Advanced Maternal Age and the Risk of Major Congenital Anomalies

Objective This study aims to determine if advanced maternal age (AMA) is a risk factor for major congenital anomalies, in the absence of aneuploidy. Study Design Retrospective cohort study of all patients with a singleton gestation presenting for second trimester anatomic survey over a 19-year study period. Aneuploid fetuses were excluded. Study groups were defined by maternal age ≤ 34 and ≥ 35 years. The primary outcome was the presence of one or more major anomalies diagnosed at the second trimester ultrasound. Univariable and multivariable logistic regression analyses were used to estimate the risk of major anomalies in AMA patients. Results Of 76,156 euploid fetuses, 2.4% (n = 1,804) were diagnosed with a major anomaly. There was a significant decrease in the incidence of major fetal anomalies with increasing maternal age until the threshold of age 35 (p < 0.001). Being AMA was significantly associated with an overall decreased risk for major fetal anomalies (adjusted odds ratio: 0.59, 95% confidence interval: 0.52–0.66). The subgroup analysis demonstrated similar results for women ≥ 40 years of age. Conclusion AMA is associated with an overall decreased risk for major anomalies. These findings may suggest that the “all or nothing” phenomenon plays a more robust role in embryonic development with advancing oocyte age, with anatomically normal fetuses being more likely to survive

Efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12, pregnancy-associated plasma protein A, and maternal characteristics in the prediction of preeclampsia

OBJECTIVE: To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia. METHODS: This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics. RESULTS: Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. CONCLUSION: First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency

Advanced Maternal Age and the Risk of Major Congenital Anomalies

Objective: This study aims to determine if advanced maternal age (AMA) is a risk factor for major congenital anomalies, in the absence of aneuploidy. Study Design: Retrospective cohort study of all patients with a singleton gestation presenting for second trimester anatomic survey over a 19-year study period. Aneuploid fetuses were excluded. Study groups were defined by maternal age ≤ 34 and ≥ 35 years. The primary outcome was the presence of one or more major anomalies diagnosed at the second trimester ultrasound. Univariable and multivariable logistic regression analyses were used to estimate the risk of major anomalies in AMA patients. Results: Of 76,156 euploid fetuses, 2.4% (n = 1,804) were diagnosed with a major anomaly. There was a significant decrease in the incidence of major fetal anomalies with increasing maternal age until the threshold of age 35 (p \u3c 0.001). Being AMA was significantly associated with an overall decreased risk for major fetal anomalies (adjusted odds ratio: 0.59, 95% confidence interval: 0.52–0.66). The subgroup analysis demonstrated similar results for women ≥ 40 years of age. Conclusion: AMA is associated with an overall decreased risk for major anomalies. These findings may suggest that the “all or nothing” phenomenon plays a more robust role in embryonic development with advancing oocyte age, with anatomically normal fetuses being more likely to survive