Photo Credit: Dror Miller
Dr. Keren Agay-Shay

An Israeli nationwide study of more than 600,000 births, led by a researcher at Bar-Ilan University’s Azrieli Faculty of Medicine, reveals consistent links between high and low temperatures and low fetal birth weight, particularly exposure to heat during the second and third trimesters.

Published Wednesday in the journal Environmental Health Perspectives (Low and High Ambient Temperatures during Pregnancy and Birth Weight among 624,940 Singleton Term Births in Israel (2010–2014): An Investigation of Potential Windows of Susceptibility), the study evaluates critical windows of susceptibility to extreme low and high temperatures during pregnancy and fetal growth in a nationwide cohort of 624,940 singleton term births in Israel during the period 2010-2014.

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The study was led by Dr. Keren Agay-Shay, Director of the Health & Environment Research (HER) Lab at the Azrieli Faculty of Medicine of Bar-Ilan University, together with researchers from Bar-Ilan’s Department of Geography and Environment, the University of Haifa, Ben-Gurion University, the Israel Meteorological Service, and ISGlobal, Universitat Pompeu Fabra and CIBER Epidemiologia y Salud Publica, all located in Spain.

The researchers collected, mapped, modeled, and analyzed data on all recorded live births, residential information at the time of birth, and outdoor temperatures throughout the pregnancy. They subsequently divided the country into three climatic zones and performed a statistical analysis comparing all the data during the days, weeks, and trimesters throughout the pregnancy.

Recorded live births
Birth certificate data for all live births were obtained from the National Birth and Birth Defect Registry in the Ministry of Health. These data include infant birth outcomes, parental sociodemographic characteristics, and residential address at the time of birth.

Mapping residential information
Birth addresses were geocoded, or converted into geographic coordinates, using geocoding services such as HERE and Google, and the Israeli property-mapping database GZIRNET. Eighty percent (80%) of all birth addresses at the home or street level were geocoded. The remaining 20% was geocoded at the settlement level. This 20% comprised births to women with no street address who live in small, non-urban settlements, such as local councils, villages, community settlements, and kibbutzim, as well as births with street address data missing.

Hot, cold, and in between
Daily temperatures were estimated, from a fine resolution scale (one-hour and one-square kilometer resolution) spatiotemporal model, based on data from the Israel Meteorological Service. Maternal residence address at birth, as well as the estimated date of last menstrual period, were used to assign estimates of daily mean, minimum and maximum temperatures during each day of pregnancy.

Climate zone divisions
Israel’s highly variable climate, determined by altitude, latitude, and proximity to the Mediterranean Sea, was classified into three climatic zones: Mediterranean (characterized by a dry, hot summer), and semi-arid and desert/arid, both characterized by dry climate and hot temperatures.

Statistical analysis
For each zone, average daily temperatures during various time periods, such as days, weeks, trimesters, and entire pregnancy were converted into percentiles based on the distribution among all women in the cohort who resided in the climatic zone. This was categorized into centiles.

Next, the researchers performed the statistical analysis and evaluated the associations between temperature centiles and birth weight adjusting for the newborn’s ethnic-religious group, sex, and maternal marital status, origin, age, education, socioeconomic class, and employment status.

Results
Consistent associations were observed between high and low temperatures and fetal birth weight. The strongest links were observed during the second, and particularly the third, trimester for heat and cold.

Analysis of associations between term means birth weight and zone-specific temperature percentiles for all three climate zones combined indicated inverse U-shaped associations, such that the coldest and warmest temperatures were associated with lower term mean birth weights than were temperatures near the middle of each distribution.

The inverse U-shaped pattern was evident based on the average temperature for the pregnancy as a whole. Exposure during pregnancy: compared with women exposed to average temperatures in the 41-50th percentile range, those women exposed to cold temperatures (equal to or below the 10th percentile) had a lower estimated mean birth weight of 56g (95 CI%: –63g, –50g) and those exposed to hot temperatures (above the 90th percentile) had lower estimated mean birth weight of 65g (95 CI%: –72g, –58g).

Trimester-specific associations also showed inverse U-shaped patterns, with the strongest associations estimated for extreme temperatures during the third trimester. Inverse associations between term birth weight and the coolest and warmest temperatures were also significant for the first and second trimesters but were weaker than corresponding estimates for the third trimester.

Analysis and recommendations
“Our study demonstrated the significant associations between exposure to high and low outdoor temperature and birthweight in all term births born in Israel during five years. Lower birthweight may indicate abnormalities in intrauterine growth and is a risk factor for morbidity during early childhood and over the entire life course,” says Dr. Keren Agay-Shay, Director of the HER Lab at the Azrieli Faculty of Medicine of Bar-Ilan University. “In our study, we used a novel high-resolution spatiotemporal model that was not used previously. The patterns of associations were consistent when stratified by urbanicity and geocoding hierarchy when estimated for daily minimum and maximum temperatures, when exposures were classified based on temperature distributions in 49 natural regions, and when estimated for all live births (including preterm births and those with birth defects),” adds Agay-Shay.

The identification of susceptible windows during pregnancy may clarify underlying mechanisms and potential strategies to reduce risks in pregnant women exposed to extreme temperatures. Study estimates suggest a potential window of vulnerability to cold from 3-36 weeks, with the strongest association during week 36, and potential windows of vulnerability to heat from weeks 3-9 and 19-34.

Due to increasing temperatures resulting from climate change, the researchers stress that public health organizations are advised to develop strategies to address these challenges on a national, as well as a community, level. Additionally, identifying windows of vulnerability to temperature can assist clinicians in constructing and refining the set of recommendations they provide to pregnant women.

This research was supported by a grant from the Israel Science Foundation.

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