Preconceptional care, where reproductive medicine meets obstetrics: the origins of lifetime health

‘‘Victorious warriors win first and then go to war, while defeated warriors go to war first and then seek to win.’’

—Sun Tzu, The Art of War

Infant mortality is widely used as a key indicator of the overall health of a community, country, or continent. Given that perinatal mortality accounts for two-thirds of infant deaths, it is understandable why optimizing the content, access, and delivery of prenatal care became the major focus of obstetrics during the 20th century. Herein we argue that preconceptional care will emerge in the 21st century as a key component of reproductive care and that two major disciplines, obstetrics and reproductive medicine, will join forces in a battle not only to reduce perinatal morbidity and mortality but to optimize health for mothers and children, as well as set the stage for adult life.

Every year, an estimated 3.6 million infants worldwide die within the first 4 weeks of life. Of these, preterm labor and delivery (which affect 10% of all births) and preeclampsia (5%) contribute to 1.5 million neonatal deaths during the first week of life and to 1.4 million stillborn babies [1]. Congenital anomalies affect 2%–3% of newborns whose parents had conceived naturally. Genetic disorders affect 1% of live births and are responsible for 18% of pediatric hospitalizations and 20% of infant mortality. Many of these genetic disorders are caused by recessive or X-linked genetic mutations carried by 85% of humans; yet this situation remains unaddressed unless extensive carrier screening tests are performed.

Twenty-two genetic conditions are present in 1%–2% of couples, conferring high risk of having an affected child. In the United States, approximately 1 in 300 live births carry a trisomy, half of which affect chromosome 21. This disorder leads as the genetic cause of intellectual and developmental disabilities. Occurrence of trisomy 21 varies in accordance with the mother’s age, ranging in prevalence between 1:40 and 1:2,000 deliveries. Yet infant morbidity and mortality statistics remain high, despite this wealth of knowledge and the advent of modern prenatal medicine.

Specialists in reproductive endocrinology and infertility have been primarily concerned with optimizing short-term outcome in the first trimester of pregnancy. On the other hand, obstetricians and maternal–fetal medicine specialists focus on issues surrounding the diagnosis, treatment, and prevention of the ‘‘great obstetrical syndromes’’ (e.g., preterm labor, pre-eclampsia, gestational diabetes, fetal growth disorders, fetal death), which largely emerge in the second and third trimesters. Thus far, these disciplines have been operating in parallel.

Multiple lines of evidence have now coalesced to support the concept that most complications of pregnancy emerge from disorders that have their origins in early pregnancy, at the time of implantation and placentation. Even more intriguing is a set of observations suggesting that abnormal decidualization underlies the predisposition to preeclampsia and other obstetric complications, such as preterm labor and fetal growth restriction.

Preconceptional care aims to optimize reproductive outcome before pregnancy is established. The concept of a ‘‘prepregnancy clinic’’ emerged in 1980, with the goal of addressing concerns about preterm labor and spontaneous abortion. In practice, preconceptional care thus far has consisted of general advice about improving lifestyle and optimizing the treatment of pre-existing conditions, such as diabetes, and a small group of interventions (e.g., folic acid to prevent neural tube defects, glucose control to prevent congenital anomalies in diabetic women, and smoking cessation).

An accumulating body of knowledge indicates that environmental factors have a profound effect on lifetime health (e.g., diet, body composition, metabolism, and stress). This is now so compelling that it calls for revisiting and reframing the advice provided to parents preparing for pregnancy [2]. Preconceptional care can be informed by emerging knowledge about pregnancy outcome. Prospective parents can be counseled on birth spacing, prevention of teenage pregnancy, optimization of weight, improved nutrition and micronutrient status, prevention and management of infectious diseases, as well as screening for/managing chronic conditions. This information can complement continuing efforts to reduce tobacco use, alcohol consumption, and abuse of drugs.

A national action plan for promoting preconceptional health and health care in the United States has already been proposed for implantation via integrated service delivery for mothers and children from pregnancy to birth, with a unified extension into the immediate postnatal period and childhood [3]. For one condition—pregestational diabetes—it has been argued that substantial health and financial burdens could be prevented by utilizing preconceptional care. Specifically, 2.2% of U.S. births occur in women with pregestational diabetes, and preconceptional care to reduce hyperglycemia has been estimated to prevent 8,397 birth defects and 1,872 perinatal deaths annually, with a discounted lifetime cost averted for the affected cohort of children averaging as high as $4.3 billion [4].

A major challenge in the 21st century is to consider how recently generated knowledge and technologies can improve preconceptional care. For example, the genetic risk of the couple wishing to conceive should be considered, and advice offered, so that they may assess the risk and costs of conceiving a child with a genetic condition. The endometrium can be prospectively investigated before pregnancy, given that emerging evidence links a decidualization defect inducing impaired cytotrophoblast invasion as a possible cause of pre-eclampsia and other obstetric syndromes (5). Detecting decidualization defects before conception would aid the development of targeted therapies that may consequently prevent severe pre-eclampsia. Finally, the existence of an endometrial microbiome with unknown implications in the development of intrauterine infections during pregnancy and delivery or preterm birth should be considered. These new approaches can inform preconceptional interventions.

We believe that a frontier in medicine and biology is the development of preconceptional care. Delivering a healthy baby—the most important battle for prospective parents—should be won before gestation is even initiated. The preconceptional period presents a unique window in time for diagnosis, treatment, and prevention. Recent evidence suggests that the convergence of reproductive medicine and obstetrics has great potential to unravel the mysteries behind the genesis of obstetric disease and the prevention of pregnancy complications. The benefits of these new strategies are for the future human being, the prospective parents, and society as a whole.