Development of oxygen sensitivity in infants of smoking and non-smoking mothers

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Abstract

Aims: To assess the effect of prenatal cigarette smoke exposure on the postnatal resetting of oxygen sensitivity in term infants. Methods: 15 healthy term infants of smoking mothers (median 10 cigarettes/day) and 16 controls were studied during quiet sleep 1, 3, and 10 days and 10 weeks postnatally. Strain-gauge respiratory trace was continuously recorded. Repeated 15-s challenges with 100% O2 and 15% O2 were presented in randomised order through a face mask. A median of six hyperoxic and six hypoxic challenges per recording were obtained. Breath-by-breath ventilation in a time-window from 20 s before onset of stimulus to 60 s after was extracted. For each infant at each age, the normalised coherently averaged response to hyperoxia and hypoxia was calculated. Mean ventilation at end of the 15-s stimulus was analysed with ANOVA, as were parameters describing a function fitted to each averaged response. Results: During air breathing, smoke-exposed infants had higher respiratory rates and lower tidal volumes than controls. Nicotine concentration in infant hair, measured by gas chromatography, was positively correlated with maternal level of smoking. A long-term development in oxygen sensitivity was demonstrated in both groups. However, neither the time-course nor the magnitude of O2 responses was affected by maternal smoking. Overall, hyperoxia reduced ventilation by 6.3% at day 1, 13.2% at day 3, 29.6% at day 10, and 40.0% at week 10. Transient hypoxia increased ventilation by 3.5%, 3.2%, 6.4%, and 8.8%, respectively, at the four ages studied.

Introduction

Functional arterial chemoreceptors are thought to be crucial in sustaining continuous breathing after birth [1]. In fetal life, both aortic and carotid chemoreceptors are responsive to blood gas changes. After birth, arterial PO2 rises steeply, and electrophysiological recordings in lambs have demonstrated that the oxygen sensitivity range of the peripheral chemoreceptors is adjusted accordingly over 1–2 weeks [2], [3]. A similar resetting of oxygen sensitivity has been shown in the neonatal rat, where ventilatory responses to both transient hyperoxia [4] and acute hypoxia [5] increased during the first few days after birth. In vitro studies of rat carotid bodies indicated that resetting was complete after 1–2 weeks [6].

Resetting of oxygen sensitivity also appears to take place in the human infant, and previous studies have indicated that the process is complete 1 week after birth. Infant ventilatory responses to both hyperoxia [7] and hypoxia [8] were found to increase between birth and day 6–8. In contrast, the response to 100% O2 was similar at 1, 2, and 3 months [9], and hypoxic sensitivity was unchanged between 43 h and 47 days [10]. However, in a study of respiratory oscillations following spontaneous sighs, a stable, mature response was not present until 3–4 months postnatally [11]. This suggests that the maturation of ventilatory responses to blood gas and pH changes may be a more prolonged process.

One mechanism that has been proposed for the shift in chemoreceptor sensitivity range is the rapid change in carotid body dopamine content and turnover that takes place around birth [12], [13]. Nicotine seems to modulate these changes in carotid body transmitters [13] as well as the postnatal development of ventilatory responses to altered inspiratory O2 level [13], [14]. The suggested connection between exposure to cigarette smoke and a disturbance of chemoreceptor development is interesting, since passive smoking increases the risk of sudden infant death syndrome (SIDS) in a dose dependent manner. The risk of SIDS approximately doubles when the mother smokes 1–9 cigarettes/day, while >10 cigarettes/day gives odds ratios of 3–6 [15], [16], [17].

We hypothesised that the development of ventilatory responses to transient changes in O2 might be altered in infants who were chronically exposed to cigarette smoke prenatally. Our study population was healthy infants from normal pregnancies, and the exposure group consisted of infants of mothers who smoked daily. Since even low levels of passive smoking elevates the risk of SIDS, no lower limit of number of cigarettes smoked per day was set. The timing of experiments was chosen to allow detection of both the rapid resetting shortly after birth, and the possible more prolonged maturation of the responses.

Section snippets

Subjects

Eligible for inclusion were healthy term infants with Apgar scores ≥8 at 1 and 5 min and birth weight ≥2500 g. Any maternal chronic illness, receptor active medication during pregnancy, alcohol or illicit drug abuse excluded an infant. Regional Ethics Committee approval and written informed consent from parents were obtained.

Randomly selected infants of women who reported to have smoked ≥1 cigarette per day throughout pregnancy were recruited together with control infants born to non-smokers.

Results

Experiments were carried out between 09:20 and 16:00 h, starting 65 min (range 18–191 min) after a meal. Median duration of quiet sleep that was accepted for analysis in an experiment was 19 min (range 3–34 min). Obtained number of successful stimulation periods were similar in the two groups, as were infants’ ages at the four times of study (Table 2; Mann–Whitney U, P always ≥0.23).

Discussion

In this study of healthy term infants, we found markedly higher fR and lower VT in infants exposed to moderate levels of cigarette smoke during pregnancy. However, neither the magnitude of ventilatory responses to hyperoxia and hypoxia nor the ventilatory strategy applied to achieve the response differed significantly from that in control infants. Our results confirm and extend previous findings of a long-term postnatal maturation of ventilatory oxygen sensitivity in humans. The study also

Conclusion

This study demonstrates that the ventilatory responses to transient hyperoxia and hypoxia continue to develop for several weeks postnatally. Also, our findings indicate that in healthy term infants exposed to moderate levels of maternal smoking, this development is unaffected.

Acknowledgements

S. Søvik holds a combined grant from the Research Council of Norway and the Faculty of Medicine, University of Oslo, Norway. This work was supported by the Norwegian Academy of Science and Letters, the Norwegian SIDS Society, and the Norwegian National Health Association.

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