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Epidemiological Studies of Preeclampsia: Maternal & Offspring Perspectives 
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
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. , p. 69
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1333
Keywords [en]
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: urn:nbn:se:uu:diva-320138ISBN: 978-91-554-9920-4 (print)OAI: oai:DiVA.org:uu-320138DiVA, id: diva2:1089892
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
List of papers
1. The paternal role in pre-eclampsia and giving birth to a small for gestational age infant: a population-based cohort study
Open this publication in new window or tab >>The paternal role in pre-eclampsia and giving birth to a small for gestational age infant: a population-based cohort study
2012 (English)In: BMJ open, ISSN 2044-6055, Vol. 2, no 4, p. e001178-Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

To estimate the effect of partner change on risks of pre-eclampsia and giving birth to a small for gestational age infant.

DESIGN:

Prospective population study.

SETTING:

Sweden.

PARTICIPANTS:

Women with their first and second successive singleton births in Sweden between 1990 and 2006 without pregestational diabetes and/or hypertension (n=446 459).

OUTCOME MEASURES:

Preterm (<37 weeks) and term (≥37 weeks) pre-eclampsia, and giving birth to a small for gestational age (SGA) infant. Risks were adjusted for interpregnancy interval, maternal age, body mass index, height and smoking habits in second pregnancy, years of involuntary childlessness before second pregnancy, mother's country of birth, years of formal education and year of birth. Further, when we calculated risks of SGA we restricted the study population to women with non-pre-eclamptic pregnancies.

RESULTS:

In women who had a preterm pre-eclampsia in first pregnancy, partner change was associated with a strong protective effect for preterm pre-eclampsia recurrence (OR 0.24; 95% CI 0.07 to 0.88). Similarly, partner change was also associated with a protective effect of recurrence of SGA birth (OR 0.75; 95% CI 0.67 to 0.84). In contrast, among women without SGA in first birth, partner change was associated with an increased risk of SGA in second pregnancy. Risks of term pre-eclampsia were not affected by partner change.

CONCLUSIONS:

There is a paternal effect on risks of preterm pre-eclampsia and giving birth to an SGA infant.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-186861 (URN)10.1136/bmjopen-2012-001178 (DOI)000315049300065 ()22936817 (PubMedID)
Available from: 2012-11-29 Created: 2012-11-29 Last updated: 2017-04-21Bibliographically approved
2. Risk of placental dysfunction disorders after prior miscarriages: a population-based study
Open this publication in new window or tab >>Risk of placental dysfunction disorders after prior miscarriages: a population-based study
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2014 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 211, no 1, p. 34.e1-34.e8Article 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.

Keywords
intrauterine growth restriction, miscarriage, placental abruption, preeclampsia, spontaneous preterm birth, stillbirth
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-231320 (URN)10.1016/j.ajog.2014.01.041 (DOI)000339747000013 ()24495667 (PubMedID)
Available from: 2014-09-08 Created: 2014-09-07 Last updated: 2018-01-24Bibliographically approved
3. Prenatal exposure to preeclampsia is associated with accelerated height gain in early childhood
Open this publication in new window or tab >>Prenatal exposure to preeclampsia is associated with accelerated height gain in early childhood
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(English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203Article in journal (Refereed) Submitted
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-320671 (URN)
Available from: 2017-04-23 Created: 2017-04-23 Last updated: 2017-11-29
4. Prehypertension in Pregnancy and Risks of Small for Gestational Age Infant and Stillbirth
Open this publication in new window or tab >>Prehypertension in Pregnancy and Risks of Small for Gestational Age Infant and Stillbirth
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2016 (English)In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 67, no 3, p. 640-646Article in journal (Refereed) Published
Abstract [en]

It is not fully known whether maternal prehypertension is associated with increased risk of adverse fetal outcomes, and it is debated whether increases in blood pressure during pregnancy influence adverse fetal outcomes. We performed a population-based cohort study in nonhypertensive women with term (37 weeks) singleton births (n=157446). Using normotensive (diastolic blood pressure [DBP] <80 mmHg) women as reference, we calculated adjusted odds ratios with 95% confidence intervals between prehypertension (DBP 80-89 mmHg) at 36 gestational weeks (late pregnancy) and risks of a small-for-gestational-age (SGA) birth or stillbirth. We further estimated whether an increase in DBP from early to late pregnancy affected these risks. We found that 11% of the study population had prehypertension in late pregnancy. Prehypertension was associated with increased risks of both SGA birth and stillbirth; adjusted odds ratios (95% confidence intervals) were 1.69 (1.51-1.90) and 1.70 (1.16-2.49), respectively. Risks of SGA birth in term pregnancy increased by 2.0% (95% confidence intervals 1.5-2.8) per each mmHg rise in DBP from early to late pregnancy, whereas risk of stillbirth was not affected by rise in DBP during pregnancy. We conclude that prehypertension in late pregnancy is associated with increased risks of SGA birth and stillbirth. Risk of SGA birth was also affected by rise in DBT during pregnancy. Our findings provide new insight to the relationship between maternal blood pressure and fetal well-being and suggest that impaired maternal perfusion of the placenta contribute to SGA birth and stillbirth.

Keywords
blood pressure, fetal death, fetal growth retardation, prehypertension, stillbirth
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-280233 (URN)10.1161/HYPERTENSIONAHA.115.06752 (DOI)000369755200028 ()26831196 (PubMedID)
Funder
Swedish Research Council, 2014-3561
Available from: 2016-03-09 Created: 2016-03-09 Last updated: 2018-01-24Bibliographically approved
5. Elevated diastolic blood pressure until mid-gestation is associated with preeclampsia and small for gestational age.
Open this publication in new window or tab >>Elevated diastolic blood pressure until mid-gestation is associated with preeclampsia and small for gestational age.
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-320672 (URN)
Available from: 2017-04-23 Created: 2017-04-23 Last updated: 2017-05-03

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