Sex-specific effect of first-trimester maternal progesterone on birthweight

STUDY QUESTION: Are maternal progesterone levels in early pregnancy associated with fetal birthweight? SUMMARY ANSWER: Low levels of first-trimester maternal progesterone are significantly associated with a reduction in birthweight in girls, but not boys. WHAT IS ALREADY KNOWN: Progesterone in the third trimester of pregnancy has previously been related to birthweight in humans. STUDY DESIGN, SIZE, DURATION: Pregnant women between gestational weeks 4 and 12 were recruited by 99 obstetricians in private practice and enrolled in a prospective cohort study. A follow-up took place at birth. Women younger than 18 years, who had undergone fertility treatments or were diagnosed with infectious diseases, were excluded from the study. A subgroup of 906 participants in whom progesterone had been measured was then selected retrospectively based on the following criteria: no miscarriages, elective abortions or pregnancy complications, infections or multiple births. Data from the follow-up were available for 623 women, who were included in the analyses. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was coordinated at the Charite University Medicine in Berlin, Germany. Anthropometric, medical and psychosocial information were collected and serum progesterone and estradiol levels were measured in women during the first trimester of pregnancy, followed by the documentation of the pregnancy outcome at birth. Univariable and multivariable regression analyses were performed to identify maternal markers, among them progesterone, affecting birthweight and to determine environmental and maternal factors that are associated with maternal progesterone levels during pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In the multivariable regression model, each increase in maternal progesterone by 1 ng/ml during the first trimester increased girls' birthweight by 10.17 g (95% CI: 2.03-18.31 g). If themother carried a boy, maternal smoking and perceived worries during early pregnancy predicted a reduced birthweight, irrespective of progesterone levels. Maternal body mass index over 25 and maternal age,21 years significantly correlated with the reduced levels of progesterone. Correlations between environmental challenges and maternal progesterone did not reach levels of significance. Since the analyses were exploratory, the likelihood that results may be due to chance is increased. LIMITATIONS, REASONS FOR CAUTION: Due to the exploratory nature of the analyses, results need to be independently confirmed in a larger sample. Furthermore, our findings pertain to pregnant women without pregnancy complications or fertility treatments. WIDER IMPLICATIONS OF THE FINDINGS: Maternal progesterone during early pregnancy is an indicator of subsequent fetal development in female children. Future studies should confirm this relationship and determine whether maternal progesterone is a useful tool in predicting pregnancies at risk resulting in the birth of a girl with low birthweight. Detailed identification of environmental factors modulating maternal progesterone levels should be addressed in future studies.