The association of maternal vaginal bleeding and progesterone supplementation in early pregnancy with offspring outcomes: a prospective cohort study

Chunrong Zhong, Guoping Xiong, Lixia Lin, Qian Li, Xi Chen, Xu Zhang, Yu Zhang, Shangzhi Xu, Xiaoyi Wang, Duan Gao, Meng Wu, Sen Yang, Weizhen Han, Guoqiang Sun, Xuefeng Yang, Liping Hao, Zhichun Jin, Nianhong Yang, Chunrong Zhong, Guoping Xiong, Lixia Lin, Qian Li, Xi Chen, Xu Zhang, Yu Zhang, Shangzhi Xu, Xiaoyi Wang, Duan Gao, Meng Wu, Sen Yang, Weizhen Han, Guoqiang Sun, Xuefeng Yang, Liping Hao, Zhichun Jin, Nianhong Yang

Abstract

Background: Progesterone is widely used to improve the adverse pregnancy outcomes related to vaginal bleeding during early pregnancy. However, the evidence of its effectiveness is equivocal.

Methods: Six thousand six hundred fifteen mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on vaginal bleeding, progesterone administration in early pregnancy were obtained at enrolment. Birth outcomes were obtained from the hospital notes. Body weight of the infants at 12 months of age was collected by telephone interview. Multivariable logistic regression was conducted to estimate the effect of vaginal bleeding and progesterone administration in early pregnancy on birth outcomes and weight status of infants at 12 months of age.

Results: 21.4% (1418/6615) participants experienced bleeding in early pregnancy, and 47.5% (674/1418) of them were treated with progesterone. There were no significant associations between progesterone supplementation in early pregnancy and offspring outcomes. Compared to women without bleeding or any therapy, women with bleeding and progesterone therapy experienced increased risk of preterm (OR 1.74, 95% CI 1.21-2.52), and delivering a small-for-gestational-age (SGA) (OR 1.46, 95% CI 1.07-1.98) or low birth weight (LBW) (OR 2.10, 95% CI 1.25-3.51) neonate, and offspring of them had an increased risk of weight for age z-score (WAZ) < -1 at 12 months of age (OR 1.79, 95%CI 1.01-3.19).

Conclusions: Offspring of mothers with bleeding and progesterone therapy were more likely to be a premature, SGA or LBW neonate, and had lower weight at 12 months of age. Progesterone supplementation may have no beneficial effect on improving adverse offspring outcomes related to early vaginal bleeding.

Trial registration: TMCHC was registered at clinicaltrials.gov as NCT03099837 on 4 April 2017.

Keywords: Low birth weight; Preterm; Progesterone; Small-for-gestational-age; Vaginal bleeding; Weight for age z-score.

Conflict of interest statement

The authors report no conflict of interest.

© 2022. The Author(s).

References

    1. Everett C. Incidence and outcome of bleeding before the 20th week of pregnancy: prospective study from general practice. BMJ. 1997;315(7099):32–34. doi: 10.1136/bmj.315.7099.32.
    1. Al-Memar M, Vaulet T, Fourie H, et al. Early-pregnancy events and subsequent antenatal, delivery and neonatal outcomes: prospective cohort study. Ultrasound Obstet Gynecol. 2019;54(4):530–537. doi: 10.1002/uog.20262.
    1. Sun L, Tao F, Hao J, Su P, Liu F, Xu R. First trimester vaginal bleeding and adverse pregnancy outcomes among Chinese women: from a large cohort study in China. J Matern Fetal Neonatal Med. 2012;25(8):1297–1301. doi: 10.3109/14767058.2011.632034.
    1. Yang J, Hartmann KE, Savitz DA, et al. Vaginal bleeding during pregnancy and preterm birth. Am J Epidemiol. 2004;160(2):118–125. doi: 10.1093/aje/kwh180.
    1. Yang J, Savitz DA. The effect of vaginal bleeding during pregnancy on preterm and small-for-gestational-age births: US National Maternal and Infant Health Survey, 1988. Paediatr Perinat Epidemiol. 2001;15(1):34–39. doi: 10.1046/j.1365-3016.2001.00318.x.
    1. Williams MA, Mittendorf R, Lieberman E, Monson RR. Adverse infant outcomes associated with first-trimester vaginal bleeding. Obstet Gynecol. 1991;78(1):14–18.
    1. Strobino B, Pantel-Silverman J. Gestational vaginal bleeding and pregnancy outcome. Am J Epidemiol. 1989;129(4):806–815. doi: 10.1093/oxfordjournals.aje.a115195.
    1. Bever AM, Pugh SJ, Kim S, et al. Fetal Growth Patterns in Pregnancies With First-Trimester Bleeding. Obstet Gynecol. 2018;131(6):1021–1030. doi: 10.1097/AOG.0000000000002616.
    1. Malassine A, Frendo JL, Evain-Brion D. A comparison of placental development and endocrine functions between the human and mouse model. Hum Reprod Update. 2003;9(6):531–539. doi: 10.1093/humupd/dmg043.
    1. Robinson DP, Klein SL. Pregnancy and pregnancy-associated hormones alter immune responses and disease pathogenesis. Horm Behav. 2012;62(3):263–271. doi: 10.1016/j.yhbeh.2012.02.023.
    1. Romero R, Conde-Agudelo A, Da Fonseca E, et al. Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix: a meta-analysis of individual patient data. Am J Obstet Gynecol. 2018;218(2):161–180. doi: 10.1016/j.ajog.2017.11.576.
    1. Dodd JM, Jones L, Flenady V, Cincotta R, Crowther CA. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database Syst Rev. 2013;7:Cd004947.
    1. Jarde A, Lutsiv O, Beyene J, McDonald SD. Vaginal progesterone, oral progesterone, 17-OHPC, cerclage, and pessary for preventing preterm birth in at-risk singleton pregnancies: an updated systematic review and network meta-analysis. BJOG. 2019;126(5):556–567. doi: 10.1111/1471-0528.15566.
    1. Norman JE, Marlow N, Messow CM, et al. Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial. Lancet (London, England) 2016;387(10033):2106–2116. doi: 10.1016/S0140-6736(16)00350-0.
    1. Coomarasamy A, Williams H, Truchanowicz E, et al. A Randomized Trial of Progesterone in Women with Recurrent Miscarriages. N Engl J Med. 2015;373(22):2141–2148. doi: 10.1056/NEJMoa1504927.
    1. Coomarasamy A, Devall AJ, Cheed V, et al. A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. N Engl J Med. 2019;380(19):1815–1824. doi: 10.1056/NEJMoa1813730.
    1. Norman JE, Marlow N, Messow CM, et al. Does progesterone prophylaxis to prevent preterm labour improve outcome? A randomised double-blind placebo-controlled trial (OPPTIMUM) Health Technol Assess. 2018;22(35):1–304. doi: 10.3310/hta22350.
    1. Zhou B. Predictive values of body mass index and waist circumference to risk factors of related diseases in Chinese adult population. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi. 2002;23(1):5–10.
    1. Zhu L, Zhang R, Zhang S, et al. Chinese neonatal birth weight curve for different gestational age. Zhonghua er ke za zhi = Chinese journal of pediatrics. 2015;53(2):97–103.
    1. WHO Multicentre Growth Reference Study Group . WHO Child Growth Standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. Geneva: World Health Organization; 2006.

Source: PubMed

3
Abonner