Non-Syndromic Cleft Lip and Palate: Could Stress be a Causal Factor?

Non-Syndromic Cleft Lip and Palate: Could Stress be a Causal Factor?



Graeme H. Wallace OAM, KCSJ, MHSc, Jacinta M. Arellano PHd, Tini M. Gruner PHd.


Cite this Article as:

Wallace, G. H., J. M. Arellano, et al. (2011). "Non-syndromic cleft lip and palate: Could stress be a causal factor?" Women and Birth 24(1): 40-46.



School of Health & Human Sciences, Southern Cross University, Lismore, New South Wales, Australia

Received 28 June 2010; received in revised form 11 August 2010; accepted 11 August 2010





The aetiology of non-syndromic cleft lip and palate has as yet not been clearly defined. Familial relationships, environmental toxins and nutritional status have all been considered without positive results, although in some studies a potential link between non-syndromic cleft lip and palate and any one or more of these factors has been proposed.

This qualitative study, which involved families living in three States of Australia, suggests that physical and/or emotional stress may well be implicated in clefting. While little work has been done in considering stress as a causal factor, the existing literature suggests, as does this study, that elevated stress levels at, or soon after, conception appear to affect foetal development.

Elevated stress, particularly an extended term of traumatic stress, can lead to oxidative damage at the cellular level via Hypothalmus – Pituitary – Adrenal (HPA) axis dysregulation, and high cortisol and cytokine production. The effect of this hormonal shift is to re-direct the blood supply to the mother’s muscles, thereby reducing the supply to the placenta, causing a potential nutritional deficiency which may then result in a genetic alteration in the foetus.



Three forms of oral defects have been considered: cleft lip (CL), cleft palate (CP) and cleft lip and palate (CLP). Throughout this paper the letters ‘U’ will be used for unilateral and ‘B’ for bilateral and the abbreviation CLP will be used as a generic term unless stated otherwise.

The aetiology of non-syndromic CLP, a state where either the lip or palate or both have not completely formed, has to date not been adequately determined. Most researchers suggest that the cause is multi-factorial.

Non-syndromic clefting is distinct from syndromic clefting in that the clefts to the lip and/or palate are the only anomalies, while in syndromic clefting the cleft occurs with other well-documented abnormalities, such as respiratory or cardiac anomalies. Syndromes that are associated with clefting are Van der Woude, Teacher-Collins and Pierre Robin as well as several others. In these cases the clefting is generally the lesser of the concerns.

CLP has been recognized for many centuries. The earliest known reported reference to clefting comes from China1 where it is claimed that in AD 390 an unknown surgeon successfully closed a cleft on an 18 year old girl, ‘Wei Yang-Chi’, who later became the Governor General of several provinces.

More rigorous research into CLP appears to have started early in the 20th century2, but no clear linkages have been established that point to definitive causative factors as the cause could well be a combination of one or more factors. Research papers covering genetics, familial associations, nutrition, drug use by the mother and environmental toxins have been canvassed to determine whether there could be any connection which may lead to a better understanding of the nature of this problem. This investigation focuses solely on the role of stress immediately before or at an early stage in the pregnancy in the cause of these anomalies.

Stress levels affect the metabolism and thus the environment in which the cells reproduce and develop. If stress levels are low or of short duration, physiology and cell development and replication can return to normal, while continuously high stress levels lead to possible abnormal development or cell necrosis 3. The development and function of foetal tissue and organs is directly proportional to the amount of blood they receive. When passing through the placenta, the hormones of a mother experiencing stress will profoundly alter the distribution of blood flow in her foetus and change the character of her developing child’s physiology 4, 5.




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