Maternal smoking during pregnancy (MSDP) remains an enormous public health concern. However, despite robust links between MSDP and child behavior deficits (e.g., conduct disorder/ externalizing behavior), no large-scale studies have addressed unique effects of maternal smoking on neonatal behavior. We analyzed data from the National Collaborative Perinatal Project to provide the first large-scale community study to investigate effects of prospectively measured MSDP on a clinical neonatal behavior examination. To our knowledge, the present study represents the largest study of examiner-assessed neonatal behavior in smoking-exposed infants; sample size for the present study is nearly ten times larger than all prior studies. We found a significant influence of MSDP on infant irritability and muscle tone. Specifically, neonates exposed to heavy maternal smoking (one pack per day or more) showed greater irritability relative neonates exposed to moderate maternal smoking (less than a pack per day) or unexposed neonates. Neonates exposed to both heavy and moderate maternal smoking were also more hypertonic than unexposed neonates.
There are a number of notable strengths of this study. First, the large sample size, diversity of socio-economic status, and representative nature of the sample support the generalizability of results from the present study. Second, prospective assessment of maternal smoking (at each prenatal visit), prior verification of maternal reports with serum cotinine23
, and decreased social sanctions against smoking during the period of data collection support the validity of maternal smoking reports. Third the unique distribution of maternal smoking (62% smokers with one fourth smoking a pack a day or more) and decreased social sanctions against smoking at the time of data collection allowed for analyses of differential influence of moderate versus heavy smoking and examination of effects of maternal smoking less confounded by socio-economic status (SES) than in more recent samples. Fourth, strict maternal and infant exclusion criteria leading to a healthy sample of infants (no group differences in Apgar scores or gestational age) allowed us to examine effects of maternal smoking relatively unconfounded by health differences in infants. Finally, use of an examiner-administered behavioral examination (rather than maternal report) in this large-scale study allowed for increased validity and objectivity of behavioral outcome data.
Findings from the present study complement smaller-scale studies of MSDP and infant behavior but extend findings to a larger, more generalizable sample. Prior studies from our group have shown unique effects of maternal smoking on arousal/ excitability, difficulty in soothing, hypertonicity, and signs of withdrawal in samples of healthy, full-term infants where smokers and non-smokers were matched on SES, maternal age, and alcohol use.12, 13
Additional studies examining effects of maternal smoking in the context of other drug use have shown effects on cry quality as well as hypertonicity.10, 11
Results from the present study highlight the influence of maternal smoking on infant irritability (confirming prior effects on cry, arousal/excitability and difficulty soothing11-13
) as well as hypertonicity10, 12
in a larger, more generalizable sample. We can articulate several possible mechanisms to explain consistent effects of MSDP on irritability and muscle tension. One possibility is that these outcomes represent acute effects/toxicity of nicotine. A second possibility is that irritability and muscle tension are part of a constellation of symptoms within a nicotine neonatal withdrawal syndrome. Effects on symptoms of abstinence in Law et al.12
, in neonates of smokeless tobacco users32
, and in an intensive study of neonatal nicotine withdrawal over the first five days33
substantiate this possibility across studies and withdrawal scales. Third, effects may represent the initial signs of persistent behavioral dysregulation, leading to long-term behavioral impairments seen in prior studies.6-9
Finally, effects of prenatal nicotine exposure have been shown to be mediated by nicotinic acetylcholine receptors, which may modulate release of numerous neurotransmitters (i.e., serotonin, norepinephrine), brain regions (brain stem, limbic, and cortical regions) and brain systems (arousal, stress systems) that may underlie early regulatory behaviors 34-39
Results are also consistent with prior studies of MSDP and infantile colic (IC)15
, but extend findings to objective examiner-based infant behavioral assessment and to the early neonatal period. It has been theorized that IC and general infant fussiness may reflect more global and persistent difficulties with behavioral control and self-regulation40, 41
. Suggestive of the global nature of the behavioral dysregulation, infants who cry excessively often also experience concurrent difficulties in other areas—e.g., feeding and sleep.42, 43
Parenting deficits may further exaggerate early behavioral differences. The combination of a fussy, tense infant with a smoking mother under higher stress with fewer resources could lead to strained mother-infant interactions during a critical period for maternal-infant bonding.13, 44
This combination could lead to a negative cycle increasing likelihood of further behavioral dysregulation in the infant/child.45
Highlighting the persistence of behavioral dysregulation over development, Wolke40
found that children who described as persistent criers in infancy were more frequently in the borderline clinical range for hyperactivity symptoms and showed more conduct problems and negative emotionality than controls. Thus, although increased irritability and muscle tension may acutely indicate withdrawal or neurotoxic effects, in combination with parenting deficits, may also represent early endophenotypic markers of risk for later behavioral dysregulation.
Although this study is large-scale and rigorous with important clinical and public health implications, we acknowledge two primary limitations. First, the original Graham-Rosenblith sub-study of the NCPP was not designed to examine the influence of maternal smoking; groups were not matched on additional maternal/infant factors that might influence behavioral outcome. However, strict maternal/infant inclusion criteria and statistical control for infant birthweight likely substantially reduced additional pre and perinatal influences on behavioral outcomes. Second, although the Graham-Rosenblith examination was state-of-the-art for its time and a precursor to modern neurobehavioral assessment, more recent neurobehavioral examinations allow for assessment of a broader range of subtle effects of drug exposure.46
However, that we found significant effects of maternal smoking using an early behavioral exam not designed to reveal deficits due to drug exposure highlights the strength of effects.
The present study represents the largest study of examiner-assessed neonatal behavior in smoking-exposed infants. Maternal smoking was measured prospectively in a large community sample with a high proportion of smokers. Results reveal significant influences of maternal smoking on increased infant irritability and hypertonicity. No significant effects or differences were found in response to the respiratory occlusion challenge. That infants exposed to MSDP can be differentiated from their non-exposed counterparts at less than three days old highlights the possibility and importance of very early intervention and prevention efforts. Further research is needed not only to investigate whether these effects are acute or persistent but also to continue to examine trajectories to long-term outcomes.