A sister's risk: Family history as a predictor of preeclampsia

doi:10.1016/j.ajog.2005.06.034

American Journal of Obstetrics and Gynecology

Volume 193, Issue 3, Supplement, September 2005, Pages 965-972

https://doi.org/10.1016/j.ajog.2005.06.034 Get rights and content

Objective

The purpose of this study was to determine if women with preeclampsia are more likely to have a sister who also had preeclampsia.

Study design

This was a population-based case-control study using data from Washington (WA) state birth certificates linked to hospital discharge records. Cases were women with gestational hypertension (n = 1611) or preeclampsia (n = 1071); controls (n = 8041) had normotensive pregnancies. All women delivered their first child between 1987 to 2002 and had a sister with a previous delivery in WA.

Results

Women with preeclampsia were 2.3 times (95%CI 1.8-2.9) more likely to have a sister who had preeclampsia; those with gestational hypertension were 1.6 times (95%CI 1.3-2.0) more likely to have a sister with gestational hypertension. Similar results were obtained following stratification by age, race, smoking status, or body mass index.

Conclusion

The greater likelihood of preeclampsia among sisters of women with a previous preeclamptic pregnancy is consistent with a pathophysiologic role for genetic and/or behavioral factors that cluster in families.

Section snippets

Material and methods

A ‘Sisters’ database was constructed by linking birth certificates of girls born to the same mother in Washington state. A subset of sisters was then constructed from among sister pairs where each sister subsequently delivered at least 1 singleton infant in Washington state. The first 2 sisters in a family who delivered their first pregnancies between 1987 and 2002 were selected. For each sister pair, we designated the second sister to give birth as the ‘index sister’ and the sister who

Results

Among the index sisters, cases were generally similar to those of controls (Table I). Cases were more likely to be overweight or obese before conception, to have excessive weight gain during pregnancy, and to have gestational diabetes. Cases were less likely to smoke during pregnancy than controls. Among cases, women with preeclampsia/eclampsia were more likely to have pregestational diabetes than either women with gestational hypertension or controls, and more likely to have delivered <36

Comment

In our large study of sisters who delivered in Washington state, we demonstrated that primiparous women who did versus did not have preeclampsia/eclampsia had a higher risk of having a sister who also had preeclampsia. A similar relationship was found among women with gestational hypertension. Our findings suggest a pathophysiologic role for genetic factors in the development of preeclampsia as well as gestational hypertension. The potential importance of genetic factors in hypertensive

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Cited by (53)

Association of family history with incidence and gestational hypertension outcomes of preeclampsia
2021, International Journal of Cardiology: Hypertension
Citation Excerpt :
Preeclampsia, gestational hypertension, and other associated maternal diseases were identified using the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes (Supplemental Material Table 1), which were 642.4 (mild or unspecified preeclampsia), 642.5 (severe preeclampsia), 642.6 (eclampsia), 642.7 (preeclampsia/eclampsia with preexisting hypertension), 642.3 (gestational hypertension), 648.8 (gestational diabetes), 641.x (antepartum hemorrhage), and 666.x (postpartum hemorrhage). Preeclampsia has been defined in previous studies [15,16]. The Breslow–Cox proportional hazards model with a robust sandwich method was used to perform intra-familial clustering [17].
Gestational hypertension and preeclampsia are hypertensive disorders related to pregnancy that can cause maternal morbidity and fetal growth retardation. The association of these disorders with family history remains unclear.
To examine the degree of family aggregation of preeclampsia and gestational hypertension in Taiwan.
The study was conducted using the data from the National Health Insurance Database of Taiwan. Delivery events in Taiwan from 1999 to 2013 were collected. Preeclampsia was identified based on the hospital diagnosis of index delivery. The family aggregation pattern of preeclampsia was assessed and analyzed using the relationship registered in the database with the patients.
A total of 60,314 preeclampsia events were identified among 4,091,641 deliveries, accounting for 1.5% of the cohort. The incidence of preeclampsia increased with maternal age. A total of 768 preeclampsia events occurred in mothers who had a sororal history of preeclampsia (n = 20,704), accounting for 1.3% of all preeclampsia events (n = 60,314). Mothers who had a sororal history of preeclampsia had a relative risk (RR) of 2.6 (95% confidence interval [CI]: 2.41–2.80) for preeclampsia compared with mothers who did not have a sororal history of preeclampsia. The RR for gestational hypertension was 2.79 (95% CI: 2.36–3.3) in mothers with a positive sororal history of gestational hypertension.
Having a sororal history of preeclampsia was a strong risk factor for preeclampsia and gestational hypertension in mothers in Taiwan. The pattern of family aggregation was similar at all maternal ages.
Renal biomarkers of preeclampsia
2020, Kidney Biomarkers: Clinical Aspects and Laboratory Determination
Worldwide, preeclampsia and related-conditions are among the leading causes of maternal mortality, perinatal death, preterm birth, and low birth-weight. In the United States, the incidence of preeclampsia is increasing and may be related to the higher prevalence of hypertension, diabetes, obesity, delay in child-bearing, and the use of artificial reproductive technologies. Preeclampsia is usually defined as new-onset hypertension (i.e., SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg) and proteinuria (>0.3 g/day) arising after 20 weeks of gestation in a previously normotensive woman. In the absence of proteinuria, pre-eclampsia can be diagnosed as new-onset hypertension associated with thrombocytopenia, elevated liver transaminases, impaired renal function, pulmonary edema, new-onset visual or cerebral disturbances. During pregnancy, the oxidatively stressed placenta releases angiogenic and antiangiogenic factors into the maternal circulation, which cause the maternal systemic inflammatory response and endothelial dysfunction that lead to the clinical signs of preeclampsia. Some of these factors can be used as biomarkers for early screening and diagnosis of preeclempsia.
Preeclampsia: Disease biology and burden, its management strategies with reference to India
2019, Pregnancy Hypertension
Preeclampsia is the cause of significant maternal and fetal mortality and morbidity. It is characterized by new-onset hypertension and proteinuria after 20 weeks of gestation. Preeclamptic women and children born from preeclamptic pregnancies are at greater risk to develop severe cardiovascular complications and metabolic syndromes later in life. The incidence of preeclampsia is estimated to be seven times higher in developing countries as compared to the developed countries. This review summarizes the pathophysiology of preeclampsia, emerging new hypothesis of its origin, risk factors that make women susceptible to developing preeclampsia and the potential of various biomarkers being studied to predict preeclampsia. The health care of developing countries is continuously challenged by substantial burden of maternal and fetal mortality. India despite being a fast developing country, is still far behind in achieving the required maternal mortality rates as per Millennium Development Goals set by the World Health Organization. Further, this review discusses the prevalence of preeclampsia in India, health facilities to manage preeclampsia, current guidelines and protocols followed and government policies to combat this complication in Indian condition.
Preeclampsia: Pathogenesis, Prevention, and Long-Term Complications
2017, Seminars in Nephrology
Preeclampsia continues to afflict 5% to 8% of all pregnancies throughout the world and is associated with significant morbidity and mortality to the mother and the fetus. Although the pathogenesis of the disorder has not yet been fully elucidated, current evidence suggests that imbalance in angiogenic factors is responsible for the clinical manifestations of the disorder, and may explain why certain populations are risk. In this review, we begin by demonstrating the roles that angiogenic factors play in pathogenesis of preeclampsia and its complications in the mother and the fetus. We then continue to report on the use of angiogenic markers as biomarkers to predict and risk-stratify disease. Strategies to treat preeclampsia by correcting the angiogenic balance, either by promoting proangiogenic factors or by removing antiangiogenic factors in both animal and human studies, are discussed. We end the review by summarizing status of the current preventive strategies and the long-term cardiovascular outcomes of women afflicted with preeclampsia.
Fetal Val108/158Met catechol-O-methyltransferase (COMT) polymorphism and placental COMT activity are associated with the development of preeclampsia
2016, Fertility and Sterility
Citation Excerpt :
Finally, maternal homocysteine plasma levels were inversely correlated with 2-ME plasma levels (r = −0.223; P=.019 [n = 110] and B = −0.030; 95% CI −0.066 to 2.16 × 10−5; P=.05 [n = 107]) after adjustment for confounders (Fig. 1D). Although most cases of PE occur in the absence of familial history, the presence of this syndrome in a first-degree relative increases a woman's risk of severe PE two- to fourfold (23), suggesting a genetic contribution to the disease. On the other hand, different studies have confirmed the importance of a paternal factor, recalling that the placenta is a product of both parents (24, 25).
To evaluate the association between fetal and maternal catechol-O-methyltransferase (COMT) Val158Met and methyl tetrahydrofolate reductase (MTHFR) C677T functional polymorphisms and preeclampsia, examining its influence on placental COMT and in maternal 2-methoxyestradiol (2-ME) plasma levels.
Prospective case-control study.
University hospital.
A total of 53 preeclamptic and 72 normal pregnant women.
Maternal and cord blood samples and placental tissue samples were obtained.
Maternal and fetal COMT and MTHFR polymorphisms were genotyped. Maternal plasma 2-ME and homocysteine levels, and expression and activity of placental COMT were measured.
The odds ratio for the risk of preeclampsia for fetal COMT Met/Met was 3.22, and it increased to 8.65 when associated with fetal MTHFR TT. Placental COMT activity and expression were influenced by genotype, but COMT activity in preeclamptic placentas did not differ from control pregnancies. There was no association between any genotypes and maternal 2-ME. Homocysteine levels were higher in women with preeclampsia than in normal pregnancies, and were inversely correlated with 2-ME plasma levels, indicating that its altered metabolism may lower COMT activity in vivo.
Fetal Met-Met COMT genotype reduces COMT placental expression and activity in vitro and increases preeclampsia, risk but it does not explain the difference in maternal 2-ME levels between preeclamptic and normal pregnancies. However, the preeclamptic patients had elevated homocysteine levels that correlated inversely with 2-ME, indicating that an altered methionine-homocysteine metabolism may contribute to reduce COMT activity in vivo and explain the decreased levels of 2-ME in preeclamptic women.
Intraabdominal fat, insulin sensitivity, and cardiovascular risk factors in postpartum women with a history of preeclampsia
2015, American Journal of Obstetrics and Gynecology
Women who develop preeclampsia have a higher risk of future cardiovascular disease and diabetes compared to women who have uncomplicated pregnancies. We hypothesized that women with prior preeclampsia would have increased visceral adiposity that would be a major determinant of their metabolic and cardiovascular risk factors.
We compared intraabdominal fat (IAF) area, insulin sensitivity index (S_I), fasting lipids, low-density lipoprotein relative flotation rate, and brachial artery flow-mediated dilatation in 49 women with prior preeclampsia and 22 controls who were at least 8 months postpartum and matched for age, parity, body mass index, and months postpartum. Women were eligible if they did not smoke tobacco, use hormonal contraception, have chronic hypertension, or have a history of gestational diabetes.
The groups were similar for age (mean ± SD: prior preeclampsia 33.4 ± 6.6 vs control 34.6 ± 4.3 years), parity (median: 1 for both), body mass index (26.7 ± 5.9 vs 24.0 ± 7.3 kg/m²), and months postpartum (median [25th-75th percentile]: 16 [13-38] vs 16.5 [13-25]). There were no significant differences in IAF area and S_I. Despite this, women with preeclampsia had lower high-density lipoprotein (46.0 ± 10.7 vs 51.3 ± 9.3 mg/dL; P < .05), smaller/denser low-density lipoprotein relative flotation rate (0.276 ± 0.022 vs 0.289 ± 0.016; P = .02), higher systolic (114.6 ± 10.9 vs 102.3 ± 7.5 mm Hg) and diastolic (67.6 ± 7.5 vs 60.9 ± 3.6 mm Hg; P < .001) blood pressures, and impaired flow-mediated dilatation (4.5 [2-6.7] vs 8.8 [4.5-9.1] percent change, P < .05) compared to controls. In a subgroup analysis, women with nonsevere preeclampsia (n = 17) had increased IAF (98.3 [60.1-122.2]) vs 63.1 [40.1-70.7] cm²; P = .02) and decreased S_I (4.18 [2.43-5.25] vs 5.5 [3.9-8.3] × 10^-5 min^-1/pmol/L; P = .035) compared to the controls, whereas women with severe preeclampsia (n = 32) were not different for IAF and S_I. IAF was negatively associated with S_I and positively associated with cardiovascular risk factors even after adjusting for the matching variables and total body fat.
Women with prior preeclampsia have an atherogenic lipid profile and endothelial dysfunction compared to matched control subjects despite having similar adiposity and insulin sensitivity, suggesting that there are mechanisms separate from obesity and insulin resistance that lead to their cardiovascular risk factors. Visceral adiposity may have a role in contributing to these risk factors in the subgroup of women who have preeclampsia without severe features.

View all citing articles on Scopus

Drs Carr, Epplein, and Johnson contributed equally to this work.

Presented at the Twenty-Fifth Annual Meeting of the Society for Maternal Fetal Medicine, February 7-12, 2005, Reno, Nev.

Reprints not available from the authors.

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Transactions of the Twenty-Fifth Annual Meeting of the Society for Maternal-Fetal MedicineA sister's risk: Family history as a predictor of preeclampsia

Objective

Study design

Results

Conclusion

Section snippets

Material and methods

Results

Comment

Am J Obstet Gynecol

Am J Hum Genet

Am J Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Am J Kidney Dis

Lancet

Eur J Obstet Gynecol Reprod Biol

Am J Obstet Gynecol

Am J Obstet Gynecol

Hypertension in pregnancy

N Engl J Med

Summary of the NHLBI Working Group on Research on Hypertension During Pregnancy

Hypertens Pregnancy

Births and deaths: United States, July 1996-June 1997. National Center for Health Statistics. Births, marriages, divorces, and deaths for July 1997

Monthly Vital Statistics Report

A molecular variant of angiotensinogen associated with preeclampsia

Nat Genet

Implication of an AGT haplotype in a multigene association study with pregnancy hypertension

Hypertension

Transactions of the Twenty-Fifth Annual Meeting of the Society for Maternal-Fetal Medicine
A sister's risk: Family history as a predictor of preeclampsia