Tessa J. Roseboom

Birth weight and risk of type 2 diabetes: A systematic review

CONTEXT Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined. OBJECTIVE To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults. DATA SOURCES AND STUDY SELECTION Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included. DATA EXTRACTION Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations. DATA SYNTHESIS Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight-type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I(2) = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight-type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of publication or small study bias. CONCLUSION In most populations studied, birth weight was inversely related to type 2 diabetes risk.

Effects of interventions in pregnancy on maternal weight and obstetric outcomes: meta-analysis of randomised evidence

Objective To evaluate the effects of dietary and lifestyle interventions in pregnancy on maternal and fetal weight and to quantify the effects of these interventions on obstetric outcomes. Design Systematic review and meta-analysis. Data sources Major databases from inception to January 2012 without language restrictions. Study selection Randomised controlled trials that evaluated any dietary or lifestyle interventions with potential to influence maternal weight during pregnancy and outcomes of pregnancy. Data synthesis Results summarised as relative risks for dichotomous data and mean differences for continuous data. Results We identified 44 relevant randomised controlled trials (7278 women) evaluating three categories of interventions: diet, physical activity, and a mixed approach. Overall, there was 1.42 kg reduction (95% confidence interval 0.95 to 1.89 kg) in gestational weight gain with any intervention compared with control. With all interventions combined, there were no significant differences in birth weight (mean difference −50 g, −100 to 0 g) and the incidence of large for gestational age (relative risk 0.85, 0.66 to 1.09) or small for gestational age (1.00, 0.78 to 1.28) babies between the groups, though by itself physical activity was associated with reduced birth weight (mean difference −60 g, −120 to −10 g). Interventions were associated with a reduced the risk of pre-eclampsia (0.74, 0.60 to 0.92) and shoulder dystocia (0.39, 0.22 to 0.70), with no significant effect on other critically important outcomes. Dietary intervention resulted in the largest reduction in maternal gestational weight gain (3.84 kg, 2.45 to 5.22 kg), with improved pregnancy outcomes compared with other interventions. The overall evidence rating was low to very low for important outcomes such as pre-eclampsia, gestational diabetes, gestational hypertension, and preterm delivery. Conclusions Dietary and lifestyle interventions in pregnancy can reduce maternal gestational weight gain and improve outcomes for both mother and baby. Among the interventions, those based on diet are the most effective and are associated with reductions in maternal gestational weight gain and improved obstetric outcomes.

Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life

Objective  Maternal undernutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. We investigated whether these effects may persist in subsequent generations.

Hungry in the womb: what are the consequences? Lessons from the Dutch famine.

An increasing body of evidence suggests that poor nutrition at the very beginning of life - even before birth - leads to large and long term negative consequences for both mental and physical health. This paper reviews the evidence from studies on the Dutch famine, which investigated the effects of prenatal undernutrition on later health. The effects of famine appeared to depend on its timing during gestation, and the organs and tissues undergoing critical periods of development at that time. Early gestation appeared to be the most vulnerable period. People who were conceived during the famine were at increased risk of schizophrenia and depression, they had a more atherogenic plasma lipid profile, were more responsive to stress and had a doubled rate of coronary heart disease. Also, they performed worse on cognitive tasks which may be a sign of accelerated ageing. People exposed during any period of gestation had more type 2 diabetes. Future investigation will expand on the finding that the effects of prenatal famine exposure may reach down across generations, possibly through epigenetic mechanisms. Recent evidence suggests that similar effects of prenatal undernutrition are found in Africa, where many are undernourished. Hunger is a major problem worldwide with one in seven inhabitants of this planet suffering from lack of food. Adequately feeding women before and during pregnancy may be a promising strategy in preventing chronic diseases worldwide.

Prenatal undernutrition and cognitive function in late adulthood

At the end of World War II, a severe 5-mo famine struck the cities in the western part of The Netherlands. At its peak, the rations dropped to as low as 400 calories per day. In 1972, cognitive performance in 19-y-old male conscripts was reported not to have been affected by exposure to the famine before birth. In the present study, we show that cognitive function in later life does seem affected by prenatal undernutrition. We found that at age 56 to 59, men and women exposed to famine during the early stage of gestation performed worse on a selective attention task, a cognitive ability that usually declines with increasing age. We hypothesize that this decline may be an early manifestation of an accelerated cognitive aging process.

Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview

Chronic diseases are the main public health problem in Western countries. There are indications that these diseases originate in the womb. It is thought that undernutrition of the fetus during critical periods of development would lead to adaptations in the structure and physiology of the fetal body, and thereby increase the risk of diseases in later life. The Dutch famine--though a historical disaster--provides a unique opportunity to study effects of undernutrition during gestation in humans. This thesis describes the effects of prenatal exposure to the Dutch famine on health in later life. We found indications that undernutrition during gestation affects health in later life. The effects on undernutrition, however, depend upon its timing during gestation and the organs and systems developing during that critical time window. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. Little is known about what an adequate diet for pregnant women might be. In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations.

Transgenerational effects of prenatal exposure to the 1944–45 Dutch famine

We previously showed that maternal under‐nutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. Also, we found increased neonatal adiposity among the grandchildren of women who had been undernourished during pregnancy. In the present study we investigated whether these transgenerational effects have led to altered body composition and poorer health in adulthood in the grandchildren.

Prenatal exposure to the Dutch famine is associated with a preference for fatty foods and a more atherogenic lipid profile

BACKGROUND Evidence from animal models suggests that fetal undernutrition can predispose to hypercholesterolemia and metabolic disorders directly by programming cholesterol metabolism and may indirectly influence lifestyle choices. We have shown that persons who were exposed to the Dutch famine in early gestation have a more atherogenic lipid profile. OBJECTIVE We now investigate whether the excess in hypercholesterolemia may be a result of a more atherogenic diet or a reduction in physical activity. DESIGN We measured lipid profiles, dietary intake, and physical activity in 730 men and women (aged 58 y) born in the Wilhelmina Gasthuis in Amsterdam, Netherlands, around the time of the Dutch famine, whose birth records have been kept. RESULTS No differences were observed in mean intake of total energy or percentage of protein, carbohydrate, and fat in the diet between the different exposure groups. However, persons exposed to famine in early gestation were twice as likely (odds ratio: 2.1; 95% CI: 1.2, 3.9) to consume a high-fat diet (defined as the highest quartile of percentage of fat in the diet: >39% of energy from fat). They also tended to be less physically active (45% did sports compared with 52% in the unexposed group), although this did not reach statistical significance. CONCLUSIONS This is the first direct evidence in humans that prenatal nutrition may affect dietary preferences and may contribute to more atherogenic lipid profiles in later life.

Microalbuminuria in Adults after Prenatal Exposure to the Dutch Famine

Maternal undernutrition during gestation is associated with an increase in cardiovascular risk factors in the offspring in adult life. The effect of famine exposure during different stages of gestation on adult microalbuminuria (MA) was studied. MA was measured in 724 people, aged 48 to 53, who were born as term singletons in a university hospital in Amsterdam, the Netherlands, around the time of the Dutch famine 1944 to 1945. Twelve percent of people who were exposed to famine in mid gestation had MA (defined as albumin/creatinine ratio >/=2.5) compared with 7% of those who were not prenatally exposed to famine (odds ratio 2.1; 95% confidence interval 1.0 to 4.3). Correcting for BP, diabetes, and other influences that affect MA did not attenuate this association (adjusted odds ratio 3.2; 95% confidence interval 1.4 to 7.7). The effect of famine was independent of size at birth. Midgestation is a period of rapid increase in nephron number, which is critical in determining nephron endowment at birth. Fetal undernutrition may lead to lower nephron endowment with consequent MA in adult life.

Interventions to Reduce or Prevent Obesity in Pregnant Women: A Systematic Review

BACKGROUND Around 50% of women of childbearing age are either overweight [body mass index (BMI) 25-29.9 kg/m(2)] or obese (BMI ≥ 30 kg/m(2)). The antenatal period provides an opportunity to manage weight in pregnancy. This has the potential to reduce maternal and fetal complications associated with excess weight gain and obesity. OBJECTIVES To evaluate the effectiveness of dietary and lifestyle interventions in reducing or preventing obesity in pregnancy and to assess the beneficial and adverse effects of the interventions on obstetric, fetal and neonatal outcomes. DATA SOURCES Major electronic databases including MEDLINE, EMBASE, BIOSIS and Science Citation Index were searched (1950 until March 2011) to identify relevant citations. Language restrictions were not applied. REVIEW METHODS Systematic reviews of the effectiveness and harm of the interventions were carried out using a methodology in line with current recommendations. Studies that evaluated any dietary, physical activity or mixed approach intervention with the potential to influence weight change in pregnancy were included. The quality of the studies was assessed using accepted contemporary standards. Results were summarised as pooled relative risks (RRs) with 95% confidence intervals (CIs) for dichotomous data. Continuous data were summarised as mean difference (MD) with standard deviation. The quality of the overall evidence synthesised for each outcome was summarised using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology and reported graphically as a two-dimensional chart. RESULTS A total of 88 studies (40 randomised and 48 non-randomised and observational studies, involving 182,139 women) evaluated the effect of weight management interventions in pregnancy on maternal and fetal outcomes. Twenty-six studies involving 468,858 women reported the adverse effect of the interventions. Meta-analysis of 30 RCTs (4503 women) showed a reduction in weight gain in the intervention group of 0.97 kg compared with the control group (95% CI -1.60 kg to -0.34 kg; p = 0.003). Weight management interventions overall in pregnancy resulted in a significant reduction in the incidence of pre-eclampsia (RR 0.74, 95% CI 0.59 to 0.92; p = 0.008) and shoulder dystocia (RR 0.39, 95% CI 0.22 to 0.70; p = 0.02). Dietary interventions in pregnancy resulted in a significant decrease in the risk of pre-eclampsia (RR 0.67, 95% CI 0.53 to 0.85; p = 0.0009), gestational hypertension (RR 0.30, 95% CI 0.10 to 0.88; p = 0.03) and preterm birth (RR 0.68, 95% CI 0.48 to 0.96; p = 0.03) and showed a trend in reducing the incidence of gestational diabetes (RR 0.52, 95% CI 0.27 to 1.03). There were no differences in the incidence of small-for-gestational-age infants between the groups (RR 0.99, 95% CI 0.76 to 1.29). There were no significant maternal or fetal adverse effects observed for the interventions in the included trials. The overall strength of evidence for weight gain in pregnancy and birthweight was moderate for all interventions considered together. There was high-quality evidence for small-for-gestational-age infants as an outcome. The quality of evidence for all interventions on pregnancy outcomes was very low to moderate. The quality of evidence for all adverse outcomes was very low. LIMITATIONS The included studies varied in the reporting of population, intensity, type and frequency of intervention and patient complience, limiting the interpretation of the findings. There was significant heterogeneity for the beneficial effect of diet on gestational weight gain. CONCLUSIONS Interventions in pregnancy to manage weight result in a significant reduction in weight gain in pregnancy (evidence quality was moderate). Dietary interventions are the most effective type of intervention in pregnancy in reducing gestational weight gain and the risks of pre-eclampsia, gestational hypertension and shoulder dystocia. There is no evidence of harm as a result of the dietary and physical activity-based interventions in pregnancy. Individual patient data meta-analysis is needed to provide robust evidence on the differential effect of intervention in various groups based on BMI, age, parity, socioeconomic status and medical conditions in pregnancy.