Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

Background Advanced maternal age (AMA; ≥35 years) is an increasing trend and is reported to be associated with various pregnancy complications. Objective To determine the risk of stillbirth and other adverse pregnancy outcomes in women of AMA. Search strategy Embase, Medline (Ovid), Cochrane Database of Systematic Reviews, ClinicalTrials.gov, LILACS and conference proceedings were searched from ≥2000. Selection criteria Cohort and case-control studies reporting data on one or more co-primary outcomes (stillbirth or fetal growth restriction (FGR)) and/or secondary outcomes in mothers ≥35 years and <35 years. Data collection and analysis The effect of age on pregnancy outcome was investigated by random effects meta-analysis and meta-regression. Stillbirth rates were correlated to rates of maternal diabetes, obesity, hypertension and use of assisted reproductive therapies (ART). Main results Out of 1940 identified titles; 63 cohort studies and 12 case-control studies were included in the meta-analysis. AMA increased the risk of stillbirth (OR 1.75, 95%CI 1.62 to 1.89) with a population attributable risk of 4.7%. Similar trends were seen for risks of FGR, neonatal death, NICU unit admission restriction and GDM. The relationship between AMA and stillbirth was not related to maternal morbidity or ART. Conclusions Stillbirth risk increases with increasing maternal age. This is not wholly explained by maternal co-morbidities and use of ART. We propose that placental dysfunction may mediate adverse pregnancy outcome in AMA. Further prospective studies are needed to directly test this hypothesis.

/pdf/advanced-maternal-age-and-adverse-pregnancy-outcomes-a-56wl9w29pq.pdf

Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis.

Earlier studies have reported the effectiveness of aspirin in preventing preeclampsia in women considered to be at moderate to high risk of developing this disorder. This current study was a meta-analysis of cohort studies examining risk factors for preeclampsia with the goal of estimating early in pregnancy (r16wk gestation) a woman’s risk of developing preeclampsia based on the presence of absence of various risk factors. Three practical estimates were generated: the absolute risk of developing preeclampsia in the presence or absence of a given risk factor; the relative risk in the presence or absence of a given risk factor, and the population attributable fraction (PAF) for preeclampsia in relation to each risk factor. On the basis of their analysis, the authors aimed to provide a list of risk factors that could be used to identify those women at high risk for developing preeclampsia. The PubMed and Embase databases were used to identify articles studying the association between preeclampsia and one or more risk factors in a previous pregnancy or in the current pregnancy. They specifically evaluated practical risk factors that were patient specific, easily remembered by the patient or found in previous medical records, and could be determined in the first trimester by the physician. Risk factors studied included: previous history of preeclampsia, placental abruption, intrauterine growth restriction (IUGR), or stillbirth; nulliparity; advanced maternal age; chronic hypertension; preexisting diabetes; high body mass index (BMI); kidney disease; lupus; antiphospholipid (aPL) antibody syndrome; multiple gestation, and assisted reproduction. The pooled preeclampsia event rate in the exposed and unexposed groups was calculated for each risk factor and pooled relative risk was calculated. Subsequently the PAF for each risk factor was calculated using the pooled relative risks. A total of 25,356,688 pregnancies from 92 studies were included in the meta-analysis. The mean pooled event rate for preeclampsia among all risk factors was 2.7% (SD=0.93%) for unexposed groups, while the mean pooled event rate for all exposed groups was 7.3% (SD= 4.6%). The highest pooled rate of preeclampsia was observed in women with aPL antibody syndrome [17.3%, 95% confidence Interval (CI), 6.8%-31.4%] while a previous history of preeclampsia had the highest pooled relative risk (8.4; 95% CI, 7.1-9.9). Chronic hypertension was the risk factor with the second highest pooled rate (16.0%; 95% CI, 12.6%-19.7%) and pooled relative risk (5.1%; 95% CI, 4.0%-6.5%) for preeclampsia. Preexisting diabetes, BMI >30, and pregnancy achieved by assisted reproduction were other risk factors with notably high pooled rates and relative risks. The presence of all but one of the risk factors evaluated (IUGR) was determined to significantly increase the risk of developing preeclampsia. Although aPL antibody syndrome was associated with the highest rate of preeclampsia it is a relatively uncommon disorder and therefore had one of the lowest PAFs for preeclampsia (0.18%; 95% CI, 0.08%-0.33%), whereas nulliparity, prepregnancy BMI >25, and prior preeclampsia were found to have the highest PAFs (32.3%; 95% CI, 27.4%-37.0%; 23.8%; 95% CI, 22.0%-25.6%; and 22.8%; 95% CI, 19.6%-26.3%, respectively). On the basis of their meta-analysis, the investigators identified multiple risk factors that could be used to identify early in pregnancy women who are at “high risk” of developing preeclampsia. They suggest this information could be used to develop a clinical prediction model that would be useful in determining those women who would benefit from aspirin prophylaxis during their pregnancies.

/pdf/clinical-risk-factors-for-preeclampsia-determined-in-early-seyf5wieqa.pdf

Clinical Risk Factors for Preeclampsia Determined in Early Pregnancy: Systematic Review and Meta-Analysis of Large Cohort Studies

Over the last decade, there has been a significant increase in average paternal age when the first child is conceived, either due to increased life expectancy, widespread use of contraception, late marriages and other factors. While the effect of maternal ageing on fertilization and reproduction is well known and several studies have shown that women over 35 years have a higher risk of infertility, pregnancy complications, spontaneous abortion, congenital anomalies, and perinatal complications. The effect of paternal age on semen quality and reproductive function is controversial for several reasons. First, there is no universal definition for advanced paternal ageing. Secondly, the literature is full of studies with conflicting results, especially for the most common parameters tested. Advancing paternal age also has been associated with increased risk of genetic disease. Our exhaustive literature review has demonstrated negative effects on sperm quality and testicular functions with increasing paternal age. Epigenetics changes, DNA mutations along with chromosomal aneuploidies have been associated with increasing paternal age. In addition to increased risk of male infertility, paternal age has also been demonstrated to impact reproductive and fertility outcomes including a decrease in IVF/ICSI success rate and increasing rate of preterm birth. Increasing paternal age has shown to increase the incidence of different types of disorders like autism, schizophrenia, bipolar disorders, and childhood leukemia in the progeny. It is thereby essential to educate the infertile couples on the disturbing links between increased paternal age and rising disorders in their offspring, to better counsel them during their reproductive years.

https://link.springer.com/content/pdf/10.1186%2Fs12958-015-0028-x.pdf

Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring

Male infertility is a widespread condition among couples. In about 50% of cases, couple infertility is attributable to the male partner, mainly due to a failure in spermatogenesis. In recent times, the crucial role that modifiable lifestyle factors play in the development of infertility have generated a growing interest in this field of study, i.e. aging, psychological stress, nutrition, physical activity, caffeine, high scrotal temperature, hot water, mobile telephone use. Several studies have investigated associations between semen quality and the presence of lifestyle stressors i.e. occupational, life events (war, earthquake, etc.) or couple infertility; overall, these studies provide evidence that semen quality is impaired by psychological stress. In this review, we will discuss the impact of quality of life (modifiable lifestyle factors) and psychological stress on male fertility. In addition, the role that increased scrotal temperature along with inappropriate nutritional and physical exercise attitudes exert on male fertility will be presented. The decline of male fertility, particularly associated with advancing age, incorrect lifestyles and environmental factors plays an important role on natality, and its consequences on the future on human population makes this an important public health issue in this century. Thus, modification of lifestyle through a structured program of educational, environmental, nutritional/physical exercise and psychological support, combined with the use of nutraceutical antioxidants can prevent infertility and therefore, may help couples to obtain better quality of life and improved possibility to conceive spontaneously or optimize their chances of conception.

/pdf/lifestyle-and-fertility-the-influence-of-stress-and-quality-27cvii1d06.pdf

Lifestyle and fertility: the influence of stress and quality of life on male fertility.

Research investigating the role of paternal age in adverse birth outcomes is limited. This population-based retrospective cohort study used the Missouri maternally linked data set from 1989 to 2005 to assess whether paternal age affects fetal birth outcomes: low birth weight (LBW), preterm birth (PTB), stillbirth, and small size for gestational age (SGA). We examined these outcomes among infants across seven paternal age-groups ( 45 years) using the generalized estimating equation framework. Compared with infants born to younger fathers (25-29 years), infants born to fathers aged 40 to 45 years had a 24% increased risk of stillbirth but a reduced risk of SGA. A 48% increased risk of late stillbirth was observed in infants born to advanced paternal age (>45 years). Moreover, advanced paternal age (>45 years) was observed to result in a 19%, 13%, and 29% greater risk for LBW, PTB, and VPTB (very preterm birth) infants, respectively. Infants born to fathers aged 30 to 39 years had a lower risk of LBW, PTB, and SGA, whereas those born to fathers aged 24 years or younger had an elevated likelihood of experiencing these same adverse outcomes. These findings demonstrate that paternal age influences birth outcomes and warrants further investigation.

https://journals.sagepub.com/doi/pdf/10.1177/1557988312440718

The Effect of Paternal Age on Fetal Birth Outcomes

Dietary patterns in Mexican children and adolescents: Characterization and relation with socioeconomic and home environment factors.

The study purpose was to assess the relationship between various grades of preterm birth (moderate preterm: 33–36 weeks; severe preterm: 27–32 weeks; extreme preterm: ≤ 26 weeks) in the first pregnancy and neonatal mortality (death within 28 days of birth; early: 0–7 days; late: 8–28 days) in the second pregnancy. Using the Missouri maternally-linked dataset (1989–2005), a population-based, retrospective cohort analysis with propensity score-weighted matching was conducted on mothers with two consecutive singleton live births (n = 310,653 women). Women with a prior preterm birth were more likely to subsequently experience neonatal death. The odds increased in a dose-dependent pattern with ascending severity of the preterm event in the first pregnancy (moderate preterm: AOR = 1.32; 95% CI: 1.10–1.60; severe preterm: AOR = 2.62; 95% CI: 2.01–3.41; extreme preterm: AOR = 5.84; 95% CI: 4.28–7.97; p value for trend < 0.001). However, the pathway for the relationship between prior preterm birth and subs...

Preterm birth in the first pregnancy and risk of neonatal death in the second pregnancy: A propensity score-weighted matching approach

AIM: The aim of this paper was to assess the association between all-cause infant mortality (death<365 days) in the first pregnancy and the risk of preterm birth (<37 weeks of gestation) in the second pregnancy. METHODS: Using the Missouri maternally linked dataset from 1989 to 2005 (N.=639134 singleton live births), we conducted a population-based retrospective cohort analysis with women who had two singleton births between 1989 and 2005. We employed Cox Proportional Hazards Regression to generate adjusted hazard ratios (AHR) and 95% confidence intervals (CI) to approximate relative risks. RESULTS: Prior infant mortality was associated with an increased risk for preterm birth in the second pregnancy (AHR=1.96, 95% CI=1.80-2.13). For black women, the risk of preterm birth following infant mortality was more than three-fold (AHR=3.37, 95% CI=2.92-3.89), while the risk for white women was twice as high (AHR=2.04, 95% CI=1.86-2.26) (referent=white women without infant death in the first pregnancy). CONCLUSION: Women with a history of infant mortality are at risk for preterm birth in subsequent pregnancies. This risk was significantly elevated for black women. These findings provide further evidence that previous childbearing experiences play a critical role in the occurrence of adverse feto-infant outcomes.

All-cause infant mortality and the risk for subsequent preterm birth.

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The Effect of Paternal Age on Fetal Birth Outcomes

Dietary patterns in Mexican children and adolescents: Characterization and relation with socioeconomic and home environment factors.

Preterm birth in the first pregnancy and risk of neonatal death in the second pregnancy: A propensity score-weighted matching approach

All-cause infant mortality and the risk for subsequent preterm birth.