4 Discussion
Preterm birth is responsible for about 80 % of all healthcare costs in the first year of life. Using recent estimates of therapeutic efficacy for existing treatments to prevent early PTB (in this instance, low dose aspirin and vaginal progesterone) employing detection rates that have been achieved with FutureBIRTH™, the current study of the impact of universal screening of pregnant women reaching 11–19 weeks shows a potential cost reduction for the US healthcare system of $61 million per 100,000 pregnancies net of screening and treatment costs, assuming a detection rate of 80 % for both sPTB≦32 weeks and EOP. Nationwide, universal screening of the 3.8 million pregnancies in the US annually at $750 per patient with detection rates between 60 and 80 % would avoid between $1.0–2.3 billion in direct healthcare costs annually.
Although our analysis was based on US data, we have expanded our analysis to look at the impact of screening should the population in question have a lower incidence of PTB≦32 weeks. Universal screening remained cost-effective even when the population screened had an incidence rate of 0.46 %, one-fifth of that of the US, with an 80 % detection rate. While the cost of healthcare delivery may well be different, the likelihood of local applicability is high.
Our findings were similar to those published by Caughey et al.27 with several important differences. Most notably, the test that they envisioned did not exist at the time, but it does now. FutureBIRTH™ fulfills their test criteria while the estimated cost of the test was lower than Caughey et al. suggested. Furthermore, our assumed efficacy for progesterone (38 %) was less than half of what Caughey et al. assumed it would be. In addition, FutureBIRTH™ is the only test performed before 20 weeks that accurately and independently predicts the future development of both sPTB and EOP.
Our estimates are likely an underestimate of the societal cost savings accrued by universal screening as they include only conservative estimates of direct medical costs for the delivery and the first year of life. Hall and Greenberg28 found that preterm infants have poorer educational and labor force outcomes, and Hirschberger et al.29 reported that among children born ≦32 weeks, 25 % had cognitive impairment at the age 10 years, 11 % had cerebral palsy, 7 % were diagnosed with autism spectrum disorder, and 7 % were diagnosed with epilepsy. Stevens et al.30 found that of children born within 28–32 weeks of gestation to women with EOP, 2.7 % died, 41.3 % experienced respiratory distress, 20.3 % had sepsis, 5.9 % an interventricular hemorrhage (IVH), and 3.9 % had retinopathy of prematurity. Further, 3 % of the mothers experienced acute renal failure, 3 % seizures, 5.2 % thrombocytopenia, and 0.2 % died. They estimated that the average cost of EOP≦32 weeks for delivery plus 18 months thereafter totaled $311,701 per mother and child. By avoiding 40–50 % of births ≦32 weeks, the direct and indirect cost savings would be massive.
In 2018, US Medicaid31 insured 43 % of all births while commercial carriers covered 49.1 %. Medicaid paid for a greater share of births in rural areas, among women under 19 years, and women with lower levels of educational attainment-all of which are considered risk factors for PTB. Medicaid also paid for a greater share of Black, Hispanic, American Indian, and Alaska Native women's births. Two-thirds of women covered by Medicaid have had a prior birth and 6 % a prior PTB. In addition, more than half of the women with Medicaid-covered births were either overweight or obese and almost 15 % smoked tobacco prior to pregnancy. One percent of women covered by Medicaid had pre-pregnancy diabetes and 2 % had pre-pregnancy hypertension, both of which are risk factors for PTB and EOP. The share of women with potential complicating health conditions was similar across rural and urban areas for those covered by Medicaid except for tobacco use, which was more prevalent in rural areas. Eleven percent of infants born to Medicaid-covered mothers and 9 % of those born to privately insured and uninsured women delivered <37w. The Medicaid rate of preterm births (<37 weeks) was highest in Mississippi (14.4%) and lowest in Vermont (8.7%). It is unlikely Medicaid costs are lower than those modeled in the current study, and would therefore also support universal screening as outlined in this study as cost-effective.
It has been argued the risk of aspirin is so low, that all women should take low-dose aspirin (variously defined as 60 mg–150 mg qd) throughout pregnancy. Excluding the risk of severe allergy, there are at least three potential flaws to this position. The first is patient compliance. Prevention of EOP is compliance-dependent with the optimal compliance rate >90 %.9 While there are no studies of pregnant women outside of clinical trial conditions, there have been several studies of patients prescribed secondary therapy for a prior myocardial infarction. Risk factors associated with poor adherence (defined as in those studies as <50 % of prescribed tablets) include common pregnancy risk factors such as cigarette smoking, obesity, and a lack of exercise.32 Compliance with an aspirin regimen in patients with a prior myocardial infarction was particularly low- 65 % (53 %–77 %).33 It seems unlikely that the compliance of young, self-described healthy women who lack the motivational fear of suffering another myocardial infarction will be higher. The second flaw is the potential for unexpected outcomes secondary to aspirin. Petersen et al.34 noted more than a doubling of bilateral spastic cerebral palsy in children exposed to aspirin across gestation.
The final potential flaw is that low-dose aspirin does not appear to lower PTB rates from PPROM or spontaneous labor when given to all nulliparas,35 but rather reduces only those PTBs associated with hypertension.36 If true, universal aspirin would not address more than two-thirds of the births ≤32 weeks. Taken together, while the simplicity and availability of universal aspirin treatment are appealing, it will not solve the problem of extreme PTB and may make the outcomes worse. Targeted therapy would minimize unnecessary exposure and provide a compliance incentive.
The impact of supplemental progestogens for the prevention of sPTB remains controversial. And while several professional organizations consider vaginal progesterone a standard of care for certain indications,19 there is no consensus on its effectiveness25,37,. We have utilized the most up-to-date and comprehensive meta-analysis to illustrate the potential impact of vaginal progesterone as a potential 38 % reduction in PTB≦32 weeks, but realize whether the current treatment is progesterone, cervical cerclage, or pessary, new targeted treatments for sPTB are desperately needed. The prospect of being able to objectively identify a high-risk pool of subjects in early pregnancy should benefit future therapeutic trials. Also, since the financial costs of PTB≦32 weeks represent the majority of all health care costs in the first year of life, even a small decrease in the PTB≦32 weeks rate could be cost-effective. Further, vaginal progesterone is no longer the only option. After the completion of this study, Carlson et al. published the results of a randomized clinical trial demonstrating a DHA supplement of 1000 mg per day given to at risk women decreased PTB≦32 by 50 %.38
In conclusion, universal screening of pregnant women with a singleton before 20 weeks with either FutureBIRTH™ or some yet to be discovered panel combined with current preventative therapy has the potential to reduce PTB≦32 weeks by 40 %–50 %, freeing up families and societies from the burden of extreme PTB.
