Nutrition 526 - 10/4/2002
Topics
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Pregnancy Data
Intergenerational Nutritional Effects
Fetal Growth and Chronic Disease
Public Health Approaches to Nutrition
and Pregnancy
Health, United States, 2002:
www.cdc.gov/nchs/hus.htm
• What does the pregnant/parenting
population look like?
• What have the trends been?
• Who’s not having babies?
Emerging Understandings
about Nutrition in Pregnancy:
• Fetal nutritional status is affected by the
intrauterine and childhood nutritional
experiences of the mother
• Maternal nutritional status at time of
conception is an important determinant of
outcomes
• Intrauterine nutritional environment affects
health and development of the fetus
throughout life
Emerging Understandings
about Nutrition in Pregnancy
• Periods of critical development are key when
considering effects of nutrition in pregnancy.
Undernutrition has different effects at different times
of life.
• Societies transitioning from chronic malnutrition to
access to high calorie foods are at high risk of
chronic disease due to lasting effects of early
nutritional status
Emerging Understandings
about Nutrition in Pregnancy
(Coming Attractions….)
• Pregnancy is a period of increased flexibility
in metabolism and absorption of energy and
nutrients.
Effect of Women’s own
Intrauterine Nutritional
Experience her Offspring
Two Studies of Effects of
Maternal Birthweight on Infant
Birthweight
Godfrey KM, Barker DJP, Robinson S, Osmond C.
Mother's birthweight and diet in pregnancy in relation to
the baby's thinness at birth. Br J Obstet Gynaecol
1997;104:663–7
Illinois Study
Coutinho et al. Am J Epi, 1997 146:804-809
• N=15,287 Black and 117,708 white
matched pairs of infants and mothers.
• Mothers were born between 1956-75,
infants between 1989-1991
Mean infant
birthweight
Mean parental
birthweight
% low birthweight
infants
% lbw born to
women with lbw
% lbw born to
women not lbw
Black
White
3139 g
3434
3133
3377
12%
5%
18%
9%
11%
5%
Results
• Father’s birthweight had effect on infant
birthweight but not as strong as mothers.
• In multiple linear regression for infants who
weighed more than 2500 g, parental
birthweight accounted for 5% of variance
among black infants and 4% among white
infants.
• (included parental age, years of schooling,
matiral status and adequacy of prenatal care)
Results, cont.
• Each 100 g increase in maternal
birthweight was associated with 24-27 g
increase in infant birthweight
Influence of Maternal
Intrauterine & Childhood
Nutrition on Outcomes of
Pregnancy
Reproductive performance and
nutrition during childhood
Nutrition Reviews; Washington; Apr
1996; Martorell, Reynaldo;
Ramakrishnan, Usha; Schroeder, Dirk
G; Ruel, Marie;
Longitudinal Supplementation
Trial (1969-1977)
• Guatemala, 4 Villages, one pair of villages
had about 900 people each and the other
about 500 each.
• 2 each randomized to:
• Atole (Incaparina, a vegetable protein mix
developed by INCAP*, dry skim milk, sugar,
and flavoring, 163 kcal/cup, 11/5 g protein)
• Fresco (flavored drink with sugar, vitamins
and minerals, 59 kcal/cup)
*Institute of Nutrition of Central America and Panama
• Feeding center was open daily for over 7 years, from
1969 to 1977.
• Anyone in the village could attend, but careful
recording of consumption, including of additional
servings as well as of leftovers, was done only for
women who were pregnant or breastfeeding and for
children 7 years or younger.
• Supplements were available twice daily, in
midmorning and midafternoon, so as not to interfere
with meal times.
Conceptual framework
“Malnutrition in early childhood constrains
the future capacity of women to bear
healthy newborns and their ability to feed
and care for them, and through these
mechanisms the growth and development of
the next generation.”
Follow-Up data - 1990s
• The prevalence of low birthweight is
currently 12% in Atole villages (n = 65) and
28% in Fresco villages (n = 58) among
women exposed to the supplements during
the intrauterine period and the first 3 years
of life.
• Mean birthweights are 2.90 kg in Atole
villages and 2.73 in Fresco villages.
Role of intergenerational
effects on linear growth
U Ramakrishnan; R Martorell; D G
Schroeder; R Flores; The Journal
of Nutrition; Bethesda; Feb 1999;
Methods
• The sample was restricted to singleton, term
(>37 wk of gestation) births that occurred in
the four study villages between 1991 and
1996, to women who were born during the
original longitudinal study (1969-1977)
• Complete data were available for 215 motherchild pairs, and 60% of the mothers (n = 140)
Results
• For every 100 g increase in maternal birth
weight, her infant's birth weight increased by
29 g after adjusting for the effects of maternal
age, gestational age and sex of the infant.
This relationship was highly significant (P <
0.001)
• For every centimeter increase in maternal
birth length, her child's birth weight increased
by 53 g.
Influence of Maternal Nutrition
in Pregnancy
Dutch Famine Studies
Susser and Stein, Nutrition Reviews, 1994
• Dutch famine winter lasted 6 months,
from November 1944- when nazis
imposed transport embargo on west
Holland until• May 7, 1945 when Holland was
liberated from the occupation
• Strong evidence for critical stages of
development in several physiological
systems
Affects of Famine
• Fertility decreased
• Maternal weight fell during pregnancy
with famine exposure
• Third trimester famine exposure had
strong effect on birthweight
• Third trimester famine exposure was
associated with infant mortality at 30-90
days
Results for Infants Exposed to
Famine
• Excess central nervous system disorders
(such as NTD)
• Exposure early in gestation associated with
excess obesity in young men (military
records) and women
• Famine exposure late in pregancy associated
with less obesity in young adulthood
• Famine exposure associated with twofold risk
of schizophrenia in 50 year old women.
Second Generation
• Modest association found in this cohort
between birthweights of mothers and
their offspring.
Prenatal exposure to famine and
brain morphology in schizophrenia
Hulshoff Pol HE; Hoek HW; Susser E; Brown AS;
Dingemans A; Schnack HG; van Haren NE; Pereira
Ramos LM; Gispen-de Wied CC; Kahn RS; American
Journal of Psychiatry , Jul 2000;
Methods
• Nine schizophrenic patients and nine
healthy comparison subjects exposed
during the first trimester of gestation to
the Dutch Hunger Winter were
evaluated with magnetic resonance
brain imaging, as were nine
schizophrenic patients and nine healthy
subjects who were not prenatally
exposed to the famine.
RESULTS:
• Prenatal famine exposure in patients
with schizophrenia was associated with
decreased intracranial volume.
• Prenatal Hunger Winter exposure alone
was related to an increase in brain
abnormalities, predominantly white
matter hyperintensities.
Further evidence of relation
between prenatal famine and
major affective disorder.
Alan S Brown; Jim van Os;
Corine Driessens; Hans W Hoek;
et al; The American Journal of
Psychiatry; Washington; Feb
2000;
Methods
• Compared the risk of major affective
disorder requiring hospitalization in birth
cohorts who were and were not
exposed, in each trimester of gestation,
to famine during the Dutch Hunger
Winter of 1944-1945.
Results
• The risk of developing major affective
disorder requiring hospitalization was
increased for subjects with exposure to
famine in the second trimester and was
increased significantly for subjects with
exposure in the third trimester, relative
to unexposed subjects.
Fetal Nutrition and Chronic
Diseases of Adulthood
Fetal Origins Concepts
Barker et al
• Nutrition in early life has permanent
effects
• Undernutrition has different effects at
different times of life.
• Rapidly growing fetuses and neonates
are vulnerable to undernutrition
• Undernutrition results from inadequate
maternal intake, transport, or transfer of
nutrients.
Coronary heart disease death rates, expressed
as standardized mortality ratios, in 10,141
men and 5585 women born in Hertfordshire,
United Kingdom, from 1911 to 1930,
according to birth weight.
(Osmond C, Barker DJP, Winter PD, Fall
CHD, Simmonds SJ. Early growth and death
from cardiovascular disease in women. BMJ
1993;307:1519–24)
Catch-up growth in childhood and death
from coronary heart disease: longitudinal
study (Eriksson et al, BMJ, 1999)
• Subjects: 3641 men born in Helsinki
between 1924-1933
• Followed with school data for weight
and height
• Deaths from coronary heart disease
from 1971-95 (standardized mortality
ratios) were endpoints.
Catch-up growth in childhood and death
from coronary heart disease: longitudinal
study (Eriksson et al, BMJ, 1999
• Men who had low birth weight or were thin at
birth have high death rates from coronary
heart disease
• Death rates are even higher if weight
"catches up" in early childhood
• Death from coronary heart disease may be a
consequence of prenatal undernutrition
followed by improved postnatal nutrition
• Programs to reduce obesity among boys may
need to focus on those who had low birth
weight or who were thin at birth
Framework for understanding the maternal
regulation of fetal development and
programming. Keith M Godfrey and David
JP Barker
(Fetal nutrition and adult disease
Am J Clin Nutr 2000 71: 1344-1352)
Early Nutrition & Chronic Disease in
Adulthood (Waterland& Garza, Am J Clin Nutr, 1999;69:179-97)
• Epi studies: BMI, CVD, Htn, IGT
• Animal studies
• Potential mechanisms of metabolic
imprinting
Obesity in Young Men after Famine
Exposure in Utero and early Infancy
(Ravelli et al NEJM, 1976)
• N=300, 000 Dutch military inductees at age
19
• Famine exposure in first 2 trimesters lead to
80% higher prevalence of overweight
(p<0.0005)
• Famine exposure in last trimester or famine
exposure in first 5 months of life associated
with 40% lower prevalence of overweight
(p<0.005)
BMI
• The relationship between birth weight
and BMI complicates studies of birth
weight and chronic disease
Preadult Influences on Cardiovascular Disease
and Cancer (Leon & Ben-Shlomo in A Lifecourse approach to
chronic disease epidemiology, 1997)
• 5 large retrospective studies - 4 found
inverse relationship between birth
weight and adult CVD
• Confounding issues include SES and
BMI
CVD
“The preponderance of data suggest an
inverse association between birth
weight and adult CVD risk.” (Waterland and
Garza)
Blood Pressure
“Retrospective studies in diverse
populations have found that birth weight
is inversely correlated with adult blood
pressure. Although each of the studies
has some weaknesses, together they
support a biological link between
intrauterine growth and adult blood
pressure” (Waterland and Garza)
Impaired Glucose Tolerance
• Several large retrospective cohort
studies in several countries have found
relationship between bw and IGT.
• 266 men and women at age 50: odds
ratio for ITG or type II diabetes were 3.5
for men and 12 for women with birth
weights < 2.5 compared to >3.4 (Phillips et al,
Diabetologia, 1994)
Impaired Glucose Tolerance,
cont..
• In some populations (ex: Pima Indians)
both high and low birth weights are
associated with IGT in adults.
Animal Models (Waterland and Garza)
“Overall the data from animal models of
metabolic imprinting support the
observed epidemiological associations.”
Metabolic Imprinting
“…the basic biological phenomena that
putatively underlie relations among
nutritional experiences of early life and
later diseases.”
Metabolic Imprinting:
Characteristics
• Susceptibility limited to a critical
ontogenic window early in development
• Persistent effect lasting through
adulthood
• Specific and measurable outcome
• Dose-response or threshold relation
between exposure and outcome
Metabolic Imprinting:
Potential Mechanisms
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Organ structure
Cell number
Clonal selection
Metabolic differentiation
Organ Structure
• Organogenesis starts early: by 5 weeks
rudimentary organs are in place, by 8
weeks organogenesis is nearly
complete
• Driven by inductive signals from
adjacent cells and morphogen gradients
(ex: retinoic acid/vit. A)
• Local concentrations of nutrients and
metabolites may modulate this process.
Cell Number
• Tissues go through limited periods of
hyperplastic and hypertrophic growth
• Rate of growth is dependent on nutrient
availability
• Winnick’s rat studies found severe
malnutrition during critical periods limited
brain cell number
• An organ’s metabolic activity is limited by cell
number
Clonal Selection
• Each organ is based on a finite number of
founder cells which may have slight
differences
• Founder cells that divide the most rapidly
may disproportionally make up a tissue
• Nutrient availability may “select” cells with
certain characteristics
• Ex: cells with more active lipogenic pathways
could grow faster if access to fatty acids was
limited
Metabolic Differentiation
• Process: cells develop stable patterns
of basal and inducible gene expression
• Cells are characterized by the ability to
express a limited number of genes.
• Mechanisms of control include:
– chromatin structure (DNA “packaging”)
– transcription factors (maintained through cell
divisions)
– DNA methylation
Metabolic Imprinting:
• Early nutrition may influence the
cascade that establishes cell specific
patterns.
• Ex: hepatocyte polyploidization - in
adults hepatocytes often have > normal
complement of chromosomes and
increased metabolic activity. Lack of
polyploidization could limit hepatic
metabolic activity.
Catch-up growth in childhood and death
from coronary heart disease: longitudinal
study (Eriksson et al, BMJ, 1999)
• Subjects: 3641 men born in Helsinki
between 1924-1933
• Followed with school data for weight
and height
• Deaths from coronary heart disease
from 1971-95 (standardized mortality
ratios) were endpoints.
Catch-up growth in childhood and death
from coronary heart disease: longitudinal
study
(Eriksson et al, BMJ, 1999
• Men who had low birth weight or were thin at
birth have high death rates from coronary
heart disease
• Death rates are even higher if weight
"catches up" in early childhood
• Death from coronary heart disease may be a
consequence of prenatal undernutrition
followed by improved postnatal nutrition
• Programs to reduce obesity among boys may
need to focus on those who had low birth
weight or who were thin at birth
Public Health Approaches to
Nutrition and Pregnancy
Highlights of Trends in Pregnancies
and Pregnancy Rates by Outcome:
Estimates for the United States,
1976-96
Ventura et al., National Vital
Statistics Reports. 47:29, 1999.
Basic US Data
• In 1996 there were:
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6.24 million pregnancies
3.89 live births
1.37 induced abortions
0.98 fetal losses
• 1996 pregnancy rate was 104.7
pregnancies per 1000 women aged
15044 - 9% lower than 1990
Effects of pregnancy planning status
on birth outcomes and infant care (Kost
et al. Family Planning Perspectives, 1998)
• Analysis of 1988 NMIHS (n=9122) and
NSFG (n=2548) data.
Effects of pregnancy planning status
on birth outcomes and infant care (Kost
et al. Family Planning Perspectives, 1998)
Intended
Mistimed Unwanted
LBW
5.1
6.5
9.7
SGA
9.5
11.3
13.7
20.4
25.5
46.6
36.1
Any
15.6
negative
outcomes
Ever
59.9
breastfed
Effects of pregnancy planning status
on birth outcomes and infant care (Kost
et al. Family Planning Perspectives, 1998)
• “Knowing the planning status of a
pregnancy can help identify women who
may need support to engage in prenatal
behaviors that are associated with
healthy outcomes and appropriate infant
care.”
Surveillance for Pregnancy
• PRAMS results
Healthy People 2010 Goals
Related to Maternal and Infant
& Nutrition
Reduce low birth weight (LBW) and
very low birth weight (VLBW).
Reduction in Low and
Very Low Birth Weight
Low birth weight (LBW)
Very low birth weight
(VLBW)
1998
Baseline
Percent
7.6
1.4
2010
Target
5.0
0.9
Reduce preterm births
Reduction in
Preterm Births
1997
Baseline (%)
2010
Target (%)
Total preterm
11.4
7.6
Live births at 32 to 36
weeks of gestation
9.4
6.4
Live births at less
than 32 weeks of
gestation
1.9
1.1
Increase the proportion of mothers who
achieve a recommended weight gain during
their pregnancies. (Developmental)
• In 1988, approximately three-quarters of
married women who delivered at full term
gained the recommended weight during
pregnancy.71 Two groups of women who
continue to gain less than the recommended
level of weight during pregnancy—teenagers
and African American women—also are at
particularly high risk for having LBW infants
and other adverse pregnancy outcomes
Reduce the occurrence of spina bifida
and other neural tube defects (NTDs)
• Target: 3 new cases per 10,000 live births.
• Baseline: 6 new cases of spina bifida or
another NTD per 10,000 live births in 1996.
Increase the proportion of pregnancies
begun with an optimum folic acid level.
Increase in Pregnancies
Begun With Optimum
Folic Acid Level
1991–94
Baseline*
2010
Target
Consumption of at least
400 μg of folic acid each
day from fortified foods or
dietary supplements by
nonpregnant women aged
15 to 44 years
21%
80%
161 ng/ml
220 ng/ml
Median RBC folate level
among nonpregnant
women aged 15 to 44
years
Increase abstinence from alcohol,
cigarettes, and illicit drugs among
pregnant women
1996–97
Baseline %
2010
Target %
86
94
Binge drinking
99
100
Cigarette smoking†
87
98
Illicit drugs
98
100
Increase in Reported
Abstinence in Past
Month From
Substances by
Pregnant Women*
Alcohol
Reduce the occurrence of fetal alcohol
syndrome(FAS).(Developmental)
• Estimates of the cases of FAS vary from
0.2 to 1.0 per 1,000 live births.
Increase the proportion of mothers
who breastfeed their babies
Increase in Mothers
Who Breastfeed
1998
Baseline (%)
2010
Target (%)
In early postpartum
period
64
75
At 6 months
29
50
At 1 year
16
25
Increase smoking cessation during
pregnancy
• Target: 30 percent.
• Baseline: 12 percent smoking cessation
during the first trimester of pregnancy in 1991
(age adjusted to the year 2000 standard
population).
Reduce growth retardation among low
income children under age 5 years
• Target: 5 percent.
• Baseline: 8 percent of low-income children
under age 5 years were growth retarded in
1997 (defined as height-for-age below the
fifth percentile in the age-gender appropriate
population using the 1977 NCHS/CDC growth
charts;31 preliminary data; not age adjusted).
Reduce iron deficiency among young
children and females of childbearing age.
1988–94
Baseline (%)
2010
Target (%)
Children aged 1 to 2
years
9
5
Children aged 3 to 4
years
4
1
Nonpregnant females
aged 12 to 49 years
11
7
Reduction in Iron
Deficiency*
Reduce anemia among low-income
pregnant females in their third trimester
• Target: 20 percent.
• Baseline: 29 percent of low-income
pregnant females in their third trimester
were anemic (defined as hemoglobin <
11.0 g/dL) in 1996
Anemia Rates - 1996
African American, non-Hispanic
American Indian/Alaska Native
Asian/Pacific Islander
Hispanic
White, non-Hispanic
44%
31%
26%
25%
24%
Reduce iron deficiency among
pregnant females (Developmental)
• Although the prevalence of iron
deficiency among low-income children
continued to decline from 1976-80 to
1988-94, the prevalence of iron
deficiency among all young children
remained the same, and the prevalence
of iron deficiency among females of
childbearing age actually increased