13. Perinatal Factors

INTRODUCTION

This section of the Guidelines provides recommendations to pediatric care providers on management of perinatal factors that predispose children to accelerated atherosclerosis. The section begins with background information on the role of pediatric care providers in perinatal risk exposure and the decision to focus on maternal smoking cessation. This is followed by the Expert Panel's summary of the evidence review. The evidence review and the development process for the Guidelines are outlined in Section I. Introduction and are described in detail in Appendix A. Methodology. As described, the evidence review augments a standard systematic review, whereby the findings from the studies reviewed constitute the only basis for recommendations, with each study described in detail. This evidence review combines a systematic review with an Expert Panel consensus process that incorporates and grades the quality of all relevant data based on preidentified criteria. Because of the large volume of the included studies and the diverse nature of the evidence, the Expert Panel also provides a critical overview of the studies for each risk factor, highlighting those that, in its view, provide the most important information. Detailed information from each study has been extracted into the evidence tables, which will be available at http://www.nhlbi.nih.gov/guidelines/cvd_ped/index.htm. This section ends with the conclusions of the review, grading of the evidence, and the recommendations. Where evidence is inadequate, the recommendations are the consensus opinion of the Expert Panel. References are listed sequentially at the end of the section, with references from the evidence review identified by unique PubMed identifier (PMID) number in bold text. Additional references do not include the PMID number.

BACKGROUND

Increasing evidence links prenatal exposures to adverse health outcomes.^[1]  Perinatal cardiovascular (CV) risk reduction is an area in which pediatric care providers can be effective since they are often the only physicians that a mother sees between pregnancies. The Expert Panel identified three potential areas for consideration:  maternal obesity, choice of neonatal feeding method, and maternal smoking cessation. Maternal obesity is associated with gestational diabetes, higher birth weight, childhood obesity as measured by increased body mass index (BMI), and increased risk of the metabolic syndrome and type 2 diabetes mellitus (T2DM) in offspring.^[2],[3]  However, the Expert Panel could not identify any prepregnancy or postpartum studies addressing maternal obesity in a pediatric health care setting, and more general approaches to preventing or treating obesity in women of reproductive age are beyond the scope of these Guidelines, which are for pediatric care providers. A detailed discussion of childhood obesity is the subject of Section X. Overweight and Obesity. With regard to choice of neonatal feeding method, the CV advantages of breastfeeding as the primary source of nutrition for infants are reviewed in detail in Section V. Nutrition and Diet. The evidence review for this  section therefore focuses on maternal smoking cessation.

OVERVIEW OF THE EVIDENCE ON MATERNAL SMOKING CESSATION

Smoking during pregnancy is strongly associated with fetal growth retardation. Epidemiologic studies show that lower birth weight is associated with central adiposity, insulin resistance, hypertension, T2DM, and increased risk of coronary heart disease decades later.^[4],[5] In most of these studies, lower birth weight probably represents reduced fetal growth rather than shorter gestational duration, although some recent studies suggest that preterm birth also is associated with these adverse outcomes. Among pregnant women who smoke, the rate of low birth weight increases directly as the number of cigarettes/day increases. Despite decades of knowledge of its adverse health effects, cigarette smoking remains common among women of childbearing age, reported at 22–23 percent in 2000, although rates are lower during pregnancy in the United States and other developed countries. Perhaps paradoxically, maternal smoking during pregnancy is associated with increased rates of subsequent obesity in offspring and, in some studies, elevated blood pressure (BP). A recent meta-analysis of observational studies estimated a pooled odds ratio (OR) of 1.50 (95 percent confidence interval (CI) = 1.36–1.65) of obesity among offspring of mothers who smoked during pregnancy compared with those who did not.^[6]

Because pediatric care providers are often the only physicians that a mother sees between pregnancies, these health care professionals have the potential to initiate and support maternal smoking cessation. If successful, such interventions have the potential to reduce not only the harms associated with fetal growth restriction but also the risk of obesity in the next generation. In the evidence review for these Guidelines, there were 2 randomized controlled trials (RCTs) of smoking cessation restricted to the postpartum period, and smoking cessation studies during pregnancy included 3 relevant systematic reviews, 2 meta-analyses, and 11 RCTs. A 2004 comprehensive review by The Cochrane Collaboration included all identifiable smoking cessation trials during pregnancy dating back to 1976. Pooled across 48 trials and including 6 of the 11 RCTs identified by this review, the authors reported that the included interventions resulted in a relative reduction of 6 percent (RR = 0.94, 95 percent CI = 0.93–0.95) in maternal smoking between the intervention and control groups. The subset of 16 trials that provided information on perinatal outcomes showed a mean increase in birth weight of 33 g (95 percent = 11–55 g), along with a reduction in both low-birth-weight babies (pooled relative risk (RR) = 0.81, 95 percent CI = 0.70–0.94) and preterm births (pooled RR = 0.84, 95 percent CI = 0.72–0.98).^[7]  Most trials combined pregnancy-specific education, advice, and reinforcement. The authors of the review noted that an intervention that combined rewards with social support used in two trials led to greater smoking reduction than other strategies. In the five trials that included smoking relapse prevention, the authors did not find that interventions prevented women from resuming smoking in late pregnancy (pooled RR = 0.81; 95 percent CI = 0.63–1.04).

Among the five RCTs published after the most recent systematic review, a majority took place in public clinic settings, with one trial extending the intervention to include the pediatric clinic.^[8],[9],^[10],^[11]  Results were similar to those in the systematic review, with three of four interventions resulting in a decrease in maternal smoking during pregnancy. No study was associated with sustained cessation in the postpartum period, which also was consistent with the systematic review. One trial set in prenatal clinics addressed smoking cessation in pregnant adolescents using an intervention based on cognitive behavior theory.^[12] Subjects were randomized to usual care, the "Fresh Start" or "Fresh Start Plus" intervention programs, with a female friend. Smoking status was assessed by self-report and cotinine levels. At 8 weeks postrandomization, those in the Fresh Start Plus group were significantly more likely to be abstinent than those in the usual care group (OR = 2.106 (0.542, 8.190)); there was no difference between the program alone and either comparison group. However, at 1-year postrandomization, there was no difference in abstinence rates between any of the groups.

Two studies addressed smoking cessation in the postnatal period, with subjects identified via the newborn nursery. The first study in breastfeeding mothers addressed reducing the infant's exposure to passive smoke. Intervention subjects received specific guidance about limiting the infant's exposure to cigarette smoke and a room air cleaner to be placed in the infant's bedroom.^[13]  Tobacco exposure was assessed by nicotine and cotinine levels in breast milk and in infant urine samples. In both the intervention and usual care groups, women smoked twice as much at 2 and 5 weeks postdelivery as they did during pregnancy. Infant urinary nicotine and cotinine levels increased over time in both groups, with no significant difference between the groups at 2, 3, or 5 weeks. A much larger study enrolled 2,901 mothers at the first infant postnatal visit to the pediatric clinic.^[14]  Half of the mothers received the usual advice about limiting smoke exposure at that visit. The other half received specific antismoking guidance at each nonurgent visit in the first 6 months of life, an average of 4 exposures. When babies were age 6 months, there were significantly fewer smokers in the intervention group among both those who had stopped smoking for the pregnancy and those who had continued to smoke. However, this difference was not sustained at 1-year followup.^[15]

CONCLUSIONS AND GRADING OF THE EVIDENCE REVIEW ON MATERNAL SMOKING CESSATION

• The Expert Panel finds that strong evidence supports a benefit for interventions directed at maternal smoking cessation during pregnancy (Grade A). Weaker evidence suggests that these interventions do not prevent relapse postpartum. Trials of cessation in the postpartum period, which would be the most applicable to pediatric providers, are limited in number and suggest that for maternal smoking cessation to be sustained, specific continued support in the pediatric care setting is required.
• No smoking cessation interventions reported any adverse effects related to the interventions (no grade).
• The Expert Panel believes that pediatric care providers can play a role in helping mothers  remain smoke free or quit smoking in the interpregnancy interval. For most women, this interval extended to the early first trimester of any subsequent pregnancy. The pediatric well-child schedule calls for about 10 visits in the first 2 years of life; since mothers attend most visits, the pediatric care provider usually sees women in this period more than any other health care professional. Pediatric care providers often have a sustained relationship with mother and baby, and many already advocate for parental smoking cessation in their efforts to promote a smoke-free environment for children. Pediatric providers and/or their staffs need to be trained to either deliver or refer to a long-term maternal smoking cessation program (no grade).

Table 13–1. Evidence-Based Recommendations for Maternal Smoking Cessation

Grades reflect the findings of the evidence review.
Recommendation levels reflect the consensus opinion of the Expert Panel.
Supportive actions represent expert consensus suggestions from the Expert Panel provided to support implementation of the recommendations.

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