1. Nutrition 526 - 9/29/2006 A Public Health Approach to Maternal and Infant Health

2. Topics
Who is having babies in the US? How many babies? What are the outcomes?
Why is nutrition important for pregnant women and babies?
What population based approaches to improve nutrition might improve outcomes?

3. Topic 1 How many babies? Who is having babies in the US?
Race/ethnicity
Age
Marital status
What are the nutrition-related outcomes we are concerned about for population health?

4. Health, United States, 2005: www.cdc.gov/nchs/hus.htm

14. Percentage of Parents Who Were Married or Cohabiting
at Birth of First Child, by Race/Ethnicity and Sex
MMWR; September 15, 2006 / 55(36);998

15. Infant Mortality
Infant mortality rate – Deaths of infants aged under 1 year per 1,000 or 100,000 live births. The infant mortality rate is the sum of the neonatal and postneonatal mortality rates.
Neonatal mortality rate – Deaths of infants aged 0-27 days per 1,000 live births. The neonatal mortality rate is the sum of the early neonatal and late neonatal mortality rates
Postneonatal mortality rate – Deaths to infants aged 28 days-1 year per 1,000 live births.

17. Infant Deaths Per Thousand Live Births, by Race and Hispanic Origin 1960-1995 
National Center for Health Statistics. Health, United States, 1995

18. Racial/Ethnic Disparities in Infant Mortality --- United States, 1995--2002
MMWR; June 10, 2005 / 54(22);

19. MMWR, April 19, 2002 / 51(15); , 343

20. Supplemental Analyses of Recent Trends in Infant Mortality, CDC
Figure 2.  Rates of infant mortality, low birthweight, and preterm birth,
Supplemental Analyses of Recent Trends in Infant Mortality, CDC
February 11, 2004

21. Health Affairs, Vol 23, Issue 5, 2004

22. Causes of Infant Death

24. Health Affairs, Vol 23, Issue 5, 2004

25. Rates of Premature Birth (%) Rates Infant Morality(%)
Rates of LBW (%)
Rates of Premature Birth (%)
Rates Infant Morality(%)
African Americans
13.4
17.7
13.5
Asians
7.8
10.4
4.6
Native Americans
7.2 13
9.7
Whites
6.9 11
5.7
Hispanics
6.5
11.6
5.4
NGA Center for Best Practices, June 2004

26. Reported Stressful Life Events During Year Before Delivery King County, Pregnancy Risk Assessment Monitoring System (PRAMS)

27. Argued with partner more than usual 36%* 43%* 17%
African Amer.
Amer. Indian/AK Native
White
Changed residence
44%*
53%*
33%
Argued with partner more than usual
36%*
43%*
17%
Had bills couldn’t pay
31%*
42%*
14%
Someone close died
24%*
25%
15%
Close family member hospitalized
24%
22%
Separated or divorced from partner
20%*
19%* 5%
Someone close had drinking/drug problem
28%*
13%
Partner said he didn’t want pregnancy
15%*
21%* 8%
Husband/partner lost job
Mom or partner went to jail
10%
22%* 4%
Involved in a physical fight 7%
12%*
Homeless
11%* 1%
Reported 5 or more stress events
23%*
* stat. sig compared to whites

28. Maternal Mortality

29. African American and White Women Who Died of Pregnancy Complications,
African American and White Women Who Died of Pregnancy Complications,* United States
* Annual number of deaths during pregnancy or within 42 days after delivery, per 100,000 live births. † The apparent increase in the number of maternal deaths between 1998 and 1999 is the result of changes in how maternal deaths are classified and coded. Source: CDC, National Center for Health Statistics.

30. Risk of Maternal Death Race/ethnicity Age
The risk of death for African American women is almost four times that for white women.
The risk of death for Asian and Pacific Islander women who immigrated to the United States is two times that for Asian and Pacific Islander women born in the United States.
Age
The risk of death is nearly three times greater for women 35–39 years old than for women 20–24 years old.
The risk is five times greater for women over 40.

31. The most common serious pregnancy complications
Ectopic pregnancy
Depression
High blood pressure
Infection
Complicated delivery
Diabetes
Premature labor
Hemorrhage

32. Topic 2
Why is nutrition important for pregnant women and babies?

33. Poor Pregnancy Outcomes are Costly
Medicaid finances 40% of annual births in the US and pays for 50% of hospital stays for premature and LBW.
The care cost for children with one of 17 common birth defects is $8 billion per year in the US.

34. Improve access to medical care and health care services
Top Three “Best Practices” to Improve Birth Outcomes and Reduce High Risk Births (NGA, June 2004)
Improve access to medical care and health care services
Encourage good nutrition and healthy lifestyles
Eating healthy foods
Taking folic acid
Reduce use of harmful substances

35. 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

36. 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.

37. Effect of Women’s own Intrauterine Nutritional Experience her Offspring

38. Two Studies of Effects of Maternal Birthweight on Infant Birthweight

39. Classic Definitions of Birth weight
Extremely low birth weight (ELBW)
< 1000 g
Very low birth weight (VLBW)
<1500 g
Moderately Low birth weight
1500 to <2500 g
Low birth weight
<2500 g (HP2010)
Normal (NBW)
2500-<4000 g
Ideal birth weight
3500- <4000g
High birth weight (HBW)
>4000 g

40. Godfrey KM, Barker DJP, Robinson S, Osmond C
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 ;104:663–7

42. 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 , infants between

44. 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.
(adjusted for parental age, years of schooling, marital status and adequacy of prenatal care)

45. Results, cont.
Each 100 g increase in maternal birthweight was associated with g increase in infant birthweight

46. Influence of Maternal Intrauterine & Childhood Nutrition on Outcomes of Pregnancy

47. Reproductive performance and nutrition during childhood
Nutrition Reviews; Washington; Apr 1996; Martorell, Reynaldo; Ramakrishnan, Usha; Schroeder, Dirk G; Ruel, Marie;

48. 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

49. 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.

50. 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.”

56. Follow-Up data s
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.

57. Role of intergenerational effects on linear growth
U Ramakrishnan; R Martorell; D G
Schroeder; R Flores; The Journal of Nutrition; Bethesda; Feb 1999;

58. 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 ( )
Complete data were available for 215 mother-child pairs, and 60% of the mothers (n = 140)

59. 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.

60. Influence of Maternal Nutrition in Pregnancy

61. Dutch Famine Studies Susser and Stein, Nutrition Reviews, 1994
Dutch famine winter lasted 6 months, from November 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

62. 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 days

64. 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.

65. Second Generation
Modest association found in this cohort between birthweights of mothers and their offspring.

66. 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;

67. 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.

68. 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.

69. 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;

70. 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

71. 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.

72. Fetal Nutrition and Chronic Diseases of Adulthood

73. Fetal Origins Concepts Barker et al
Nutrition in early life has permanent effects on structure, physiology and metabolism
Undernutrition has different effects at different times of life (critical periods of development)
Rapidly growing fetuses and neonates are vulnerable to undernutrition
Undernutrition results from inadequate maternal intake, transport, or transfer of nutrients.

74. 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)

76. Catch-up growth in childhood and death from coronary heart disease: longitudinal study (Eriksson et al, BMJ, 1999)
Subjects: men born in Helsinki between
Followed with school data for weight and height
Deaths from coronary heart disease from (standardized mortality ratios) were endpoints.

78. 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

79. 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 : )

81. 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

82. 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)

83. BMI
The relationship between birth weight and BMI complicates studies of birth weight and chronic disease

84. Confounding issues include SES and BMI
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

85. CVD
“The preponderance of data suggest an inverse association between birth weight and adult CVD risk.” (Waterland and Garza)

86. 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)

87. 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)

88. Impaired Glucose Tolerance, cont..
In some populations (ex: Pima Indians) both high and low birth weights are associated with IGT in adults.

89. Animal Models (Waterland and Garza)
“Overall the data from animal models of metabolic imprinting support the observed epidemiological associations.”

90. Epigenetics
Epigenetics = the study of stable alterations in gene expression that arise during development and cell proliferation Epigenetic phenomena do NOT change the actual, primary genetic sequence
Epigenetic phenomena are important because, together with promotor sequences and transcription factors, they modulate when and at what level genes are expressed
The protein context of a cell can be understood as an epigenetic phenomena.
Examples include: DNA methylation, histone hypo-acetylation, chromatin modifications, X-inactivation, and imprinting.

91. Metabolic Imprinting
“…the basic biological phenomena that putatively underlie relations among nutritional experiences of early life and later diseases.”

92. 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

93. Metabolic Imprinting: Potential Mechanisms
Organ structure
Cell number & function
Clonal selection
Metabolic differentiation

94. 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.

95. 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

96. Cell Function:
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.

97. 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

98. 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

99. Fall et al, 1988

100. Gluckman et al. Biology of the Neonate, 2005

101. Topic 3 Public Health Approaches to Nutrition and Pregnancy Assessment
Policy Development
Assurance

102. Assessment
Planning for Pregnancy
Risk Behaviors

103. 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.

104. Effects of pregnancy planning status on birth outcomes and infant care (Kost et al. Family Planning Perspectives, 1998)

105. 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.”

106. Surveillance for Pregnancy
PRAMS results – Washington State

107. Alcohol

109. MMWR, December 24, 2004

110. Multivitamin Use

111. Multivitamin Use

112. Breastfeeding Duration

113. Breastfeeding Duration

114. Smoking

118. Unintended Pregnancy

120. Post-Partum Depression – PRAMS

121. Washington State PRAMS

122. WA State PRAMS

123. Key Indicators of Perinatal Health for Washington Residents: August 2005
The total number of live births has remained stable since 1998 at approximately 80,000 births per year.
Medicaid-funded deliveries represented 45.6% of births in 2003.
Birth rates and pregnancy rates decreased among teens years and years, especially from 1993 to 2003.
Since the mid-1990s, total infant mortality, race-specific infant mortality and Medicaid-specific infant mortality have decreased slightly.

124. Indicators, cont.
SIDS rates have decreased substantially since 1990, however changing reporting practices of coroners/medical examiners have played a role in this decline.
Smoking during pregnancy, as reported on the birth certificate, has declined since 1992.
In 2002, the percent of women initiating breastfeeding was high in Washington State at approximately 90%.

125. Areas of Concern in WA State
Total low birth weight has increased steadily since 1990, in part due to the increase in multiple deliveries.
In 2003, African American and Native American infant mortality rates continued to exceed infant mortality rates of other race and ethnic groups.
In 2003, the highest singleton low birth weight (LBW) rate was for African Americans.
Key Indicators of Perinatal Health for Washington Residents: August 2005

126. Concerns, cont.
The singleton VLBW rate among African Americans remained over twice the rate of Whites between 1990 and 2003.
In 2003, women receiving Medicaid had lower rates of first trimester prenatal care and higher rates of late and no prenatal care than women who did not receive Medicaid.
In 2003, smoking rates during pregnancy were significantly higher for women receiving Medicaid than for women who did not receive Medicaid.
In 2002, the unintended pregnancy rate was approximately 54%.

127. Healthy People 2010 Goals Related to Maternal and Infant & Nutrition

128. Reduce low birth weight (LBW) and very low birth weight (VLBW).

129. Reduce preterm births

130. 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.

131. Increase the proportion of pregnancies begun with an optimum folic acid level.

132. Increase abstinence from alcohol, cigarettes, and illicit drugs among pregnant women

133. Increase the proportion of mothers who breastfeed their babies

134. Increase smoking cessation during pregnancy
Target: 30 percent.
Baseline: 12 percent smoking cessation during the first trimester of pregnancy in (age adjusted to the year 2000 standard population).

135. 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 (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).

136. Reduce iron deficiency among young children and females of childbearing age.

137. 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 < g/dL) in 1996

138. Anemia Rates - 1996 African American, non-Hispanic 44%
American Indian/Alaska Native 31%
Asian/Pacific Islander 26%
Hispanic %
White, non-Hispanic 24%