The effect of fertility treatment and socioeconomic status on neonatal and post-neonatal mortality in the United States.

OBJECTIVE: To determine the association between fertility treatment, socioeconomic status (SES), and neonatal and post-neonatal mortality. STUDY DESIGN: Retrospective cohort study of all births (19,350,344) and infant deaths from 2014-2018 in the United States. The exposure was mode of conception-spontaneous vs fertility treatment. The outcome was neonatal (<28d), and post-neonatal (28d-1y) mortality. Multivariable logistic models were stratified by SES. RESULT: The fertility treatment group had statistically significantly higher odds of neonatal mortality (high SES OR 1.59; CI [1.5, 1.68], low SES OR 2.11; CI [1.79, 2.48]) and lower odds of post-neonatal mortality (high SES OR 0.87, CI [0.76, 0.996], low SES OR 0.6, CI [0.38, 0.95]). SES significantly modified the effect of ART/NIFT on neonatal and post-neonatal mortality. CONCLUSIONS: Fertility treatment is associated with higher neonatal and lower post-neonatal mortality and SES modifies this effect. Socioeconomic policies and support for vulnerable families may help reduce rates of infant mortality.

Fertility treatment increases the risk of preterm birth independent of multiple gestations.

Objective: To investigate the complex interplay between fertility treatment, multiple gestations, and prematurity. Design: Retrospective cohort study linking the national Center for Disease Control and Prevention infant birth and death data from 2014 to 2018. Setting: National database from Center of Disease Control and Prevention. Patients: In total, 19,454,155 live-born infants with gestational ages 22-44 weeks, 114,645 infants born using non IVF fertility treatment (NIFT), and 179,960 via assisted reproductive technology (ART). Intervention: Noninvasive fertility treatment or ART vs. spontaneously conceived pregnancies. Main Outcome Measures: The main outcome assessed was prematurity. Formal mediation analysis was conducted to calculate the percentage mediated by multiple gestations. Results: Newborns born using NIFT or ART compared with those with no fertility treatment had a higher incidence of multiple gestation (no fertility treatment = 3.0%; NIFT = 24.7%; ART = 32.7%; P<.001) and prematurity (no fertility treatment = 11.2%; NIFT = 23.4%; ART = 28.4%; P<.001). Mediation analysis demonstrates that 76.8% (95% confidence interval [CI], 75.2%-78.1%) of the effect of NIFT on prematurity was mediated through multiple gestations. Similarly, 71.2% (95% CI, 70.8%-72.7%) of the effect of ART on prematurity is mediated through multiple gestation. However, the direct effect of NIFT on prematurity is 20.4% (95% CI, 19.0%-22.0%). The direct effect of ART was 24.7% (95% CI, 23.7%-25.6%). Conclusion: A significant proportion of prematurity associated with fertility treatment is mediated by the treatment itself, independent of multiple gestations.

Outcomes of Very Preterm Infants Conceived with Assisted Reproductive Technologies.

OBJECTIVE: To compare mortality and early respiratory outcomes of very preterm infants conceived via assisted reproductive technology (ART) vs spontaneously. STUDY DESIGN: We identified inborn infants (July 2014-July 2019) with gestational age <32 weeks (n = 439); 54 cases were ART conceived. Spontaneously conceived controls (n = 103) were matched by multiple gestation status and gestational age. Primary outcome was 1-year mortality. Secondary outcomes were receipt of respiratory support and supplemental oxygen at 7 and 28 days and 36 weeks of postmenstrual age. We evaluated the association between conception method and outcomes by logistic regression, with adjustment for sociodemographic status. RESULTS: Women who conceived via ART had increased rates of prepregnancy and gestational diabetes, and no differences in rates of hypertensive disorders. Infant 1-year mortality was not different by mode of conception (ART 11.8% vs spontaneous 7.1%, P = .49). Infants conceived by ART were less likely to receive respiratory support or supplemental oxygen at all time points, but this relationship only reached significance for receipt of oxygen at 28 days (ART 20.8% vs spontaneous 39.0%, P = .03); this remained true after adjustment for race/ethnicity and socioeconomic index. CONCLUSIONS: When controlling for gestational age and multiple gestation status, very preterm infants conceived following ART had similar outcomes as those conceived spontaneously.

Outcomes of pulmonary vascular disease in infants conceived with non-IVF fertility treatment and assisted reproductive technologies at 1 year of age.

BACKGROUND: Assisted reproductive technologies (ARTs) have been associated with the development of endothelial dysfunction. OBJECTIVE: To determine potential differences in outcomes associated with pulmonary vascular disease in infants born to mothers receiving any infertility treatment including ART and non-IVF fertility treatments (NIFTs). DESIGN/METHODS: The sample was derived from an administrative database containing detailed information on infant and maternal characteristics for live-born infants in California (2007-2012) with gestational age (GA) 22 to 44 weeks. Cases were defined as infants with ICD-9 code for pulmonary vascular disease (PVD) and records for ART/NIFT. Controls were randomly selected at a 1:4 ratio. The primary outcome was 1-year mortality. Crude and adjusted odds ratio (OR) with 95% confidence interval (CI) were calculated. RESULTS: We identified 159 cases and 636 controls. Mothers that utilized ART/NIFT were older, to be of the Caucasian race, to have pre-eclampsia, private insurance, and education >12 years (P < .001). Cases compared to controls were more premature, had lower birth weights, and were more often the product of a multiple gestation pregnancy (P < .001). Cases had a higher 1-year mortality (18.2% vs 9.1%; OR: 2.2; 95% CI: 1.4, 3.6), more severe PVD (86.2% vs 72.3%; OR: 2.4; 95% CI: 1.5, 3.9), and a longer hospital stay (66.7 ± 73.0 vs 32.5 ± 47.2 days; P < .001) than controls. However, when adjusting for GA these differences become statistically insignificant. CONCLUSION: Children born following ART/NIFT with PVD had increased mortality compared to infants with PVD but without ART/NIFT. The primary driver of this relationship is prematurity.