Reconsidering the developmental origins of adult disease paradigm: The 'metabolic coordination of childbirth' hypothesis.

In uncomplicated pregnancies, birthweight is inversely associated with adult non-communicable disease (NCD) risk. One proposed mechanism is maternal malnutrition during pregnancy. Another explanation is that shared genes link birthweight with NCDs. Both hypotheses are supported, but evolutionary perspectives address only the environmental pathway. We propose that genetic and environmental associations of birthweight with NCD risk reflect coordinated regulatory systems between mother and foetus, that evolved to reduce risks of obstructed labour. First, the foetus must tailor its growth to maternal metabolic signals, as it cannot predict the size of the birth canal from its own genome. Second, we predict that maternal alleles that promote placental nutrient supply have been selected to constrain foetal growth and gestation length when fetally expressed. Conversely, maternal alleles that increase birth canal size have been selected to promote foetal growth and gestation when fetally expressed. Evidence supports these hypotheses. These regulatory mechanisms may have undergone powerful selection as hominin neonates evolved larger size and encephalisation, since every mother is at risk of gestating a baby excessively for her pelvis. Our perspective can explain the inverse association of birthweight with NCD risk across most of the birthweight range: any constraint of birthweight, through plastic or genetic mechanisms, may reduce the capacity for homeostasis and increase NCD susceptibility. However, maternal obesity and diabetes can overwhelm this coordination system, challenging vaginal delivery while increasing offspring NCD risk. We argue that selection on viable vaginal delivery played an over-arching role in shaping the association of birthweight with NCD risk.

Completeness and usability of ethnicity data in UK-based primary care and hospital databases.

BACKGROUND: Ethnicity recording across the National Health Service (NHS) has improved dramatically over the past decade. This study profiles the completeness, consistency and representativeness of routinely collected ethnicity data in both primary care and hospital settings. METHODS: Completeness and consistency of ethnicity recording was examined in the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES), and the ethnic breakdown of the CPRD was compared with that of the 2011 UK censuses. RESULTS: 27.1% of all patients in the CPRD (1990-2012) have ethnicity recorded. This proportion rises to 78.3% for patients registered since April 2006. The ethnic breakdown of the CPRD is comparable to the UK censuses. 79.4% of HES inpatients, 46.8% of outpatients and 26.8% of A&E patients had their ethnicity recorded. Amongst those with ethnicity recorded on >1 occasion, consistency was over 90% in all data sets except for HES inpatients. Combining CPRD and HES increased completeness to 97%, with 85% of patients having the same ethnicity recorded in both databases. CONCLUSIONS: Using CPRD ethnicity from 2006 onwards maximizes completeness and comparability with the UK population. High concordance within and across NHS sources suggests these data are of high value when examining the continuum of care. Poor completeness and consistency of A&E and outpatient data render these sources unreliable.