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Updated: May 26, 2026

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants
Published on: March 6, 2018
Associations of ambient temperature exposure with embryonic and early fetal development
Esmée Essers1,2,3,4, Jasmin M de Groot4,5, Naomi Graafland4,6
1ISGlobal, Barcelona, Spain.
Background:
Exposure to heat and cold are associated with adverse birth outcomes, but whether ambient temperature affects embryonic and early fetal development remains unclear. We aimed to examine the association between ambient temperature exposure during early pregnancy and crown-rump length (CRL).
Methods:
Data from the Generation R Next Study (2017-2021) were analysed, with findings replicated in the Generation R Study (2002-2006), both population-based cohorts based in Rotterdam, The Netherlands. Weekly mean temperatures were modeled from the last menstrual period onward at a spatial resolution of 100 × 100 m by using the UrbClim™ model. The CRL was measured via 2D ultrasound at approximately 8, 10, and 12 weeks' gestation in pregnancies with regular menstrual cycles. Distributed lag nonlinear models were applied.
Results:
In Generation R Next (N = 1378; mean maternal age 31.9 years), higher temperatures during the first 9 weeks were associated with a smaller CRL at 12 weeks {e.g. -7.2 mm [95% confidence interval (CI) -12.0, -2.3] at 19.2 vs 9.0°C during weeks 1-6}. Colder exposures during the first 11 weeks were also associated with a smaller CRL [-7.6 mm (95% CI -11.9, -3.3) at 3.6 vs 9.0°C during weeks 1-11]. No associations were observed for CRL at 8 or 10 weeks. Similar associations with cold, but not heat, were observed in the replication cohort (N = 1520).
Conclusion:
Moderate cold and heat exposure during early pregnancy may affect fetal development as early as the first trimester. These findings indicate that early gestational development may be sensitive to ambient temperature and, as environmental conditions shift, may have potential clinical implications for birth outcomes and long-term health.
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