Endometriosis linked to elevated risk of placenta previa in pregnancy

Association between surgically diagnosed endometriosis and adverse pregnancy outcomes

2018 Study Abstract

Objective
To examine the association between surgically diagnosed endometriosis and pregnancy outcomes in subsequent pregnancies.

Design
Retrospective cohort study of women who delivered a singleton live birth from 2003 to 2013 in Ottawa, Ontario, Canada.

Setting
Tertiary level academic center.

Patient(s)
Pregnant women with surgically diagnosed endometriosis were identified using International Classification of Diseases-10 codes from previous hospital admissions and were compared with pregnant women with no prior admission for endometriosis for the occurrences of adverse pregnancy outcomes.

Intervention(s)
Observational study.

Main Outcome Measure(s)
Gestational hypertension, preeclampsia, placenta previa, placental abruption, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and neonatal intensive care unit admission.

Results
Among the 52,202 eligible mother-infant pairs, we identified 469 mothers with surgically diagnosed endometriosis from a previous hospital encounter. Compared with women without endometriosis, women with endometriosis were on average older and were more likely to be primiparous, have lower gravidity, have a history spontaneous abortion, conceive with assisted reproductive technology, and reside in areas with higher neighborhood income and lower proportion of immigrants. Women with endometriosis were found to have an elevated risk of placenta previa (relative risk [RR], 3.30; 95% confidence interval [CI], 1.65–5.40) and cesarean delivery (RR, 1.24; 95% CI, 1.10–1.40). After adjustment for potential confounding factors, women with endometriosis were found to have a significantly elevated risk of placenta previa compared with women without endometriosis (adjusted RR, 2.54; 95% CI, 1.39–4.64).

Conclusion(s)
This study identifies baseline demographic differences between women with and without endometriosis and suggests that women affected by endometriosis have an independently elevated risk of placenta previa in pregnancy.

Can in vitro fertilisation increase the risk for preeclampsia ?

Embryo cryopreservation and preeclampsia risk

Pre-eclampsia is a disorder of pregnancy that increases the risk of poor outcomes for both the mother and the baby.

2017 Study Abstract

Objective
To determine whether assisted reproductive technology (ART) cycles involving cryopreserved-warmed embryos are associated with the development of preeclampsia.

Design
Retrospective cohort study.

Setting
IVF clinics and hospitals.

Patient(s)
A total of 15,937 births from ART: 9,417 singleton and 6,520 twin.

Intervention(s)
We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data, considering resident singleton and twin births from autologous or donor eggs from 2005–2010.

Main Outcome Measure(s)
We compared the frequency of preeclampsia diagnosis for cryopreserved-warmed versus fresh ET and used multivariable logistic regression to adjust for confounders.

Result(s)
Among pregnancies conceived with autologous eggs resulting in singletons, preeclampsia was greater after cryopreserved-warmed versus fresh ET (7.51% vs. 4.29%, adjusted odds ratio = 2.17 [95% CI 1.67–2.82]). Preeclampsia without and with severe features, preeclampsia with preterm delivery, and chronic hypertension with superimposed preeclampsia were more frequent after cryopreserved-warmed versus fresh ET (3.99% vs. 2.55%; 2.95% vs. 1.41%; 2.76 vs. 1.48%; and 0.95% vs. 0.43%, respectively). Among pregnancies from autologous eggs resulting in twins, the frequency of preeclampsia with severe features (9.26% vs. 5.70%) and preeclampsia with preterm delivery (14.81% vs. 11.74%) was higher after cryopreserved versus fresh transfers. Among donor egg pregnancies, rates of preeclampsia did not differ significantly between cryopreserved-warmed and fresh ET (10.78% vs. 12.13% for singletons and 28.0% vs. 25.15% for twins).

Conclusion(s)
Among ART pregnancies conceived using autologous eggs resulting in live births, those involving transfer of cryopreserved-warmed embryos, as compared with fresh ETs, had increased risk for preeclampsia with severe features and preeclampsia with preterm delivery.

Sources

Pregnancy complications in patients with endometriosis

Prenatal exposure to estrogenic substances (such as DES) and environmental toxins (such as bisphenols) may increase the incidence of endometriosis in female offspring

Zullo et al. have done an extensive and thorough meta-analysis of the literature concerning endometriosis and pregnancy complications, one of the largest and most comprehensive studies to date.

Their systematic review and meta-analysis : endometriosis and obstetrics complications, provides further insight into endometriosis and pregnancy by combining the many heterogeneous studies on this topic, and it raises awareness of the many implications of endometriosis.

2017 Study Abstract

Objective
To evaluate the effect of endometriosis on pregnancy outcomes.

Design
Systematic review and meta-analysis.

Setting
Not applicable.

Patient(s)
Women with or without endometriosis.

Intervention(s)
Electronic databases searched from their inception until February 2017 with no limit for language and with all cohort studies reporting the incidence of obstetric complications in women with a diagnosis of endometriosis compared with a control group (women without a diagnosis of endometriosis) included.

Main Outcome Measure(s)
Primary outcome of incidence of preterm birth at <37 weeks with meta-analysis performed using the random effects model of DerSimonian and Laird to produce an odds ratio (OR) with 95% confidence interval (CI).

Result(s)
Twenty-four studies were analyzed comprising 1,924,114 women. In most of them, the diagnosis of endometriosis was made histologically after surgery. Women with endometriosis had a statistically significantly higher risk of preterm birth (OR 1.63; 95% CI, 1.32-2.01), miscarriage (OR 1.75; 95% CI, 1.29-2.37), placenta previa (OR 3.03; 95% CI, 1.50-6.13), small for gestational age (OR 1.27; 95% CI, 1.03-1.57), and cesarean delivery (OR 1.57; 95% CI, 1.39-1.78) compared with the healthy controls. No differences were found in the incidence of gestational hypertension and preeclampsia.

Conclusion(s)
Women with endometriosis have a statistically significantly higher risk of preterm birth, miscarriage, placenta previa, small for gestational age infants, and cesarean delivery.

EDCs exposure linked to altered gene function in pregnant women’s placentas

Chemicals may alter placenta genes, threaten fetuses

image of a Spritz-of-Perfume
Researchers link endocrine disrupting chemical exposure to altered gene function in pregnant women’s placentas, which could hamper fetal growth. A Spritz of Perfume image by Jennuine Captures Photography.

Women exposed to widely used chemicals while pregnant are more likely to have altered gene function in their placentas, according to a new study.

2015 Study Abstract

Background:
There is increasing concern that early-life exposure to endocrine-disrupting chemicals (EDCs) can influence the risk of disease development. Phthalates and phenols are two classes of suspected EDCs that are used in a variety of everyday consumer products, including plastics, epoxy resins, and cosmetics. In utero exposure to EDCs may impact disease propensity through epigenetic mechanisms.

Objective:
The objective of this study was to determine if prenatal exposure to multiple EDCs is associated with changes in miRNA expression of human placenta, and if miRNA alterations are associated with birth outcomes.

Methods:
Our study was restricted to a total of 179 women co-enrolled in the Harvard Epigenetic Birth Cohort and the Predictors of Preeclampsia Study. We analyzed associations between first-trimester urine concentrations of 8 phenols and 11 phthalate metabolites and expression of 29 candidate miRNAs in placenta by qRT-PCR.

Results:
For three miRNAs, miR-142-3p, miR15a-5p, and miR-185, we detected associations between ∑phthalates or ∑phenols on expression levels (p<0.05). By assessing gene ontology enrichment, we determined the potential mRNA targets of these microRNAs predicted in silico were associated with several biological pathways, including the regulation of protein serine/threonine kinase activity. Four gene ontology biological processes were enriched among genes significantly correlated with the expression of miRNAs associated with EDC burden.

Conclusions:
Overall, these results suggest that prenatal phenol and phthalate exposure is associated with altered miRNA expression in placenta, suggesting a potential mechanism of EDC toxicity in humans.

Sources and more information
  • First-Trimester Urine Concentrations of Phthalate Metabolites and Phenols and Placenta miRNA Expression in a Cohort of U.S. Women, Environ Health Perspect; DOI:10.1289/ehp.1408409, 19 June 2015.
  • Chemicals may alter placenta genes, threaten fetuses, Environmental Health News, July 1, 2015.

Preeclampsia Risk in Women exposed in Utero to DiEthylStilbestrol

In utero exposure to DES is associated with a 50 % higher risk of preeclampsia

DES Follow-up Study Summary

National Cancer Inst logo image
In utero exposure to DES is associated with a 50 % higher risk of preeclampsia.

Women exposed to Diethylstilbestrol (DES) in utero experience a greater risk of adverse reproductive events including infertility, ectopic pregnancies, spontaneous pregnancy losses and premature births. These complications may in part be due to prenatal effects of DES on the structure of the uterus or cervix. Preeclampsia, a common pregnancy complication characterized by maternal hypertension, and high levels of uric acid and protein, frequently involves the placenta not entirely attaching to the mother’s endometrium (implantation). DES-associated uterine abnormalities and possible alterations in immune function may adversely affect successful implantation.

The hypothesis that prenatal DES exposure is associated with preeclampsia risk was previously addressed in a small case-control study that reported a greater than two-fold risk in women who reported a history of DES exposure compared with those who did not. We used data from the National Cancer Institute DES Combined Cohorts Follow-up Study to readdress this issue. A total of 285 preeclampsia cases (210 exposed and 75 unexposed) occurred in 7313 live births (4759 DES exposed and 2554 unexposed). Prenatal DES exposure was associated with nearly a 50% elevation in preeclampsia risk in the daughters’ pregnancies. Taking into account differences in DES exposed and unexposed women in preeclampsia risk factors including age at the pregnancy, number of pregnancies, education, smoking, a measure of body fatness, and year of preeclampsia diagnosis, the risk was slightly lower, about 40%. The increased risk of preeclampsia associated with prenatal DES exposure was concentrated among women who developed preeclampsia in their first pregnancy (80% higher risk), those who were exposed to DES before 15 weeks of pregnancy (57% higher risk) and those who were treated with magnesium sulfate (over two times the risk). Among DES-exposed women who had a prior hysterosalpingogram (a procedure that allows physicians to view the reproductive organs), preeclampsia prevalence was higher in those with uterine abnormalities (12.4%) than in those without (7.7%). Our data suggest that prenatal DES exposure is associated with a slightly elevated risk of preeclampsia that is possibly due to a higher prevalence of uterine abnormalities in DES daughters.

Women exposed to diethylstilbestrol (DES) in utero experience a greater risk of adverse reproductive events including infertility, ectopic gestations, spontaneous pregnancy losses and premature births. These complications may in part be mediated through teratogenic effects, namely the structural uterine and cervical abnormalities that have been associated with in utero DES exposure. Preeclampsia, a common pregnancy complication characterized by maternal hypertension, hyperuricemia, and proteinuria frequently involves shallow placentation. Placental establishment requires cytotrophoblast invasion of the underlying stroma and blood vessels of the maternal endometrium, a process involving immune and angiogenic mechanisms. DES-associated uterine abnormalities and possible alterations in immune function (4-7) may adversely affect successful implantation.

The hypothesis that prenatal DES exposure is associated with preeclampsia risk was previously addressed in a small case-control study that reported a greater than two-fold risk in women who reported a history of DES exposure compared with those who did not.

2007 Study Abstract

Objective:
To assess whether preeclampsia risk is elevated in pregnancies of diethylstilbestrol (DES)-exposed daughters.

Methods:
This study used data from the National Cancer Institute DES Combined Cohorts Follow-up Study. A total of 285 preeclampsia cases (210 exposed and 75 unexposed) occurred in 7,313 live births (4,759 DES exposed and 2,554 unexposed). Poisson regression analysis estimated relative risks and 95% confidence intervals (CI) for preeclampsia adjusted for age at the index pregnancy, parity, education, smoking, body mass index, year of diagnosis, and cohort.

Result:
In utero DES exposure was associated with nearly a 50% elevation in preeclampsia risk. Adjustment for preeclampsia risk factors attenuated the relative risk slightly (1.42, 95% CI 1.04-1.94). The excess risk with DES was concentrated among women who developed preeclampsia in their first pregnancies (relative risk 1.81, 95% CI 1.17-2.79), who were exposed before 15 weeks of gestation (relative risk 1.57, 95% CI 1.11-2.23), and who were treated with magnesium sulfate (relative risk 2.10, 95% CI 0.82-5.42). Among DES-exposed women who had a prior hysterosalpingogram, preeclampsia prevalence was higher in those with uterine abnormalities (12.4%) than in those without (7.7%).

Conclusion:
These data suggest that in utero exposure to DES is associated with a slightly elevated risk of preeclampsia, and that one possible biological mechanism involves uterine abnormalities.

Sources

  • Preeclampsia risk in women exposed in utero to diethylstilbestrol,NCBI, PMID: 17601905, 2007 Jul;110(1):113-20.
  • NCI, DES Follow-up Study Published Papers.
More DES DiEthylStilbestrol Resources

Adverse Health Outcomes in Women exposed in Utero to DiEthylStilbestrol

In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes

2011 Study Abstract:

Adverse health outcomes in women exposed in utero to diethylstilbestrol
High lifetime risk of a broad spectrum of adverse health outcomes in the DES Daughters

BACKGROUND:
Before 1971, several million women were exposed in utero to Diethylstilbestrol (DES) given to their mothers to prevent pregnancy complications. Several adverse outcomes have been linked to such exposure, but their cumulative effects are not well understood.

METHODS:
We combined data from three studies initiated in the 1970s with continued long-term follow-up of 4653 women exposed in utero to DES and 1927 unexposed controls. We assessed the risks of 12 adverse outcomes linked to DES exposure, including cumulative risks to 45 years of age for reproductive outcomes and to 55 years of age for other outcomes, and their relationships to the baseline presence or absence of vaginal epithelial changes, which are correlated with a higher dose of, and earlier exposure to, DES in utero.

RESULTS:
Cumulative risks in women exposed to DES, as compared with those not exposed, were as follows:

  • for infertility, 33.3% vs. 15.5% (hazard ratio, 2.37; 95% confidence interval [CI], 2.05 to 2.75)
  • spontaneous abortion, 50.3% vs. 38.6% (hazard ratio, 1.64; 95% CI, 1.42 to 1.88)
  • preterm delivery, 53.3% vs. 17.8% (hazard ratio, 4.68; 95% CI, 3.74 to 5.86)
  • loss of second-trimester pregnancy, 16.4% vs. 1.7% (hazard ratio, 3.77; 95% CI, 2.56 to 5.54)
  • ectopic pregnancy, 14.6% vs. 2.9% (hazard ratio, 3.72; 95% CI, 2.58 to 5.38)
  • preeclampsia, 26.4% vs. 13.7% (hazard ratio 1.42; 95% CI, 1.07 to 1.89)
  • stillbirth, 8.9% vs. 2.6% (hazard ratio, 2.45; 95% CI, 1.33 to 4.54)
  • early menopause, 5.1% vs. 1.7% (hazard ratio, 2.35; 95% CI, 1.67 to 3.31)
  • grade 2 or higher cervical intraepithelial neoplasia, 6.9% vs. 3.4% (hazard ratio, 2.28; 95% CI, 1.59 to 3.27)
  • breast cancer at 40 years of age or older, 3.9% vs. 2.2% (hazard ratio, 1.82; 95% CI, 1.04 to 3.18).

For most outcomes, the risks among exposed women were higher for those with vaginal epithelial changes than for those without such changes.

CONCLUSIONS:
In utero exposure of women to DES is associated with a high lifetime risk of a broad spectrum of adverse health outcomes. (Funded by the National Cancer Institute).

Sources:

More DES DiEthylStilbestrol Resources