The concept of perinatology was first brought up by Dr. Erich Saling in the 1970s [
1]. It bridges between prenatal and postnatal periods and commonly covers from 28 weeks of gestation to 28 days postpartum. The formation of perinatology has led to close collaboration between obstetricians and neonatologists for the wellbeing of the mother and newborn. Despite the close ties, the role of a neonatologist tends to be passive until a baby is born.
In recent years, the theory of developmental origins of health and disease emphasizes the significance of events in early life for the health in later age [
2]. This concept prompts pediatricians to pay attention to the health of the fetus and has pushed the frontier of pediatrics into fetal, embryonic stage and even preconception. For example, gestational diabetes mellitus (GDM), a common pregnancy complication affecting more than 10% of pregnant women in the world, is a significant risk factor for childhood obesity and neurodevelopmental disorders [
3]. Early interventions to control for GDM can avert the harmful effects on the long-term health of the offspring.
Likewise, fetal exposure to environmental pollutants and substances such as cannabis is associated with developmental disorders [
4]. The role of a pediatrician in the research and understanding of the environment that the fetus was exposed to is essential for screening and milestone assessment in children. Pediatric interventions such as immunizations can begin
in utero. Vaccination of the mother with tetanus, diphtheria, and pertussis, for instance, protects children from pertussis [
5]. There is also evidence that COVID-19 vaccination transfers protective antibodies to the newborn [
6]. Long-term studies of these interventions are vital to establish safety and efficacy, requiring an
in utero pediatric lens.
Postpartum “reprogramming” for infants compromised
in utero can also play an important role in preventing adult diseases. How to feed small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants to avoid inappropriate catch-up or catch-down growth in infancy and early childhood has been a long-standing challenge because the etiology of abnormal fetal growth is complex and diverse [
7]. While obstetricians may perform various tests to search for the causes of SGA, for example, information on detailed fetal assessment as well as placental pathology is often not readily available to or underused by child health care providers. Consequently, personalized therapies for various SGA etiologies remain underdeveloped. Pediatricians need to be more versed in the antepartum care, and multidisciplinary efforts that involve maternal-fetal medicine specialists and pediatricians are needed to address the practical gaps in caring for children with
in utero disorders. These issues that were traditionally considered as maternal-fetal medicine problems now become pediatricians’ concerns as well.
Furthermore, with rapid advances in fetal imaging technology and prenatal screening and diagnosis, more and more fetal structural as well as functional anomalies are being discovered
in utero. Pediatricians are increasingly involved in genetic counseling and treatment planning. When pediatricians are counseling couples with an affected baby or treating the child, an early prevention strategy for the next possible pregnancy is often discussed. Helped by improving intervention techniques,
in utero interventions have progressed from experimental concept to life saving practice during the past 2 decades [
8]. For certain conditions and anomalies, fetal stage has advantages for treatment. The developmental properties during fetal period may increase the efficiency and likelihood of success, better long-term prognosis with little sequelae. For instance, infants with spina bifida may suffer from paralysis, developmental delays, or brainstem dysfunction despite postnatal repair. The performance of fetal myelomeningocele surgery could relieve clinical symptoms, and reduce the likelihood of further ventriculoperitoneal shunt placement and improve child neurological functioning. The
ex utero intrapartum treatment (EXIT) procedure, known as “operation on placental support,” provides another opportunity for correcting congenital anomalies. Newborns with mechanical airway obstruction, which is fatal immediately after birth, may be operated by EXIT while the fetus is still oxygenated through utero-placental circulation.
Innovations in treatment techniques from open fetal operation to fetal endoscopic procedures have also facilitated and broadened the applications of fetal surgery [
8]. Percutaneous interventions are even less invasive to achieve the same therapeutic effects for certain conditions [
8]. Timely interventions of fetal aortic valvuloplasy for critical aortic stenosis may not only improve myocardial development and ventricular function, but also increase the possibility of biventricular repair postnatally. Nonetheless, it is important to bear in mind that the potential benefits for the baby and risks for the mother and prematurity need to be carefully balanced.
To maximize perinatal survival, restore organ structure and function, and improve postnatal outcomes, more and more pediatric subspecialists take part in the antenatal care of the fetus because fetal anomalies can involve any system and organ like pediatric disorders. A full spectrum of well-trained pediatric subspecialists may provide optimal care and continuity for the young patient after birth. Collaboration among subspecialists is essential, including but not limited to maternal-fetal medicine specialists, pediatric surgeons, neonatologists, geneticists, pediatricians, anesthesiologists, radiologists, and possibly others in the process of counseling, evaluation and care of both the fetus and the mother.
Given the importance of fetal health for child and even adult health, and increasing involvement of pediatricians in fetal care, we would expand the scope of pediatrics into fetus, and propose a concept of
in utero pediatrics [
7]. Specifically, we define
In utero Pediatrics as a discipline that focuses on pediatric diseases originated in the uterus, including all structural malformations, growth and developmental abnormalities and congenital organ function defects. It encompasses screening, diagnosis, treatment and prevention of such diseases from a fertilized egg all the way to adolescence (Fig.1).
In utero Pediatrics moves the pediatrician’s attention and research time point of the above diseases from postnatal to embryo, breaking the barrier that the traditional pediatric diagnosis and treatment of such diseases only start from the neonatal stage. As it emphasizes the whole course from embryo to adolescence, it differentiates itself from the current fetal medicine and pediatrics but remains as a branch of fetal medicine and pediatrics combined. It gives a full play to the advantages of sequential and comprehensive management of pediatrics in various stages of newborn, preschool, school-age and adolescence, and integrates the disciplinary advantages of prevention, treatment and rehabilitation. Since the declining fertility rate along with aging population is a major challenge facing many countries, in utero pediatrics can help fetuses with special needs and ensure them to have a healthy developmental trajectory. We believe that like the concept of perinatology, in utero pediatrics can have a long-term impact on children with congenital disorders, by providing continuity of care from in utero to childhood.
Notwithstanding the inherent overlaps between in utero pediatrics and fetology and perinatology, the distinctions are important to be recognized. Tab.1 presents the similarities and differences among these three disciplines.
Despite its promising future, in utero pediatrics is still a new and fast evolving field with crossing and merging disciplines. Most functions of fetal organs (e.g., blood pressure) are still difficult to measure; fetal compromises are often unrecognized until irreversible damages have incurred. Clinical research is much needed to meet the new demand for knowledge of screening, detection, prevention and treatment in early life. Questions on who needs to be treated and when and how to intervene clinically remain wide open for most fetal conditions. Due to still high technical barriers, risks for the mother, and ethical issues of research in fetal care, the task of filling the gap is huge and challenging. Yet, as long as we are clear about the direction, technical difficulties will eventually become surmountable. As the above figure indicates, pediatrician’s responsibility is to ensure a healthy trajectory from an embryo to a full potential adult.
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