The season of conception does not affect whether more boys than girls are born, nor do temperatures in the environment, a large study reveals. Similarly, researchers found no connection with a location’s violent crime level, unemployment rate, or major events like Hurricane Katrina.

But certain chemical pollutants were related to fewer boys being born compared with girls when researchers looked at data for more than 3 million newborns over 8 years in the US and another 3 million born over 30 years in Sweden.

“With data on births in 150 million people in the US over 8 years and 9 million Swedes over 9 years, this is almost surely the largest study to date on the question of environmental factors and their influence on sex ratio at birth,” said Shanna Swan, PhD, who was not affiliated with the research

Variations in the annual sex birth ratio (SRB) — the number of boys born compared with the total birth rate — are well-accepted. Less clear is what things drive these changes.

Although not the first study to look for connections between major events or pollutants in the air, water, and land and the SRB, it is the first to mine two very large electronic medical record databases for answers, senior study author Andrey Rzhetsky, PhD, a professor of medicine and human genetics at the University of Chicago, told Medscape Medical News.

The findings were published December 2 in PLOS Computational Biology.

And even though the SRB did not vary significantly after Hurricane Katrina in 2005, it did after the 2007 shooting at Virginia Tech, Rzhetsky and colleagues found. The SRB was lower than expected 34 weeks after the mass shooting.

Location, Location, Location

The researchers also found that the levels of chemical pollutants “varied remarkably” across different regions of the country. For example, lead in the land was elevated in the Northeast, Southwest, and Mideastern US, but not in the South. Also, the highest levels of total mercury in water samples was found mostly in Eastern states, especially in the Northeast.

Rzhetsky and colleagues mapped the regional differences of many factors, including hydrazine. Hydrazine is a foaming agent used to make pharmaceuticals and agrochemicals and is used as a propellant for spacecraft.

“Hydrazine appears to follow capricious, blotch-like shapes in the eastern US, each blotch likely centered at a factory emitting this pollutant,” the authors write.

To get a more complete picture, the investigators also compared changes in the SRB with data from the US National Oceanic and Atmospheric Administration, US Environmental Protection Agency, Swedish Meteorological and Hydrological Institute, and Statistics Sweden.

They found that aluminium in air, chromium in water, and total mercury levels drove the SRB up. By comparison, lead in soil and areas with a higher renter occupancy were linked to a lower SRB, or a higher proportion of girls being born.

Rzhetsky and colleagues also add to the evidence for a link between polychlorinated biphenyls (PCBs) and the SRB. Previous findings conflict, the authors note.

“Since the sample sizes of the studies published thus far were very small, our PCBs result would have substantially larger statistical power,” they write.

Several pollutants had no significant link to SRB in the study, including levels of lead or chromium in the air, arsenic in the soil, and cadmium in the air or water.

Consistent Findings

That said, the research had limits.

“The magnitude is new in terms of number of births, and the statistical methods are unusually sophisticated, but the conclusions don’t really differ from much of what has been published,” said Swan, a professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai in New York City.

“The takeaway message that many examined exposures are associated with lower — and some with higher — SRBs is not new, but consistent with other, smaller studies,” said Swan, who co-authored a September 2021 study evaluating endocrine-disrupting chemicals and lower birth rates in Asia.

The data on environmental exposures “is, however, quite uneven, and only known at the ecologic and not the individual level,” she said. “We learn, for example, that SRB was significantly reduced…among families living in areas with the highest septile of lead exposure, but also in those among the highest septile of percent renter occupancy.”

“Evaluating these as to mechanism and plausibility is difficult,” Swan said.

More Research Warranted

The mechanism remains unknown, but the investigators suggested that female embryo pregnancies may end early in development, driving the SRB up. Also, male embryo deaths are more common in the late second or third trimester, at which point they would drive the SRB down. A third factor, maternal hormone levels around the time of conception, could also alter the SRB.

The associations between individual factors and SRB changes are just that — associations — not intended to be interpreted as “sex-specific selection mechanisms” causing the differences at this point, the authors noted. Further studies to confirm the associations are needed.

The research is a good stepping-off point for future studies to look closer at the contribution of pollutants like arsenic, lead, cadmium, and more, Rzhetsky said.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.

PLoS Comput Biol. 2021;17(12):e1009586. Full text

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