graff et al., 2007 p 599). The blood cotinine content in non-smoking children aged 4-17 ranged from 87% to 58% between 1988 and 1994 and between 1999 and 2002, respectively. Children in families living below the poverty line were more likely to live with a smoker (Federal Interagency Forum on Child and Family Statistics, 2005 as qtd in Graff et al.). Children with difficulty or abnormal swallowing and gastro-esophageal reflux are more vulnerable to recurrent aspiration. This, in turn, makes them more susceptible to higher rates of asthma, respiratory inflammation, and respiratory infections. Exposure to ETS in children with developmental disabilities and higher rates of respiratory illnesses puts them at a greater risk than those without developmental disabilities (Graff et al. pp 600-602).

The establishment of a smoke-free environment is recommended to protect children from ETS (Graff et al., 2007 p 602). All family members, visitors and childcare providers should quit smoking. Many health providers lack the knowledge and skills needed to advise parents to stop smoking, however (Graff et al. pp 602-603).

Helping Pregnant Women Quit Smoking

Pregnancy is the best time to encourage smoking mothers to stop smoking in order to protect their fetus and their health (Mendoza & Chaves, 2003). The maternity nurse should find the opportunity to present the enormous health benefits a smoking mother can realize for herself and her fetus through effective coping skills. The Centers for Disease Control and Prevention reported that smoking contributes to the more than 45,000 deaths per year. It is undisputedly the primary cause of preventable sickness, death and large health expense in the United States. In 1995-1999 alone, $157 billion was spent to annual health economic losses relating to smoking. Smoking was linked to annual average of 264,000 deaths among men and 178,00 deaths among women in the United States. They died of lung cancer, ischemic heart disease and chronic airways obstruction (Mendoza & Chavez).

Healthcare providers should inquire into everything about their patients, especially pregnant women and their tobacco use (Mendoza & Chavez, 2003). If the patient is not motivated enough to stop, the healthcare workers should initiate a motivation program. The healthcare worker should discover the reason behind the patient's lack of motivation. She may not be aware of the harmful effects of smoking. She may be apprehensive about withdrawal symptoms or previous relapses. She may not have the financial support. A motivational intervention should be designed for her, which will educate, reassure and motivate her to stop. This intervention is guided by the 5 R's, namely relevance, risks, rewards for quitting, roadblocks to cope with, and repetition (Mendoza & Chavez).