Perinatal complications associated with maternal tobacco use

Life span studies have shown that the population percentage of left-handers diminishes steadily, so that they are drastically underrepresented in the oldest age groups. Data are reviewed that indicate that this population trend is due to the reduced longevity of left-handers. Some of the elevated risk for sinistrals is apparently due to environmental factors that elevate their accident susceptibility. Further evidence suggests that left-handedness may be a marker for birth stress related neuropathy, developmental delays and irregularities, and deficiencies in the immune system due to the intrauterine hormonal environment. Some statistical and physiological factors that may cause left-handedness to be selectively associated with earlier mortality are also presented.

Left-handedness: a marker for decreased survival fitness.

Cigarette smoking during pregnancy is the single largest modifiable risk for pregnancy-related morbidity and mortality in the US. Addiction to nicotine prevents many pregnant women who wish to quit smoking from doing so. The safety and efficacy of nicotine replacement therapy (NRT) for smoking cessation during pregnancy have not been well studied. Nicotine is classified by the US Food and Drug Administration as a Pregnancy Category D drug. Animal studies indicate that nicotine adversely affects the developing fetal CNS, and nicotine effects on the brain may be involved in the pathophysiology of sudden infant death syndrome (SIDS). It has been assumed that the cardiovascular effects of nicotine resulting in reduced blood flow to the placenta (uteroplacental insufficiency) is the predominant mechanism of the reproductive toxicity of cigarette smoking during pregnancy. Short term high doses of nicotine in pregnant animals do adversely affect the maternal and fetal cardiovascular systems. However, studies of the acute effects of NRT in pregnant humans indicate that nicotine alone has minimal effects upon the maternal and fetal cardiovascular systems. Cigarette smoking delivers thousands of chemicals, some of which are well documented reproductive toxins (e.g. carbon monoxide and lead). A myriad of cellular and molecular biological abnormalities have been documented in placentas, fetuses, and newborns of pregnant women who smoke. The cumulative abnormalities produced by the various toxins in cigarette smoke are probably responsible for the numerous adverse reproductive outcomes associated with smoking. It is doubtful that the reproductive toxicity of cigarette smoking is primarily related to nicotine. We recommend the following. Efficacy trials of NRT as adjunctive therapy for smoking cessation during pregnancy should be conducted. The initial dose of nicotine in NRT should be similar to the dose of nicotine that the pregnant woman received from smoking. Intermittent-use formulations of NRT (gum, spray, inhaler) are preferred because the total dose of nicotine delivered to the fetus will be less than with continuous-use formulations (transdermal patch). A national registry for NRT use during pregnancy should be created to prospectively collect obstetrical outcome data from NRT efficacy trials and from individual use. The goal of this registry would be to determine the safety of NRT use during pregnancy, especially with respect to uncommon outcomes such as placental abruption. Finally, our review of the data indicate that minimal amounts of nicotine are excreted into breast milk and that NRT can be safely used by breast-feeding mothers.

Risks and Benefits of Nicotine to Aid Smoking Cessation in Pregnancy

The respiratory response to hypoxia in mammals develops from an inhibition of breathing movements in utero into a sustained increase in ventilation in the adult. This ventilatory response to hypoxia (HVR) in mammals is the subject of this review. The period immediately after birth contains a critical time window in which environmental factors can cause long-term changes in the structural and functional properties of the respiratory system, resulting in an altered HVR phenotype. Both neonatal chronic and chronic intermittent hypoxia, but also chronic hyperoxia, can induce such plastic changes, the nature of which depends on the time pattern and duration of the exposure (acute or chronic, episodic or not, etc.). At adult age, exposure to chronic hypoxic paradigms induces adjustments in the HVR that seem reversible when the respiratory system is fully matured. These changes are orchestrated by transcription factors of which hypoxia-inducible factor 1 has been identified as the master regulator. We discuss the mechanisms underlying the HVR and its adaptations to chronic changes in ambient oxygen concentration, with emphasis on the carotid bodies that contain oxygen sensors and initiate the response, and on the contribution of central neurotransmitters and brain stem regions. We also briefly summarize the techniques used in small animals and in humans to measure the HVR and discuss the specific difficulties encountered in its measurement and analysis.

The Ventilatory Response to Hypoxia in Mammals: Mechanisms, Measurement, and Analysis

Growth and motor development in fetuses of women with type-1 diabetes. I. Early growth patterns

Maternal smoking causes fetal hypoxia: Experimental evidence

Respiratory movements in fetal rhesus monkeys.

Simulanteous recordings of the fetal electrocardiogram (FECG) and Doppler cardiogram (DCG) were employed during labor to study the systolic time intervals of the fetal cardiac cycle. Clarity of the DCG signal was enhanced by means of a 600–2000 Hz bandpass filter. Experiments using a model to simulate valvular motions demonstrated that variations in time delay of the Doppler signal resulting from differences in the angle between ultrasonic beam and direction of valve motion were small and unlikely to invalidate comparisons based on the DCG. The Q-Ao interval, corresponding to the pre-ejection phase of the cardiac cycle, was found to be independent of heart rate. This interval appeared to increase with increasing fetal age. In normal fetuses of 38–40 weeks' menstrual age, the Q-Ao interval was 70.0 ± 2.4 msec. The Ao-Ac interval, corresponding to ventricular ejection time, increased as heart rate decreased from 180 to 115 beats/min in normal fetuses. There was no further prolongation of Ao-Ac as the heart rate fell below 115 beats/min. The Q-Ao interval was prolonged in each of 8 fetuses with abnormal FHR patterns.

Yuji Murata

Papers

Maternal smoking causes fetal hypoxia: Experimental evidence

Respiratory movements in fetal rhesus monkeys.

Systolic time intervals of the fetal cardiac cycle.

Systolic time intervals of the fetal cardiac cycle.

Effect of acute hypoxemia and respiratory acidosis on the fetal heart rate in monkeys.