A prospective cohort study providing insights for markers of adverse pregnancy outcome in older mothers

Abstract Background Advanced maternal age (≥35 years) is associated with increased rates of adverse pregnancy outcome. Better understanding of underlying pathophysiological processes may improve identification of older mothers who are at greatest risk. This study aimed to investigate changes in oxidative stress and inflammation in older women and identify clinical and biochemical predictors of adverse pregnancy outcome in older women. Methods The Manchester Advanced Maternal Age Study (MAMAS) was a multicentre, observational, prospective cohort study of 528 mothers. Participants were divided into three age groups for comparison 20–30 years (n = 154), 35–39 years (n = 222) and ≥ 40 years (n = 152). Demographic and medical data were collected along with maternal blood samples at 28 and 36 weeks’ gestation. Multivariable analysis was conducted to identify variables associated with adverse outcome, defined as one or more of: small for gestational age (< 10th centile), FGR (<5th centile), stillbirth, NICU admission, preterm birth < 37 weeks’ gestation or Apgar score < 7 at 5 min. Biomarkers of inflammation, oxidative stress and placental dysfunction were quantified in maternal serum. Univariate and multivariable logistic regression was used to identify associations with adverse fetal outcome. Results Maternal smoking was associated with adverse outcome irrespective of maternal age (Adjusted Odds Ratio (AOR) 4.22, 95% Confidence Interval (95%CI) 1.83, 9.75), whereas multiparity reduced the odds (AOR 0.54, 95% CI 0.33, 0.89). In uncomplicated pregnancies in older women, lower circulating anti-inflammatory IL-10, IL-RA and increased antioxidant capacity (TAC) were seen. In older mothers with adverse outcome, TAC and oxidative stress markers were increased and levels of maternal circulating placental hormones (hPL, PlGF and sFlt-1) were reduced (p < 0.05). However, these biomarkers only had modest predictive accuracy, with the largest area under the receiver operator characteristic (AUROC) of 0.74 for placental growth factor followed by TAC (AUROC = 0.69). Conclusions This study identified alterations in circulating inflammatory and oxidative stress markers in older women with adverse outcome providing preliminary evidence of mechanistic links. Further, larger studies are required to determine if these markers can be developed into a predictive model of an individual older woman’s risk of adverse pregnancy outcome, enabling a reduction in stillbirth rates whilst minimising unnecessary intervention.

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A Prospective Cohort Study providing Insights for Markers of Adverse Pregnancy Outcome in Women of Advanced Maternal Age

10.21203/rs.3.rs-130070/v1 ◽

2020 ◽

Author(s):

Samantha Lean ◽

Rebecca Jones ◽

Stephen Roberts ◽

Alexander Heazell

Keyword(s):

Oxidative Stress ◽

Pregnancy Outcome ◽

Maternal Age ◽

Adverse Outcome ◽

Adverse Pregnancy Outcome ◽

Advanced Maternal Age ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Adverse Pregnancy ◽

And Oxidative Stress

Abstract Background Advanced maternal age (AMA; ≥35 years) is associated with increased rates of adverse pregnancy outcome. Better understanding of underlying pathophysiological processes may improve identification of AMA mothers who are at greatest risk of adverse outcome. This study aimed to investigate changes in oxidative stress and inflammation in AMA women and identify clinical and biochemical predictors of adverse pregnancy outcome in women of AMA.Methods The Manchester Advanced Maternal Age Study (MAMAS) was a multicentre, observational, prospective cohort study of 527 mothers. Participants were divided into three age groups for comparison 20-30 years (n=158), 35-39 years (n=212) and ≥40 years (n=157). Demographic and medical data were collected along with maternal blood samples at 28 and 36 weeks’ gestation. Multivariable analysis was conducted to identify variables associated with adverse outcome, defined as one or more of: small for gestational age (<10th centile), FGR (<5th centile), stillbirth, NICU admission, preterm birth <37 weeks gestation or Apgar score <7 at 5 minutes. Biomarkers of inflammation, oxidative stress and placental dysfunction were quantified in maternal serum. Univariate and multivariable statistical analyses were used to identify associations with composite adverse fetal outcome.Results: Maternal smoking was associated with adverse outcome in older mothers (Adjusted Odds Ratio (AOR) 4.34, 95% Confidence Interval (95%CI) 1.88, 9.99), whereas multiparity reduced the odds (AOR 0.56, 95% CI 0.34, 0.99). In uncomplicated AMA pregnancies, lower circulating anti-inflammatory IL-10, IL-RA and increased antioxidant capacity (TAC) were seen. In AMA with adverse outcome, TAC and oxidative stress markers were increased and levels of maternal circulating placental hormones (hPL, PlGF and sFlt-1) were reduced (p<0.05). Of these, placental growth factor had the strongest predictive accuracy (Area Under the Receiver Operator Characteristic (AUROC) = 0.74) followed by TAC (AUROC=0.69).Conclusions: This study identified alterations in circulating inflammatory and oxidative stress markers in AMA women and in AMA women with adverse pregnancy outcome providing preliminary evidence of mechanistic links. Further, larger studies are required to determine if these markers can be developed into a predictive model of an individual AMA woman’s risk of APO, enabling a reduction in stillbirth rates whilst minimising unnecessary intervention.

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Association between adverse pregnancy outcome and imbalance in angiogenic regulators and oxidative stress biomarkers in gestational hypertension and preeclampsia

BMC Pregnancy and Childbirth ◽

10.1186/s12884-015-0624-y ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 48

Author(s):

Cornelius A. Turpin ◽

Samuel A. Sakyi ◽

William KBA Owiredu ◽

Richard KD. Ephraim ◽

Enoch O. Anto

Keyword(s):

Oxidative Stress ◽

Pregnancy Outcome ◽

Gestational Hypertension ◽

Adverse Pregnancy Outcome ◽

Oxidative Stress Biomarkers ◽

Stress Biomarkers ◽

Adverse Pregnancy ◽

And Oxidative Stress

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Abstract 11: Improved Prediction of Adverse Pregnancy Outcome With the sFlt-1/PlGF Ratio in Patients Suspected of Preeclampsia?

Hypertension ◽

10.1161/hyp.62.suppl_1.a11 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Koen Verdonk ◽

Manon van Ingen ◽

Johanna E Smilde ◽

Eric A Steegers ◽

A. H. Jan Danser ◽

...

Keyword(s):

Pregnancy Outcome ◽

Gestational Age ◽

Predictive Value ◽

Odds Ratio ◽

Adverse Outcome ◽

Adverse Pregnancy Outcome ◽

Positive Test ◽

Positive Ratio ◽

Adverse Pregnancy ◽

Plgf Ratio

The sFlt-1/PlGF ratio has high sensitivity and specificity to diagnose preeclampsia (PE) and to predict pregnancy outcome. Especially in patients with preexisting hypertension and/or proteinuria, diagnosis and management of PE is challenging. We studied the predictive value of the sFlt-1/PlGF ratio for the occurrence of adverse outcome in patients with a high prevalence of preexisting hypertension or proteinuria, clinically suspected of having PE. A sFlt-1/PlGF ratio >= 85 was considered to be a positive test. Adverse pregnancy outcome was defined as HELPP syndrome, intra-uterine growth restriction, or perinatal death. The predictive value of adverse pregnancy outcome of preeclampsia based on clinical grounds (clinical PE) or of a positive ratio was compared using a logistic regression model corrected for gestational age at testing. Results: So far 64 patients with a gestational age (GA) of 29.3 wks (range 20-37 wks) were included. 19 had preexisting hypertension, 5 had preexisting proteinuria and 6 had both conditions. At time of measurement 23 patients had clinical PE (4 with a negative ratio) and 30 patients had a positive sFlt-1/PlGF test (11 without clinical PE at testing of whom 7 developed clinical PE within 2 wks). 27% of patients had an adverse outcome of pregnancy. GA between patients with clinical PE or a positive test did not differ. Patients with clinical PE at the time of testing had an odds ratio of 2.5 (95% CI: 0.75 - 7.8) and patients with a positive test had an odds ratio of 6.8 (95% CI;2.1 - 33.9) for an adverse outcome. Patients with clinical PE had an absolute risk for an adverse outcome of 39% (9/23) compared to 46%(14/30) for patients with a positive sFlt-1/PlGF test (p=.075) In patients where the diagnosis of PE is challenging because of preexisting hypertension and/or proteinuria a positive sFlt-1/PlGF is a stronger determinant for poor pregnancy outcome than the clinical diagnosis of PE. An explanation could be that a positive ratio can select patients that will develop PE in the near future and because of misclassification of patients with preexisting hypertension and/or proteinuria.

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Fetal origin of adverse pregnancy outcome: The water disinfectant by-product chloroacetonitrile induces oxidative stress and apoptosis in mouse fetal brain

Developmental Brain Research ◽

10.1016/j.devbrainres.2005.05.008 ◽

2005 ◽

Vol 159 (1) ◽

pp. 1-11 ◽

Cited By ~ 19

Author(s):

Ahmed E. Ahmed ◽

Sam Jacob ◽

Gerald A. Campbell ◽

Hassan M. Harirah ◽

J. Regino Perez-Polo ◽

...

Keyword(s):

Oxidative Stress ◽

Pregnancy Outcome ◽

Adverse Pregnancy Outcome ◽

Fetal Brain ◽

Fetal Origin ◽

Adverse Pregnancy

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Advanced Maternal Age and Adverse Pregnancy Outcome: Evidence from a Large Contemporary Cohort

PLoS ONE ◽

10.1371/journal.pone.0056583 ◽

2013 ◽

Vol 8 (2) ◽

pp. e56583 ◽

Cited By ~ 232

Author(s):

Louise C. Kenny ◽

Tina Lavender ◽

Roseanne McNamee ◽

Sinéad M. O’Neill ◽

Tracey Mills ◽

...

Keyword(s):

Pregnancy Outcome ◽

Maternal Age ◽

Adverse Pregnancy Outcome ◽

Advanced Maternal Age ◽

Adverse Pregnancy

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Maternal age and adverse pregnancy outcome: a cohort study

Ultrasound in Obstetrics and Gynecology ◽

10.1002/uog.12494 ◽

2013 ◽

Vol 42 (6) ◽

pp. 634-643 ◽

Cited By ~ 144

Author(s):

A. Khalil ◽

A. Syngelaki ◽

N. Maiz ◽

Y. Zinevich ◽

K. H. Nicolaides

Keyword(s):

Cohort Study ◽

Pregnancy Outcome ◽

Maternal Age ◽

Adverse Pregnancy Outcome ◽

Adverse Pregnancy

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Lipotoxicity in obese pregnancy and its potential role in adverse pregnancy outcome and obesity in the offspring

Clinical Science ◽

10.1042/cs20090640 ◽

2010 ◽

Vol 119 (3) ◽

pp. 123-129 ◽

Cited By ~ 131

Author(s):

Eleanor Jarvie ◽

Sylvie Hauguel-de-Mouzon ◽

Scott M. Nelson ◽

Naveed Sattar ◽

Patrick M. Catalano ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Fatty Acids ◽

Endothelial Dysfunction ◽

Maternal Obesity ◽

Adverse Pregnancy Outcome ◽

Oxidized Lipids ◽

Lower Body ◽

Adverse Pregnancy ◽

And Oxidative Stress

Increasing maternal obesity is a challenge that has an impact on all aspects of female reproduction. Lean and obese pregnant women gain similar fat mass, but lean women store fat in the lower-body compartment and obese women in central compartments. In the non-pregnant, central storage of fat is associated with adipocyte hypertrophy and represents a failure to adequately store excess fatty acids, resulting in metabolic dysregulation and ectopic fat accumulation (lipotoxicity). Obese pregnancy is associated with exaggerated metabolic adaptation, endothelial dysfunction and increased risk of adverse pregnancy outcome. We hypothesize that the preferential storage of fat in central rather than ‘safer’ lower-body depots in obese pregnancy leads to lipotoxicity. The combination of excess fatty acids and oxidative stress leads to the production of oxidized lipids, which can be cytotoxic and influence gene expression by acting as ligands for nuclear receptors. Lipid excess and oxidative stress provoke endothelial dysfunction. Oxidized lipids can inhibit trophoblast invasion and influence placental development, lipid metabolism and transport and can also affect fetal developmental pathways. As lipotoxicity has the capability of influencing both maternal endothelial function and placental function, it may link maternal obesity and placentally related adverse pregnancy outcomes such as miscarriage and pre-eclampsia. The combination of excess/altered lipid nutrient supply, suboptimal in utero metabolic environment and alterations in placental gene expression, inflammation and metabolism may also induce obesity in the offspring.

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Childbearing after age 35: its effect on early perinatal outcomes

Journal of Biosocial Science ◽

10.1017/s0021932000013870 ◽

1982 ◽

Vol 14 (1) ◽

pp. 69-80 ◽

Cited By ~ 1

Author(s):

Judith A. Fortney ◽

J. E. Higgins ◽

A. Diaz-Infante ◽

F. Hefnawi ◽

L. G. Lampe ◽

...

Keyword(s):

Older Women ◽

Pregnancy Outcome ◽

Adverse Pregnancy Outcome ◽

Perinatal Outcomes ◽

Good Health ◽

Social Risk ◽

Social Risk Factors ◽

Developed Country ◽

Age Related ◽

Adverse Pregnancy

SummaryBirths to women aged 35 years and older are compared with births to women aged 20–34 in three hospitals, one each in Mexico, Egypt and Hungary. In the two developing countries, babies born to the older women had lower rates of survival until hospital discharge, and were more likely to have depressed 5-minute Apgar scores. They were not, however, more likely to be of low birth weight. The differences were statistically significant, and remained when several other variables were controlled. The variables controlled were known to be age-related and to influence pregnancy outcome.Hungary, the only developed country in the analysis, was quite different. Age had a significant influence on the weight of the infant, but not on survival or Apgar score. It seems therefore that when older women are in general good health and there are no concurrent social risk factors, advanced maternal age does not necessarily increase the risk of an adverse pregnancy outcome.

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