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Risk of placental dysfunction disorders after prior miscarriages: a population-based study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
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2014 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 211, no 1, 34.e1-34.e8 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The objective of the investigation was to study the association between prior miscarriages and the risks of placental dysfunction disorders, including preeclampsia, stillbirth, birth of a small for gestational age (SGA) infant, placental abruption, and spontaneous preterm birth. STUDY DESIGN: In a population-based cohort study including 619,587 primiparous women, we estimated risks of placental dysfunction disorders for women with 1 (n = 68,185), 2 (n = 11,410) and 3 or more (n = 3823) self-reported prior miscarriages. Risks were calculated as odds ratios by unconditional logistic regression analysis and adjustments were made for maternal age, early pregnancy body mass index, height, smoking habits, country of birth, years of formal education, in vitro fertilization, chronic hypertension, pregestational diabetes, hypothyroidism, systemic lupus erythematosis, fetal sex, and year of childbirth. RESULTS: Compared with women with no prior miscarriage, women with 1 prior miscarriage had almost no increased risks. Women with 2 prior miscarriages had increased risks of spontaneous preterm birth, preterm (<37 weeks) SGA infant, and placental abruption. The rates of all disorders were higher for women with 3 or more prior miscarriages compared with women without prior miscarriages: preeclampsia, 5.83% vs 4.27%; stillbirth, 0.69% vs 0.33%, SGA infant, 5.09% vs 3.22%, placental abruption, 0.81% vs 0.41%; and spontaneous preterm birth, 6.45% vs 4.40%. The adjusted odds ratios for preterm (<37 weeks) disorders in women with 3 prior miscarriages were approximately 2. CONCLUSION: History of 2 or more miscarriages is associated with an increased risk of placental dysfunction disorders and should be regarded as a risk factor in antenatal care.

Place, publisher, year, edition, pages
2014. Vol. 211, no 1, 34.e1-34.e8 p.
Keyword [en]
intrauterine growth restriction, miscarriage, placental abruption, preeclampsia, spontaneous preterm birth, stillbirth
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-231320DOI: 10.1016/j.ajog.2014.01.041ISI: 000339747000013PubMedID: 24495667OAI: oai:DiVA.org:uu-231320DiVA: diva2:744270
Available from: 2014-09-08 Created: 2014-09-07 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Epidemiological Studies of Preeclampsia: Maternal & Offspring Perspectives 
Open this publication in new window or tab >>Epidemiological Studies of Preeclampsia: Maternal & Offspring Perspectives 
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Preeclampsia is a placental-related disorder characterized by generalized endothelial activation. Vascular predisposition is associated with the occurrence of preeclampsia and the recurrence risk is substantial. Onset of preeclampsia is preceded by placental hypo-perfusion, and placental over-production of vasoconstrictive agents might explain symptoms such as hypertension and proteinuria. Preeclampsia is associated with the birth of small-for-gestational-age (SGA) infants. The trajectory of postnatal growth in SGA-born children is described as catch-up, but it is unclear whether prenatal preeclampsia is independently associated with postnatal growth.

The objectives were: firstly, to study the association between partner change and prior miscarriages on the occurrence of preeclampsia and SGA; secondly, to study postnatal growth in children prenatally exposed to preeclampsia; and thirdly, to address the association between blood pressure (BP) changes during pregnancy and risks of preeclampsia and SGA.

Population-based cohort studies were performed with information from the following registers: Swedish Medical Birth Register, Uppsala Mother and Child Database and Stockholm-Gotland Obstetric Database. Associations were estimated with logistic and linear regression analyses, with adjustments for maternal characteristics, including body mass index, pre-gestational diseases and socioeconomic factors.

The results were, firstly, that partner change was associated with preeclampsia and SGA birth in the second pregnancy but depended on the outcome of the first pregnancy, and that a history of recurrent miscarriages was associated with increased risks of preeclampsia and SGA. Secondly, prenatal exposure to preeclampsia was associated with increased offspring growth in height during the first five years. This association was also seen in children born with normal birth weight for gestational age. Thirdly, pre-hypertension in late gestation and elevated diastolic BP from early to mid-gestation were both associated with SGA birth. Further, women with pre-hypertension in early gestation without lowered diastolic BP until mid-gestation seemed to represent a risk group for preeclampsia.

To conclude, the importance of previous pregnancy outcomes in the antenatal risk evaluation was highlighted. Secondly, the results imply that postnatal growth trajectory is related to maternal preeclampsia, in addition to SGA. Thirdly, the association between BP changes within a normal range and SGA may challenge the clinical cut-off for hypertension in pregnancy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1333
Keyword
Placental dysfunction, blood pressure, small-for-gestational-age, fetal growth restriction, intrauterine, prenatal exposure, postnatal height gain, linear growth
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-320138 (URN)978-91-554-9920-4 (ISBN)
Public defence
2017-06-09, Rosénsalen, Akademiska sjukhuset, Ingång 95/96 nbv, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2017-05-19 Created: 2017-04-21 Last updated: 2017-06-07

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Gunnarsdottir, JohannaWikström, Anna-Karin

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