Table 2.

Impact of maternal nutrition on offspring’s CVD related outcomes

Authors (Year), country, study type	Subjects (n, age range)	Data collection method	Maternal nutrition exposure	Outcome
Reynolds RM, et al [14] (2013). United Kingdom, Retrospective Cohort	37 709 (7134 exposed to ow/ob), 34-61 y	Maternal BMI taken at first ANC within the ABC. Linked to national death and morbidity records	Maternal weight during pregnancy (overweight 25-29.9, obesity >30)	Hazard ratio for CVD event related hospital admissions in offspring: Maternal BMI <18.5 kg/m2 = 0.90 (95%CI = 0.63-1.00); Maternal BMI 25-29.9 kg/m2 = 1.15 (95% CI = 1.04-1.26); Maternal BMI>30 kg/m2 = 1.29 (95% CI = 1.06- 1.57)
				Hazard ratio for cerebrovascular disease in offspring: Maternal BMI <18.5 kg/m2 = 0.64 (95% CI = 0.20-2.05); Maternal BMI 25-29.9 kg/m2 = 1.61 (95% CI = 1.10-2.36); Maternal BMI>30 kg/m2 = 1.54 (95% CI = 0.69-3.42)
				Maternal overweight and obesity were associated with a significant increase in CVD related hospital admissions in offspring. Maternal overweight was also associated with a significant increase in cerebrovascular disease in offspring. No significant association was found for angina, myocardial infarction, stroke or peripheral artery disease in offspring. Risk of premature death (<55 y) was 40% higher for offspring of obese mothers (HR = 1.4, 95% CI = 1.17-1.68).
Bhattacharya S, et al [15] (2015). United Kingdom, Retrospective Cohort	N = 3781 43-49 y	The ABC of the 1950s – linked with local obstetric and national vital statistics and hospital clinical data sets	Gestational weight gain (GWG)	For offspring whose mothers had a rate of GWG of ≥1 kg/week demonstrated a significantly higher risk of suffering a cerebrovascular event (aHR = 2.70, 95% CI = 1.19-6.12). The risk of suffering a cardiovascular event (aHR = 1.37, 95% CI = 0.59-3.18), or mortality (aHR = 0.47, 95% CI = 0.07, 3.10) was not significantly higher. There were no significant associations between lower rates of GWG and CVD outcomes.
Eriksson JG, et al [16] (2011). Finland, Retrospective Cohort	N = 6975 men (655 cases of CHD), 58-63 y	HBC – linked to offspring hospital admissions and deaths using national identification numbers	Maternal weight during pregnancy	For mothers with height >160 cm and BMI>25 kg/m2 during pregnancy: Offspring who had a low ponderal index ≤25 kg/m3 had an elevated risk of CHD (HR = 1.9 (95% CI = 1.1-3.2), P for trend with reducing ponderal index trend = 0.01; Offspring who had a low placental weight ≤550 g had an elevated risk of CHD (HR = 2.2, 95% CI = 1.3-4.0), P for trend with reducing placental weight = 0.002
				Of mothers with height >160 cm and BMI <25 kg/m2 during pregnancy: Offspring with placental/ birth weight (%)>20.5% had an increased CHD risk (HR = 1.8, 95% CI = 1.1-3.0), P for trend with increasing percentage = 0.01
				These relationships were not apparent according to BMI in women under <160 cm
Forsen T, et al [17] (1997). Finland, Retrospective Cohort	3302 men, 47-71 y	Data from men within the HBC. Linked to national mortality register	Maternal BMI in late pregnancy	Risk of CHD rose with every standard deviation increase in mothers BMI (HR = 1.24, 95% CI = 1.10-1.39, P = 0.0004), mean BMI was 26.9
				For mothers with height <1.58 m the risk of CHD in offspring rose with increasing BMI (BMI>30: mortality ratio 171 vs BMI <25: mortality ratio 56, P = 0.006)
				No significant association in mothers >1.58 m tall.
Eriksson JG, et al [18] (2014). Finland, Retrospective Cohort	N = 13 345, 70-80 y	Offspring of the HBC – maternal BMI measured prior to delivery and linked to offspring’s national health records	Maternal overweight in pregnancy	Offspring’s risk of CVD increased significantly with increasing maternal BMI (BMI ≤24 kg/m2 HR = 1.0 vs BMI ≥28 kg/m2 HR = 1.13) with HR = 1.026 trend per kg/m2, 95% CI = 1.010-1.042, P for trend = 0.002)
				Offspring’s risk of CHD increased significantly with increasing maternal BMI (BMI ≤24 kg/m2 HR = 1.0 vs BMI ≥28 kg/m2 HR = 1.13) with HR = 1.030 trend per kg/m2, 95% CI = 1.010- 1.050, P for trend = 0.003)
				Offspring’s risk of CHD increased significantly with increasing maternal BMI (BMI ≤24 kg/m2 HR = 1.0 vs BMI ≥28 kg/m2 HR = 1.13) with HR = 1.030 trend per kg/m2 = , 95% CI = 1.010- 1.050, P for trend = 0.003)
Painter RC, et al [19] (2006). Netherlands, Case Control	N = 2414 (385 exposed), 50-58 y	Medical records of mothers within DFBC. Offspring identified by council records and results measured during hospital visit	Maternal exposure to famine during early, mid, late pregnancy (<1000 cal/d)	The only significant increase in CAD was seen in offspring whose mothers were exposed in early gestation (cumulative incidence 13% vs 8% in non-exposed, aHR = 1.9 (95% CI = 1.0-3.8, P < 0.05) and the age of onset was two years younger (47 y vs 49 y, P < 0.05)
				Compared to mothers not exposed to famine, maternal weight gain in the last trimester, and weight at the end of pregnancy was significantly lower (by 1 kg and 2 kg respectively, P < 0.005).
Bygren LO, et al [20] (2000). Sweden, Retrospective Cohort	N = 7572 (exposed), 40-70 y	Subjects born in the parish of Skellefteå, Sweden between 1805 and 1849 and living there at the age of 40.	Exposure to famine during pregnancy	The relative risk (RR) of sudden death was almost doubled for those whose mothers were exposed to famine in early gestation, and a good harvest in late gestation (RR = 1.99, 95% CI = 1.22-3.25)
				Similar risk was evident where there was plentiful food supply in early gestation and famine exposure in late gestation (RR = 1.68, 95% CI = 1.03-2.75)
				Poor food availability throughout pregnancy was not associated with CVD related sudden death (RR = 0.98, 95% CI = 0.55-1.58).
Van Abeelen AF, et al [21] (2012). Netherlands, Retrospective Cohort	1991, 18-64 y	Offspring from the DFBC (Linked to Statistics Netherlands mortality data).	Exposure to famine during pregnancy	206 subjects (10%) had died at the time of analysis
				Women exposed to famine in early gestation had a significantly higher risk of cardiovascular mortality (HR = 4.6, 95% CI = 1.2-17.7, P = 0.03)
				Men exposed to famine in early gestation showed a non-significant reduction in cardiovascular mortality (HR = 0.9; 95% CI = 0.3, 3.1, P = 0.90)
				Exposure to famine in mid and late gestation was not associated with significantly increased morality from any cause in men and women.
Ekamper P, et al [22] (2015). Netherlands, Retrospective Cohort	41 096 men (22 952 exposed), 63 y	Male conscripts born between into the DFBC. Linked to military health records.	Exposure to famine during pregnancy (<900 kcal/d)	CVD accounted for 28.3% of recorded deaths but this did not indicate a significant increase in CVD related mortality following gestational exposure to famine (HR = 1.07, 95% CI = 0.91-1.26), or pre-pregnancy exposure (HR = 1.13, 95% CI = 0.94-1.36)
				There was no significant increase in cerebrovascular disease following maternal exposure to famine before or during gestation (HR = 1.02, 95% CI = 0.72-1.44).

aHR – adjusted hazard ratio, ANC – ante-natal clinic, ABC – Aberdeen Birth Cohort, BMI – body mass index, CAD – coronary artery disease, Cal – calorie, CHD – coronary heart disease, CI – confidence interval, CVD – cardiovascular disease, DFBC – Dutch Famine Birth Cohort, GWG – gestational weight gain, HBC – Hamamatsu Birth Cohort, HR – heart rate, y – years