Thyroid hormones are important for normal development of the human central nervous system (CNS). It is well established in children with congenital hypothyroidism that neonatal thyroid hormone deficiency significantly impairs subsequent neurodevelopment. In these children, the period of thyroid hormone insufficiency, which can begin in utero and extend until thyroid status is restored to normal in the neonatal period, determines the severity and type of defect manifested. While prompt and optimal thyroid hormone supplementation, following newborn screening is associated with far improved outcome and near normal development, subtle specific neurodevelopmental differences are still detectable compared to euthyroid controls. Because the particular impairments reflect the exact period of thyroid hormone insufficiency postnatally, as well as during gestation, this implies that brain development is not only thyroid hormone dependent in the neonatal period, but also prior to birth.

The length of mammalian pregnancy is tightly regulated to assure the delivery of a newborn mature enough to survive the extra-uterine environment. A successful pregnancy requires near complete relaxation of the uterus for more than ninety-five percent of gestation, overcoming the inherent tendency of the myometrium to contract with stretch. This active and highly regulated process is called myometrial quiescence. It requires not only the near absence of myometrial contractions, but also its refractoriness to contractile agents.

Ancient Egyptian medical papyri (1550BC) emphasised diagnosis by examination as the cornerstone of the decision to treat or not to treat an ailment. Today the information about the likelihood of diagnosis (and related prognosis) that interventions purport to treat comes from a combination of tests as shown in Figure 1. In addition to easy-to-obtain history (risk factors and symptoms) and examination (signs), current testing includes sophisticated investigations (haematology, biochemistry, radiology, microbiology, etc), which can also be invasive and expensive. Obstetricians routinely incorporate many test results into decision-making concerning management of women at risk of preterm birth, but studies to examine the ways in which even a small number of these tests alter the benefit and harm of treatments are rare.

Fetal growth restriction (FGR) as a consequence of uteroplacental insufficiency is an important contributor to perinatal death, neonatal morbidity and long-term health problems. Progressive uteroplacental dysfunction leads to placental respiratory failure and fetal hypoxaemia, which triggers compensatory fetal haemodynamic changes including blood flow redistribution towards essential fetal organs (brain, heart and adrenal glands) at the expense of the other body systems. The duration of the compensatory phase is variable, sometimes lasting weeks, and appears not to have deleterious short-term consequences. With further disease progression, the compensatory mechanisms reach their limit and myocardial dysfunction occurs. Once the disease enters this decompensatory phase, the fetus is at high risk of multisystem organ failure and in-utero demise. There is no effective in-utero therapeutic intervention. The main aim of management is to deliver the baby when the risks of antenatal demise and irreversible end-organ dysfunction associated with further prolongation of the pregnancy are greater than the risks from delivery.