The extent of the impact of the combined use of alcohol and nicotine, as well as other drugs, during pregnancy on infant deaths and the lifelong health prospects of surviving children is only now becoming clear, thanks to long-term follow-up research from the Safe Passage Study (SPS).

“It shows that the synergy between combined substance use contributes to major later-life problems such as diabetes, metabolic syndrome, and high blood pressure, which are linked to heart attacks and strokes later in life,” says Prof Hein Odendaal, professor emeritus in the Department of Obstetrics and Gynaecology at the Faculty of Medicine and Health Sciences, Stellenbosch University (SU).

The study further reveals that poor socio-economic conditions such as poverty, limited education, and weak job and future prospects are major risk factors for combined substance use. “This socio-economic tragedy in many of our communities must be urgently addressed — not only to reduce infant deaths but also to mitigate the long-term health problems of surviving children, which can determine their entire emotional and physical life trajectory,” Odendaal emphasises.

The SPS is the largest international long-term, prospective study of its kind in the world. It sheds light particularly on the synergistic effect of the combined use of nicotine and alcohol on foetal development, stillbirths, and sudden infant death syndrome (SIDS) — but also on the long-term health problems that manifest in surviving children and are expected to persist into adulthood.

The study was funded by the US’ National Institutes of Health (NIH) and preparations began in 2006. Participant recruitment took place between 2009 and 2016, and long-term follow-up research in South Africa has since been conducted by SU and the University of Cape Town (UCT). The SPS was a joint international effort, also involving researchers from the University of the Western Cape (UWC), Harvard University, the Boston Children’s Hospital, and the Universities of North and South Dakota in the US.

Odendaal, who led the South African arm of the study, explains that more than 12,000 pregnancies were followed in two Cape Town suburbs, and in North and South Dakota in the US, up until the children were one year old.

“This study is unique because we collected the data prospectively during pregnancy and compared it with the health data of the mother, the foetus, and later the baby and young child. Follow-ups using electroencephalograms (EEGs) and magnetic resonance imaging (MRIs) focus on long-term outcomes. A further study at SU is underway, and additional follow-ups are planned for 2026.”

In the original study, pregnant women were questioned at different stages about their alcohol and nicotine use during the previous month; daily intake was recorded, and non-users served as the control group. The impact of these substances on infant deaths, breathing regulation, and vital functions was assessed, while follow-up research examined child development long after birth and into adulthood.

An analysis of data from 4,926 South African pregnant women showed that only 17.8% used no substances, 16.7% used alcohol only, 17.5% used nicotine only, and 36.6% used both alcohol and nicotine.

Infant deaths

The latest findings show the extent of combined exposure to alcohol and nicotine on the risk of SIDS. “This increased the risk of SIDS nearly fifteenfold, compared to a sixfold increase from nicotine use alone and a more than fourfold increase from alcohol use alone,” says Odendaal.

The risk of stillbirths was nearly twice as high in mothers who used nicotine, but almost three times higher in those who used both nicotine and alcohol.

A significant association was also found between a serotonin defect in the brainstem of babies who died from SIDS (see accompanying article).

Placental health

Analysis of 5,809 pregnancies showed that blood flow in the uterine artery and umbilical artery—two main vessels involved in foetal nourishment and growth—was significantly reduced when women used large amounts of nicotine and alcohol, says Odendaal.

The incidence of placental abruption, one of the leading causes of stillbirths at Tygerberg Hospital, was significantly higher among nicotine users. Among women who used alcohol only, there was no increased risk of abruption. The incidence was 0.11% in the 875 women who used neither nicotine nor alcohol (the control group), but 1.25% among the 2,804 women who used even small amounts of both nicotine and alcohol.

Foetal growth, as measured by ultrasound, was also significantly restricted by nicotine and alcohol use.

Health prospects

The effects of prenatal alcohol and nicotine exposure extend far beyond birth, Odendaal emphasises. In the study, about 500 children were evaluated for neurocognitive development and behaviour at age four. When mothers had consumed high levels of alcohol, their children struggled to perform simultaneous or sequential tasks, scored lower in language and sensorimotor areas, and showed more attention and general developmental problems.

Furthermore, the inner two layers of the carotid arteries (which supply the brain with blood) were thicker in children exposed to nicotine and alcohol, indicating a higher risk of hypertension later in life. The kidneys and pancreas were significantly smaller when mothers had used nicotine, suggesting an increased risk of hypertension and diabetes, respectively, later in life.

Brain health

Further MRI follow-ups of 313 children revealed that prenatal exposure to nicotine caused a reduction in the area of the brain critical for executive functioning and processing of reward and punishment. Underdevelopment of this brain region could have major implications for children’s ability to regulate social and emotional responses throughout life.

Exposure to alcohol was associated with a reduction in the structure of the medial temporal lobe, a brain area crucial for learning and memory.

Continued research

The findings of the SPS provide compelling evidence of the harmful effects of substance use on foetal and infant deaths, as well as on health outcomes extending into adulthood.

Odendaal highlights the importance of continued follow-up research. In addition to the MRI and EEG studies by UCT and SU, further research at Tygerberg Hospital is still being analysed.

The Department of Psychiatry at SU also plans a follow-up study in 2026 on the synergistic effects of combined alcohol and nicotine use by mothers living in poor socio-economic conditions on the later occurrence of depression and anxiety in adolescents.