Background:

Pregnancy represents a metabolic challenge to women - in a normal pregnancy, a woman will become relatively insulin resistant, hyperlipidaemic, and have an up-regulation of coagulation factors and the inflammatory cascade (Sattar) in order to support the pregnancy. Most (Green et al.; Ness et al.; Parikh), but not all (Steenland) studies have found a positive association between parity and CVD in later life, suggesting that the more pregnancies a women has in her lifetime, the greater her risk of cardiovascular disease. However the mechanisms underlying this association are poorly understood. One possibility is that the stress test of pregnancy has long term effects and indeed there is some evidence to support this.

To our knowledge, no study has examined the association of inter-pregnancy interval and later cardiovascular health. It is possible that exposure to multiple pregnancies within a short time frame may be a risk factor for later cardiovascular health, since the woman's metabolic system would have less time to recover to its usual state between pregnancies.

Shorter inter-pregnancy interval may also be associated with greater gestational weight gain, which in ALSPAC has been shown to be associated with adverse outcomes in both the mother and offspring (Fraser 2010; Fraser 2011).

Aims:

To examine the association of inter-pregnancy interval with i) gestational weight gain, and ii) ii) cIMT, arterial stiffness and cardiovascular risk factors measured approximately 17 years postpartum in the mothers of the Avon Longitudinal Study of Parents and Children (ALSPAC).

Exposure variable:

Inter-pregnancy interval (analysis restricted to women who have 2 offspring in order to remove confounding by parity)

Outcome variables:

1. Gestational weight gain - as modelled using linear spline multilevel models by Kate Tilling and used in previous publications (Fraser 2010; Fraser 2011). Since these data are only available for the index child of ALSPAC, these analysis will be restricted to women where the ALSPAC index child is their second child, and they have no further children. The association between inter-pregnancy interval and gestational weight gain will be assessed by fitting an interaction between a categorised indicator of inter-pregnancy interval (short, medium (reference), long) and gestational age in the multilevel model of gestational weight gain

2. ii) cIMT, arterial stiffness and Cardiovascular risk factors measured at the 'focus on mothers' clinic 18 years postpartum. Detailed measures to be examined are the calculated 10-year risk of CVD based on the Framingham risk score, cIMT, arterial stiffness, BMI, waist circumference, systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, insulin, pro-insulin, triglycerides, and C-reactive protein. Linear or logistic regression will be used to assess the association between interpregnancy interval and each outcome.

Confounding variables:

Maternal age at delivery and parity were obtained from obstetric records. Information on further pregnancies was obtained from various questionnaires. Information on prepregnancy weight and height, maternal smoking in pregnancy, maternal education, and household social class was based on questionnaire responses. Maternal education was categorized as below or above university level. The highest parental occupation was used to allocate the children to family social class groups (classes I [professional/managerial] to V [unskilled manual workers], according to the 1991 British Office of Population and Census Statistics classification). Maternal smoking in pregnancy was categorized as follows: never smoked; smoked before pregnancy or in the first trimester and then stopped; and smoked throughout pregnancy.

Additional relevant variables:

Information on diabetes mellitus and CVD diagnosed during follow-up was collected by a questionnaire completed 18 years after the index pregnancy. Women reported having been told they had a heart attack, heart failure, angina, and/or stroke.

References:

Fraser A, Tilling K, Macdonald-Wallis C, Sattar N, Brion MJ, Benfield L, Ness A, Deanfield J, Hingorani A, Nelson SM, Smith GD, Lawlor DA (2010). Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood. Circulation;121:2557-64

Fraser A, Tilling K, Macdonald-Wallis C, Hughes R, Sattar N, Nelson SM, Lawlor DA. (2011) Associations of gestational weight gain with maternal body mass index, waist circumference, and blood pressure measured 16 y after pregnancy: the Avon Longitudinal Study of Parents and Children (ALSPAC); Am J Clin Nutr. 93: 1285-92

Green A, Beral V, Moser K (1988) Mortality in women in relation to their childbearing history. BMJ; 297: 391-395.

Ness RB, Harris T, Cobb J, Flegal KM, Kelsey JL, et al. (1993) Number of pregnancies and the subsequent risk of cardiovascular disease. N Engl J Med; 328: 1528-1533.

Parikh NI, Cnattingius S, Dickman PW, Mittleman MA, Ludvigsson JF, et al. (2010) Parity and risk of later-life maternal cardiovascular disease. American Heart Journal; 159: 215-221

Sattar, N. (2004) Do pregnancy complications and CVD share common antecedents? Atherosclerosis Supplements; 5: 3-7

Steenland K, Lally C, Thun M (1996) Parity and coronary heart disease among women in the American Cancer Society CPS II population. Epidemiology; 7: 641-643.