Long-term consequences of low birth weight and the role of neha - PowerPoint PPT Presentation

Caroline Fall Long-term consequences of low birth weight and the role of neha maternal nutrition

Coronary Heart Disease Mortality Men and women born in Hertfordshire 1911-1930 WOMEN MEN 100 100 n=5,585 n=10,141 80 80 60 60 40 40 20 20 0 0 ≤5.5 -6.5 -7.5 -8.5 -9.5 >9.5 ≤5.5 -6.5 -7.5 -8.5 -9.5 >9.5 Birthweight (pounds) Barker D et al. Lancet 1989; ii: 577-80; Osmond C et al. BMJ 1993; 307: 1519-24

Type 2 diabetes and IGT (pre-diabetes) Men and women aged 60-71 years, Hertfordshire (n=667) 45 45 IGT + DM % % DM 40 40 35 35 30 30 25 25 20 20 15 15 10 10 5 5 0 0 ≤5.5 -6.5 -7.5 -8.5 -9.5 >9.5 ≤5.5 -6.5 -7.5 -8.5 -9.5 >9.5 Birthweight (pounds) Weight at one year (pounds) BMJ 1991;303:1019-22, BMJ 1995;310:428-32

Type 2 diabetes or pre-diabetes Men and women aged 60-71 years, Hertfordshire (n=667) % 20 15 10 5 Obese (BMI >28) Overweight (BMI <28) 0 Normal (BMI <25) ≤6.5 -8.5 >8.5 Birthweight (lbs) BMJ 1991;303:1019-22, BMJ 1995;310:428-32

Small babies and infants…. • Coronary heart disease • Hypertension • Type 2 diabetes • COPD • Chronic kidney disease • Osteopenia • Poor mental health

Small babies and infants…. • Central adiposity • Low muscle mass • Altered endocrine responses eg insulin, cortisol and growth hormone • Inflammation • Hyperlipidaemia

‘Supply - line’ to the fetus Mother’s diet and nutrient Mother’s ability to mobilise and Uterine blood flow stores transport nutrients Placental structure and function Mother unable to supply nutrients to satisfy fetal demand FETAL UNDERNUTRITION Inadequate Adaptation to ‘building blocks’ reduce demand Kidneys Liver Pancreas Muscle, Brain HPA axis Fat, Bone Reduced nephron Altered zonation ↓ β cells ↓ Muscle and bone Appetite centres ↑ Cortisol numbers ↓ Insulin sensitivity ↓ Insulin secretion ↑ Fat Leptin resistance Early maturation ↓ IGF -1 ↓ Insulin sensitivity Central Insulin Hyperlipidaemia obesity resistance Hypertension Type 2 diabetes Coronary heart disease

‘Supply - line’ to the fetus Mother’s diet and nutrient Mother’s ability to mobilise and Uterine blood flow stores transport nutrients Placental structure and function Mother unable to supply nutrients to satisfy fetal demand FETAL UNDERNUTRITION Inadequate Adaptation to ‘building blocks’ reduce demand Kidneys Liver Pancreas Muscle, Brain HPA axis Fat, Bone Reduced nephron Altered zonation ↓ β cells ↓ Muscle and bone Appetite centres ↑ Cortisol numbers ↓ Insulin sensitivity ↓ Insulin secretion ↑ Fat Leptin resistance Early maturation ↓ IGF -1 ↓ Insulin sensitivity Central Insulin Hyperlipidaemia obesity resistance Hypertension Obesity and Type 2 diabetes Inactivity Coronary heart disease

In rats, maternal protein restriction in pregnancy: • Raised blood pressure, • Increased adiposity • Insulin resistance Maternal protein restriction • Glucose intolerance 40 35 Plasma 30 glucose 25 In the in adult 20 15 offspring Low protein adult offspring 10 (mmol/l) 5 Control 0 0 10 20 30 40 50 60 70 80 90 Time Hales & Ozanne. Biochem Soc Transac 1996;24:341-50

Maternal global diet restriction Vickers MH et al. Current Drug Targets 2007; 8: 923-34.

Birthweight and type 2 diabetes Overall Nurses Health Study Pima Indians 2.25 Odds Ratio for Type 2 1.75 Diabetes 1.25 .75 2 2.5 3 3.5 4 4.5 Birth Weight (kg) Whincup P et al. JAMA 2009

Low birth weight Diabetes

Insulin resistance (HOMA) 8-year-old children, Pune, India (n=477) Birthweight p=0.7 Current weight p<0.001 Birthweight p=0.03 Current weight p<0.001 1.7 Birthweight x 1.4 current weight p=0.004 1.1  22.8 ** 0.8 ns <22.8 <20 ns 0.5  2.5 -3.0 >3.0 *** ** ** Birthweight (kg) Bavdekar A et al. Diabetes 2000;48:2422-9

New Delhi: Childhood BMI of men and women who developed diabetes or pre-diabetes 230 out of 1518, aged 30 years BMI 0.5 SD score I GT/DM Cohort mean 0 -0.3 Bhargava et al 0 5 10 15 20 25 30 New Eng J Med Age (years) 2004;350:865-75

Pune Maternal Nutrition Study Women aged 814 Pregnancies Children now 15-40 yr in 6 Maternal diet 770 Newborns aged 15 years Body composition rural villages Blood nutrients Detailed Risk factors for N=2,466 (Fe, Fol, B12, C, D) anthropometry diabetes and Body Workload CHD measurements Fetal growth LMP dates

The ‘thin - fat’ newborn Yajnik CS et al. Int J Obesity 2003 Modi N et al. Ped Res 2009 van Steijn L et al. Int J Obesity 2009 Fall CHD. Ann Hum Biol 2011

Pune Maternal Nutrition Study Maternal nutrition and newborn size 3.0 p<0.001 Factors linked to small newborn Birthweight 2.5 (kg) size and/or the ‘thin - fat’ baby 2.0 Maternal stunting + adiposity 1.5 Foods: Green leafy vegetables Never <1 per >1 per every wk wk other day Fruit Green leafy vegetables @ 28 wks Milk 3.0 p<0.001 Blood nutrients: Folic acid Birthweight 2.5 Vitamin B12 (kg) Homocysteine 2.0 1.5 ≥ <357 <505 505 Rao S et al. J Nutr 2001;131:1217-24 Blood folate (nmol/l) @ 28 wks

Pune Maternal Nutrition Study Maternal nutrition and diabetes risk in the children Vitamin B12 @ 18 wks p=0.04 70% of women had low B12 Red cell folate @ 28 wks p<0.001 Only 1 had low folate Insulin 0.9 resistance 0.8 (HOMA) in the child 0.7 @ 6 years 0.6 0.5  505 <505 0.4 <357  160.0 <113.6 <160.0 18-week Vitamin B12 (pmol/l) Yajnik CS et al. Diabetologia 2008; 51: 29-38

Dutch Hunger Winter 1944-1945 Carbohydrates 3000 Fats 2800 2600 Protein 2400 Total number of calories 2200 2000 1800 1600 1400 1200 1000 800 600 400 200 Average monthly rations 0 II III IV I II III IV I II III IV I II III IV I II III IV 1941-1945 1941 1942 1943 1944 1945

Dutch Hunger Winter FAMINE BORN LATE MID EARLY CONCEIVED GEST N GEST N GEST N BEFORE AFTER EXPOSURE Maternal weight (kg) 66.7 61.8 63.5 67.9 69.1 Birthweight (g) 3372 3133 3217 3470 3413 Age 50 years SBP (mmHg) 126 127 125 123 125 LDL/HDL 2.9 2.8 2.7 3.3 2.9 120-min glucose (mmol/l) 5.7 6.3 6.1 6.1 5.9 Coronary heart disease % 4 3 1 9 3 IGT/diabetes % 15 21 14 16 15 Chronic airways dis % 16 15 25 23 17 ‘Poor health’ 5 6 4 10 5 Roseboom TJ Mol Cell Endocrinol 2001;185:93-98

INCAP trial, Guatemala 1969-1977 Cluster randomised by village; Pregnant/lactating women and children <7 years ATOLE Protein 6.4 g/100ml Energy 900 kcal/l FRESCO Energy 330 kcal/l Both supplements contained multiple micronutrients Stein AD et al. Am J Epidemiol 2006 164:1160-1170

INCAP trial Effects on risk factors at 25-42 years. Atole compared with Fresco FASTING GLUCOSE SYSTOLIC BLOOD TRIGLYCERIDES HDL CHOL (mg/dl) (mg/dl) PRESSURE (mm Hg) (mg/dl) Conception to 24 months (N= 257-332) Birth to 36 months (N=234-305) 24 to 48 months (N=263-359) 24 to 60 months (N=263-359) 36-72 months (N=198-277) 15 - 15 0 - 10 0 10 - 5 0 5 - 50 0 50 mg/dl mm Hg mg/dl mg/dl Stein AD et al. AM J Epidemiol 2006;164:1160-1170

ICDS supplements for mothers and children Hyderabad, adolescents aged 13-18 years (N=1165) Intervention Control Height (cm) 155.9 154.9 * BMI (kg/m2) 17.1 17.3 SBP (mmHg) 108.7 109.6 Arterial stiffness (%) 2.5 5.6 * LDL (mmol/l) 2.05 2.04 HDL (mmol/l) 0.99 1.00 Triglycerides (mmol/l) 0.82 0.83 Glucose (mmol/l) 4.68 4.72 HOMA 3.16 3.79 * Kinra S et al. BMJ 2008;337:a605

“ Minimat ” trial, Bangladesh Nutritional supplementation for mothers in pregnancy Children (N=1,335) studied at 4 years Food supplements Fe 30mg Fe 60mg Multiple from early pregnancy + + micronutrients (8-10 wks) Folic acid Folic acid Food supplements Fe 30mg Fe 60mg Multiple from mid-pregnancy + + micronutrients (17 wks) Folic acid Folic acid Early food supplementation: ↓glucose ↓ LDL cholesterol Multiple micronutrients: : ↓glucose ↓ insulin Lindstrom E et al. J DOHaD 2009;1 Suppl 1: S163

Multiple Micronutrient trial, Nepal Cluster randomised in early pregnancy, 1999-2001, N=4926 1. Vitamin A alone 2. Vit A + folate 3. Vit A + iron + folate 4. Vit A + iron + folate + zinc 5. Vit A + multiple micronutrients Children followed up at 6-8 years, N=3524 No differences in BP, glucose, insulin, lipids Iron+Folate+Zinc group had lower adiposity (skinfolds) Folate group had less Metabolic Syndrome Stewart CP et al. J Nutr 2009; 139: 1575-81

High-energy biscuit trial, Gambia Cluster randomised trial for 1460 women, 28 villages, 1989-1994 1015 kcal energy, 22g protein + micronutrients daily from ~20 wks gestation (during lactation in controls) Increased birth weight by 136 g (200 g hungry season) Reduced perinatal mortality Children followed up at 11-17 years, N=1267 Fasting glucose lower in intervention group -0.05 mmol/l ((5% CI -0.10 to -0.001) p=0.05 No differences in BP, body composition, lipids, insulin Hawkesworth S et al. AJCN 2011 (e-pub)