Maternal prepregnancy obesity is associated with higher risk of placental pathological lesions

doi:10.1016/j.placenta.2014.05.006

Placenta

Volume 35, Issue 8, August 2014, Pages 563-569

https://doi.org/10.1016/j.placenta.2014.05.006 Get rights and content

Highlights

•
Maternal prepregnancy obesity was associated with higher risk of placenta pathological lesions.
•
The OR of vascular atheroma in decidua in obese women was the highest (OR 1.97, 95% CI 1.11-3.50).
•
Placenta-to-birthweight ratio increased with maternal prepregnancy BMI.

Abstract

Introduction

Prepregnancy obesity is associated with increased morbidity and mortality for mother and offspring. The objective of our study is to estimate the effect of maternal prepregnancy weight on placental pathological lesions..

Methods

Data used for this study were from the U.S. Collaborative Perinatal Project, a large prospective cohort study. It consisted of 54390 women giving a singleton birth from 1959 to 1966. More than 84% of women had both detailed placental pathological examinations and anthropometric measurements. Logistic regression models were used to test the associations between maternal prepregnancy body mass index (BMI) and placental pathological lesions adjusting for potential confounders. Spline smoothing was applied to describe the relation of prepregnancy BMI and placenta weight-to-birthweight ratio.

Results

The prepregnancy obese women (BMI ≥ 30 kg/m²) showed a higher rate of maternal origin vascular lesions, maternal origin villous lesions, fetal neutrophilic infiltration, and meconium of fetal membrane compared with the normal-weight women (18.5 ≤ BMI < 24.9). The odds ratios ranged from 1.18 to 1.97 after adjusting for potential confounders. These higher odds were consistent in prepregnancy obese women without obstetric complications. Furthermore, placenta weight-to-birthweight ratio, the proxy for placenta insufficiency, was positively associated with maternal prepregnancy BMI..

Conclusions

Our study provides evidence that prepregnancy obesity exerts its adverse in-utero influence on placental pathology. These influences may have impact on maternal and fetal health. With obesity rising steadily, these results appear to raise serious public health concerns of prepregnancy obesity.

Introduction

In 2005 the World Health Organization declared obesity a “worldwide pandemic” affecting 400 million adults [1]. In the United States (U.S.), more than one third of women of child bearing ages are obese and more than one half are overweight or obese, which presents a major health problem [2]. Studies have shown that prepregnancy obesity is associated with higher prevalence of morbidity and mortality for mothers and offspring, including gestational diabetes mellitus, pre-eclampsia, late stillbirth, large-for-gestational age, and offspring's long-term consequences of obesity and metabolic syndrome [3], [4]. Systematically altered insulin secretion and elevated maternal cholesterol level in obese women may result in increased expression of inflammatory cytokines IL-1, IL-6 and TNF-a [5]. It has been proposed that this pro-inflammatory maternal and fetal environment may play a role in mediating adverse pregnancy outcomes for both mother and fetus [6], [7]. However, because pathologic examination results were typically not available in most studies, the evidence of the link between maternal obesity and placental pathological lesions are scarce. To the best of our knowledge, only one study compared placental histopathology findings between obese women and normal-weight pregnant women with or without the confounding of maternal complications [8]. With relatively small sample size (<100), this study showed the association of obesity and inflammation of the placenta, but failed to find the association with maternal or fetal vascular lesions.

Obstetric complications were supposed to be an important partial pathway in the association of maternal obesity and adverse perinatal outcome in some studies [9]. Whether prepregnancy obesity has an effect on placental pathology in women without obstetric complications remains unclear. The aim of the present study is to examine the effect of maternal prepregnancy body mass index (BMI) on the placenta pathological lesions in the Collaborative Perinatal Project (CPP) in the U.S.

Section snippets

Study population

The CPP was a prospective cohort study that recruited 46,021 women with 54,390 singleton pregnancies who received prenatal care at 12 centers in the U.S. from 1959 to 1966. Eighteen percent of the participants had more than one birth in the CPP. The average gestational age at entry was 21.3 ± 8.4 (mean ± standard deviation) weeks of gestation. At entry, detailed demographic, socioeconomic and behavioral information was collected by in-person interview. At the ensuing prenatal visits women were

Results

The sample selection process was illustrated in Fig. 1. In 54,390 singleton births, 84.2% (n = 45,785) women have placental pathology reports. After exclusion of subjects without anthropometric measurement, 39,774 women remained for the final analysis.

Most of maternal and child characteristics varied significantly by maternal prepregnancy BMI status except for marital status, child gender, placenta previa, and placenta abruption (Table 1). Blacks had a higher percentage of overweight and obese

Discussion

The association between obesity and perinatal adverse outcomes is well established in the literature [22]. The placenta is in a key position to mediate environmental effects because adequate placental function is necessary for delivery of nutrients, oxygen, and hormones to the fetus. However, the effect of maternal obesity on placenta pathological lesions remains unclear. Our study explored the potential contribution of placental pathological lesions in obese women. Among the placental

Conclusion

Prevalence of obesity is increasing in many parts of countries in the world. Our data suggests that maternal prepregnancy obesity is associated with an increased risk of placental insufficiency, vascular and villous lesions of maternal origins, fetal neutrophilic infiltration, meconium of fetal membranes, and immaturity of the placenta. This study provides evidence that prepregnancy obesity had an in-utero influence on offspring leading to a cycling of risk factors through generations.

Contributors

Lisu Huang, Jun Zhang and Weiye Wang designed the study. Lisu Huang did the statistical analyses. Lisu Huang wrote the first draft. All authors contributed to the design and interpretation of the study, critically revised the manuscript, and approved the final version.

Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 81273091), and Shanghai Municipal Health Bureau (GWIII-26.2).

Competing interests

The authors have no interests to declare.

Ethical approval

IRB approval process is not required for research 50 years ago. All of the patient information was anonymized and de-identified prior to analysis.

Data sharing

No additional data available.

Acknowledgments

We are grateful to the U.S. National Archives and Records Administration for providing data of the Collaborative Perinatal Project.

References (42)

K.A. Roberts et al.
Placental structure and inflammation in pregnancies associated with obesity
Placenta
(2011)
J.B. Hardy
The collaborative perinatal project: lessons and legacy
Ann Epidemiol
(2003)
A. Ghidini et al.
Placental vascular lesions and likelihood of diagnosis of preeclampsia
Obstet Gynecol
(1997)
R.W. Redline et al.
Placental diagnostic criteria and clinical correlation–a workshop report
Placenta
(2005)
N.C. Myrianthopoulos et al.
An application of the U.S. Bureau of the Census socioeconomic index to a large, diversified patient population
Soc Sci Med
(1968)
G.A. Wood et al.
On the use of spline functions for data smoothing
J Biomech
(1979)
L. Higgins et al.
Obesity and the placenta: a consideration of nutrient exchange mechanisms in relation to aberrant fetal growth
Placenta
(2011)
J.C. Madan et al.
Maternal obesity and markers of inflammation in pregnancy
Cytokine
(2009)
R.H. Eckel et al.
The metabolic syndrome
Lancet
(2005)
R.C. Fretts
Etiology and prevention of stillbirth
Am J Obstet Gynecol
(2005)

O. Stephansson et al.

Maternal weight, pregnancy weight gain, and the risk of antepartum stillbirth

Am J Obstet Gynecol

(2001)

E. Villamor et al.

Interpregnancy weight change and risk of adverse pregnancy outcomes: a population-based study

Lancet

(2006)

S.Y. Chu et al.

Maternal obesity and risk of stillbirth: a metaanalysis

Am J Obstet Gynecol

(2007)

D.J. Barker et al.

Fetal nutrition and cardiovascular disease in adult life

Lancet

(1993)

A.T. Tita et al.

Diagnosis and management of clinical chorioamnionitis

Clin Perinatol

(2010)

A.D. Gernand et al.

Maternal serum 25-hydroxyvitamin D and placental vascular pathology in a multicenter US cohort

Am J Clin Nutr

(2013)

World Health Organisation

Obesity and overweight

(2006)

K.M. Flegal et al.

Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010

JAMA

(2012)

C.M. Boney et al.

Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus

Pediatrics

(2005)

E.A. Nohr et al.

Prepregnancy obesity and fetal death: a study within the Danish National Birth Cohort

Obstet Gynecol

(2005)

D.R. Grattan

Fetal programming from maternal obesity: eating too much for two?

Endocrinology

(2008)

Cited by (74)

Placental pathologic features in obesity
2023, Placenta
Obesity in pregnancy is associated with adverse long-term consequences both in the mother and in offspring. Maternal obesity induces a metabolic-inflammatory state that could impact on placental function and could mediate the adverse outcomes. The purpose of this study was to compare the major placental histological characteristics of non-diabetic obese women to lean controls, focusing on uncomplicated pregnancies.
Prospective case-control study comparing placental histopathological features between 122 non-diabetic obese women and 185 non-obese controls. The analysis was performed on overall subjects, then uncomplicated pregnancies from both groups were analyzed. Placenta pathologic findings were recorded according to standard classification.
Both in overall analysis and among the subset of subjects with an uncomplicated pregnancy, obese subjects had higher risks of maternal vascular malperfusion (MVM) (respectively OR=2.2, 95%CI =1.3–3.7 and OR=4.2, 95%CI=2.1–8.5), fetal vascular malperfusion (FVM) (respectively OR=6.3, 95%CI=3.1–12.5 and OR=7.2, 95%CI=3–17.2), maternal and fetal inflammatory response placental lesions and villitis (VUE) (respectively OR=2.5, 95%CI=1.1–5.6 and OR=10.8, 95%CI=3.3–35.3) compared to controls. Among uncomplicated pregnancies and after adjustment for confounders, first trimester BMI was significantly associated with overall MVM, overall FVM, maternal inflammatory, fetal inflammatory response and VUE.
Placentas from obese women showed a significantly higher risk of maternal and fetal vascular and inflammatory placental lesions, both in overall population and in the subgroup with uncomplicated pregnancies. The metabolic and inflammatory dysfunctions typical of obesity could have an impact on placental development and function, which could be a mediator of the detrimental effects of obesity on pregnancy outcome and on future health of the offspring.
Prepregnancy obesity and risk of placental inflammation at term: a selection bias analysis
2023, Annals of Epidemiology
Placental histopathology is a resource for investigating obesity-associated pregnancy conditions. However, studies oversample adverse pregnancies, biasing findings. We examine the association between prepregnancy obesity (risk factor for inflammation) and histologic placental inflammation (correlated with impaired infant neurodevelopment) and how selection bias may influence the association.
Singleton term deliveries between 2008 and 2012 from the Magee Obstetric Maternal and Infant database were analyzed. Prepregnancy body mass index (BMI) was categorized as underweight, lean (referent), overweight, and obese. Outcomes were diagnoses of acute (acute chorioamnionitis and fetal inflammation) and chronic placental inflammation (chronic villitis). Risk ratios for associations between BMI and placental inflammation were estimated using selection bias approaches: complete case, exclusion of pregnancy complications, multiple imputation, and inverse probability weighting. E-values approximated how susceptible estimates were to residual selection bias.
Across methods, obesity was associated with an 8–15% lower risk of acute chorioamnionitis, a 7%–14% lower risk of acute fetal inflammation, and a 12%–30% higher risk of chronic villitis relative to lean women. E-values indicated modest residual selection bias could explain away associations, though few measured indications of placental evaluations met this threshold.
Obesity may contribute to placental inflammation, and we highlight robust methods to analyze clinical data susceptible to selection bias.
High early pregnancy body mass index is associated with alterations in first- and second-trimester angiogenic biomarkers
2022, American Journal of Obstetrics and Gynecology MFM
Obesity is associated with various placenta-mediated adverse pregnancy outcomes, including preeclampsia, preterm birth, and stillbirth. Mechanisms linking obesity with placental dysfunction are not completely understood.
This study aimed to examine the relationship between early pregnancy body mass index and placental angiogenic biomarkers soluble fms-like tyrosine kinase-1, placental growth factor, and the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio.
We conducted secondary analyses of an existing substudy within a multisite, prospective observational cohort study of nulliparous pregnant women in the United States. First- and second-trimester maternal blood samples, first-trimester body mass index, and demographic, lifestyle, and pregnancy outcomes data were collected. Soluble fms-like tyrosine kinase-1 and placental growth factor concentrations were measured at 6 to 13 and 16 to 22 weeks of gestation for women (cases) who experienced one of several adverse pregnancy outcomes (delivery at <37 weeks of gestation, preeclampsia or eclampsia, birthweight for gestational age <5th percentile, or stillbirth) and for those who had none of those outcomes (controls). We used multivariable mixed-effects linear regression models to estimate the association of body mass index with angiogenic biomarkers at both time points. We evaluated mean change between first- and second-trimester biomarker concentrations using multivariable linear regression models. Lastly, we used logistic regression models to estimate the risk of a high second-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratio, using clinically established cutoffs for risk prediction.
Angiogenic biomarker and early pregnancy body mass index data were available for 2363 women (1467 with adverse pregnancy outcomes and 896 controls). High early pregnancy body mass index was associated with consistently lower soluble fms-like tyrosine kinase-1 concentrations across the first and second trimesters of pregnancy. We found lower first-trimester placental growth factor concentrations in the group with class II or III obesity (P<.001) and lower second-trimester placental growth factor concentrations among groups who were overweight, with class I obesity, and class II or III obesity (P<.001). For every unit increase in early pregnancy body mass index, there was a −4.4 pg/mL (95% confidence interval, −3.6 to −5.2) smaller mean increase in placental growth factor concentrations between the first and second trimesters of pregnancy. These differences resulted in significantly lower mean first-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratios among groups who were overweight, with class I obesity, and class II or III obesity (P<.05) and in a significantly higher second-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratio among the group with class II or III obesity (P<.001), compared with the group with normal body mass index. Each unit of increase in body mass index was associated with a 0.5 (95% confidence interval, 0.3–0.7) greater mean increase in the soluble fms-like tyrosine kinase-1–to–placental growth factor ratio between the first and second trimesters of pregnancy. In stratified analyses, associations between body mass index and angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were similar in nonadverse pregnancy outcome and adverse pregnancy outcome subgroups, whereas associations between body mass index and the soluble fms-like tyrosine kinase-1–to–placental growth factor ratio were attenuated in the subgroups. Participants in the group with class II or III obesity were 3.13 (95% confidence interval, 1.15–8.49) times more likely than participants with normal weight to have a second-trimester ratio of ≥38 in univariate analysis.
High early pregnancy body mass index was associated with lower soluble fms-like tyrosine kinase-1 and placental growth factor concentrations across early pregnancy. Maternal body mass was inversely associated with first-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratios and positively associated with second-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratios, driven by a diminished rise in placental growth factor between the first and second trimesters of pregnancy. Women with class II or III obesity have an increased risk of a high second-trimester soluble fms-like tyrosine kinase-1–to–placental growth factor ratio associated with placental dysfunction.
Maternal Immune Activation Hypotheses for Human Neurodevelopment: Some Outstanding Questions
2022, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
The maternal immune activation hypothesis is a leading model for understanding prenatal influences on individual differences in, and clinical syndromes of, neurodevelopment. Experimental animal and human research has proliferated in recent years, and there is now a sizable research base. Several meta-analyses demonstrate general support for an association between prenatal immune activation and neurodevelopment in human research. However, questions remain about the nature of the immune activation, network of underlying mechanisms involved, and breadth of impact across behavioral phenotypes. Complementing recent reviews of results, the current review places particular emphasis on how a better understanding of mechanisms may be achieved with greater attention to addressing the methodological variation and limitations of existing studies and identifies areas for further clinical research.
Placental Findings in Pregnancies Complicated by Maternal Cardiovascular Disease
2022, JACC: Advances
The incidence of pregnancy in women with cardiovascular disease (CVD) has increased, yet little is known about placental pathology in these women.
The objectives of this study were to describe placental pathology in pregnancies complicated by maternal CVD and to compare findings among categories of maternal CVD.
A retrospective, single-center study was conducted. Pathology reports for 264 placentas from pregnancies complicated by maternal CVD were reviewed for prespecified pathologic findings which were then compared against maternal characteristics.
Placentas were from pregnancies associated with maternal congenital heart disease (n = 171), arrhythmia (n = 43), cardiomyopathy (n = 20), connective tissue disease (n = 20), and valvular heart disease (n = 10). Median maternal age at delivery was 32 years (range: 19-49). Median gestational age at delivery was 39 weeks (range: 25-41). Placental pathology was identified in 75% (199/264) of placentas. Anatomic pathology, primarily small placenta by weight, was present in 45% (119/264) of placentas. Vascular pathology, primarily maternal vascular malperfusion or fetal vascular malperfusion, was seen in 41% (107/264) of placentas. Acute chorioamnionitis and villitis of unknown etiology (VUE) were seen in 23% (61/264) and 11% (28/264) of placentas, respectively. Prevalence of VUE differed across CVD categories (P = 0.008) and was most common in maternal congenital heart disease; there were no differences in anatomic, infectious, and vascular pathologies across CVD categories.
Pregnancies among women with CVD commonly demonstrate abnormal placental findings, especially anatomic and vascular pathology. Prevalence of VUE differed across CVD categories. Otherwise, the incidence of specific pathology findings did not differ based on maternal characteristics.
Placental pathology
2022, Reproductive and Developmental Toxicology

View all citing articles on Scopus

View full text

Maternal prepregnancy obesity is associated with higher risk of placental pathological lesions

Highlights

Abstract

Introduction

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Conclusion

Contributors

Funding

Competing interests

Ethical approval

Data sharing

Acknowledgments

Placenta

Ann Epidemiol

Obstet Gynecol

Placenta

Soc Sci Med

J Biomech

Placenta

Cytokine

Lancet

Am J Obstet Gynecol

Am J Obstet Gynecol

Lancet

Am J Obstet Gynecol

Lancet

Clin Perinatol

Am J Clin Nutr

Obesity and overweight

Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010

JAMA

Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus

Pediatrics

Prepregnancy obesity and fetal death: a study within the Danish National Birth Cohort

Obstet Gynecol

Fetal programming from maternal obesity: eating too much for two?

Endocrinology