27.01.2015

Pregnancy health risks by age

The Nebraska state government, realizing the tremendous mistake it had made, held a special session of the legislature to rewrite the law in order to add an age limitation. Last year, General Mills launched a new product aimed at health-conscious customers: Cheerios Protein, a version of its popular cereal made with whole-grain oats and lentils. Women with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes (T2DM); however, little is known about the association between other common pregnancy complications (eg, preterm birth, macrosomia) and T2DM risk. Women who experienced a very preterm birth or had an infant that weighed 10 pounds or more may benefit from lifestyle intervention to reduce T2DM risk.
A growing body of research suggests that pregnancy and the period surrounding it may provide unique information about a woman’s future risk of chronic disease (1,2). Despite the well-established association between GDM and future risk of T2DM (5,8), less is known about even more common pregnancy complications and future risk of T2DM.
The objective of our study was to examine the association between gestational age, birth weight, and T2DM in mothers. Study participants were from the Nurses’ Health Study II (NHSII) population, a cohort study of 116,678 female nurses who were aged 25 to 42 years at the start of the study in 1989. Our study population is based on a subset of the NHSII population who had detailed data on pregnancy history and T2DM. Study participants indicated the length of each of their 5 most recent pregnancies lasting at least 12 weeks in the following categories: 12 to less than 20 weeks, 20 to less than 24 weeks, 24 to less than 28 weeks, 28 to less than 32 weeks, 32 to less than 37 weeks, 37 to 42 weeks, and 43 or more weeks.
On the 1989 baseline questionnaire, study participants reported their current weight and height and their weight at age 18 (19). We used Cox proportional hazards models to examine the association between preterm and postterm birth, as well as low birth weight and macrosomia with T2DM risk, modeling gestational age and birth weight separately. Women were followed from their first birth through 2005 or up to 35 years after their first pregnancy; we were able to follow more than 95% of the cohort for up to 34 years after their first birth. In age-adjusted analysis, we observed a graded association of very and moderate preterm birth with risk of T2DM, as well as elevated risks among women delivering their first child postterm (Table 2). We explored the association between gestational age and T2DM in 5-year intervals following first pregnancy (Figure 2).
When evaluating absolute risk of T2DM for women who delivered an infant that weighed 10 pounds or more, we found an excess of 115 T2DM cases per 10,000 women in this group compared with women who delivered a normal weight infant in the 21 to 25 years following the first pregnancy.
Because the prevalence of screening for GDM and HDOP during pregnancy has changed over the period of the births in this cohort (1964–2001), we repeated the analysis among first births occurring after the baseline 1989 questionnaire, because after that time period, screening was more widely practiced as standard care and gestational age-dating of pregnancies had probably improved with the advent of ultrasound. In this study, the approximately 9% of women whose first infant was delivered preterm had excess risk of developing T2DM, even after accounting for potential medical and lifestyle confounders. In a previous study by Lykke et al based on vital statistics registry data from Denmark (23), preterm birth (<37 weeks) was associated with a 2-fold increased risk of T2DM in mothers after adjusting for maternal age, year of delivery, and pregnancy complications. The increased risk of T2DM among women who experience a preterm birth may be due to chronic low-level inflammation (25,26). Strengths of this study include use of a large cohort of nurses with detailed information on both pregnancy history and diabetes and information on pre-pregnancy and reproductive risk factors for diabetes.
Women who experience a preterm birth or have an infant with nonnormal birth weight are not followed up for lifestyle intervention or disease prevention after re-entry into the standard health care system for nonpregnant women.
But women without college degrees still make up more than half of those having babies after age 35, and the risks their children face have more to do with high blood pressure, obesity, diabetes, and other health conditions than with genetic or epigenetic mutations.
It is a religious group with carefully considered beliefs, among them that it is a key agent of the coming apocalypse.
We examined the associations between first-pregnancy preterm, postterm birth, low birth weight, and macrosomia with subsequent risk of T2DM. If replicated, these findings could lead to a reduced risk of T2DM through improved primary care for women experiencing a preterm birth or an infant of nonnormal birth weight. For example, gestational diabetes (GDM) is a well-established risk factor for type 2 diabetes (T2DM) in women (3,4). For example, preterm birth and low birth weight complicate more than 10% of US pregnancies (9,10). We evaluated these associations in a large cohort study, adjusting for potential confounders, including maternal and paternal history of diabetes, pre-pregnancy body mass index (BMI), and smoking during pregnancy.
NHSII follows participants biennially by questionnaire to obtain both health-related behavior information and data on the occurrence of diseases, including diabetes. Characteristics of the study population, 2001 Nurses’ Health Study II supplemental questionnaire. A recent validation of pre-eclampsia compared with medical record review showed self-reported preeclampsia is a moderately good indicator of hypertensive disorders of pregnancy (HDOP) (positive predictive value, 73%) (17).


First, we evaluated the association between gestational age, infant birth weight, and T2DM risk in first pregnancies for the entire 35-year follow-up period. We examined pregnancy complications and risk factors for all births and for term births in the study population (Table 1). In the first decade after very preterm birth, there was no increased risk of T2DM compared with term birth. We found that during the 6 to 10 years following the first pregnancy, only 12 excess T2DM cases per 10,000 women who experienced a moderate preterm birth occurred compared with women who delivered at term. After 30 years, the elevated risk associated with having delivered a large infant had disappeared.
The hazard ratios estimated by the fully adjusted models (including GDM and HDOP diagnoses) were stronger for birth weight and T2DM, which mitigated the concern that macrosomia in the earlier pregnancies might merely be a marker for undiagnosed GDM. The 2% of women who experienced a very preterm birth had a 34% increased risk of developing T2DM over the 35-year follow-up period.
UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). Mortality of mothers from cardiovascular and non-cardiovascular causes following pregnancy complications in first delivery. Prepregnancy lipids related to preterm birth risk: the coronary artery risk development in young adults study.
Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Preterm delivery and risk of subsequent cardiovascular morbidity and type-II diabetes in the mother.
Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. First, the overall consequences of the trend toward older parenting are on balance positive, both for women's equality and for children's health. Preterm births, low birth-weight and birth complications are major causes of developmental disabilities, and they occur most often among mothers with their own health problems.Most distressing, the effects of educational (and income) inequality on children's health have been increasing. For the vast majority of that group, the sequence Shulevitz describes is not relevant.In fact, if Shulevitz had considered economic inequality, she might not have been quite as worried about advancing parental age. Although up to 70% of women who develop GDM will eventually develop T2DM within the first 5 to 20 years following pregnancy (5), several studies have shown that lifestyle interventions immediately following pregnancy lead to a significant reduction in T2DM risk (6,7). We also adjusted for lifestyle and reproductive factors as well as pregnancy complications known to be predictors of T2DM. In addition, the 2001 supplemental questionnaire asked about smoking status during pregnancy (eg, ever, never). Second, we explored time since first birth in 5-year intervals up to 35 years after the first pregnancy to determine at what time points the differences between gestational age or birth-weight groups were significant.
However, there was an inconsistent change in risk in the second decade, which reached statistical significance. By 26 to 30 years after the first pregnancy, 298 excess T2DM cases per 10,000 women who delivered a very preterm birth occurred compared with those who delivered at term. Associations between macrosomia and subsequent risk of T2DM were only significant between 6 and 20 years after the first pregnancy. However, the association of very preterm delivery with T2DM was no longer detectable when limiting the analysis to pregnancies occurring after 1989. In an exploratory analysis, we found that the elevation in risk first became evident at 11 to 15 years after the first pregnancy. As such, preterm birth could signal a chronic state of inflammation and an increased risk of future development of T2DM.
However, validation studies demonstrated good self-report of related pregnancy factors (16,19).
If our findings are replicated, women who experience a preterm birth or have a nonnormal birth-weight infant may benefit from additional follow-up and lifestyle intervention to reduce their subsequent risk of T2DM.
The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. On that purple chart, a college graduate in her early 40s has the same risk as a non-graduate in her late 20s. Preterm birth and low birth weight share common underlying risk factors with T2DM, including elevated pre-pregnancy and pregnancy lipid concentrations (11,12) and inflammatory markers (13,14). Finally, we explored the time trends in risk over the decades following birth of a preterm infant or an infant of nonnormal birth weight to suggest potential windows for prevention and glucose tolerance screening after complicated pregnancies.


BMI was derived for ages at which weight was not reported (ie, between age 18 and age at the baseline questionnaire) from a formula using weight at age 18 and weights reported on biennial questionnaires, as well as somatograms at ages 20, 30, and 40 to assign BMI at each age starting at 18 years and through the end of the study period.
Participants were also asked at baseline to report their menstrual regularity at age 18 to 22 years, which was categorized as regular, irregular, or no menstrual periods. No significant associations were found after 21 years following first pregnancy among women with a very preterm birth. Postterm birth was associated with a slight, significant increase in risk of T2DM over the entire 35-year period. Another study by Catov et al found 76% increased odds of metabolic syndrome among women with a previous preterm birth 8 years following pregnancy (24).
Moderate preterm and term low birth weight did not significantly increase the risk of T2DM over the 35-year follow-up time.
These shared biological factors suggest that preterm birth and low term birth weight may be early markers of subclinical risk of future development of T2DM.
To restrict the analysis to cases likely to be T2DM, we included women who reported having diabetes mellitus on the 1989 questionnaire only if they were age 30 years or older at the time of diagnosis. We adjusted for potential confounders, those factors that preceded pregnancy complications of interest and were associated with diabetes mellitus. In contrast, women who had a moderate preterm birth had significant, roughly two-fold, increased risk of T2DM for the first 10 years after their first pregnancy, which thereafter returned to the baseline risk of women who had delivered at term. A history of having borne a first infant who was term low birth weight or macrosomic conferred an almost 2 to 3-fold increased risk of T2DM, which gradually waned over time.
We observed a very similar 2-fold increased risk of T2DM after a moderate preterm delivery (<37 weeks) in the first 10 years after pregnancy. This technique allowed us to explore periods in which certain pregnancy complications may have the most predictive value for future development of T2DM.
Second, we used categories of gestational age and birth weight instead of continuous measures, which may make it difficult to see subtle changes in disease risk.
In addition, giving birth to a macrosomic infant (10 pounds or more) could suggest an increased risk of future maternal T2DM in the absence of GDM or could result from undiagnosed GDM. Finally, we used the Breslow estimator to calculate the age-adjusted risk differences from the Cox proportional hazards models.
However, we were able to follow our cohort for an additional 20 years, which indicated that the excess risk associated with a history of moderate preterm birth was limited to the first 10 years after pregnancy.
In fact, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study found a continuous association between maternal hyperglycemia and increasing birth weight (15).
Future studies are needed to further explore and confirm these associations based on time since pregnancy.
Furthermore, these categorizations prevented us from examining small-for-gestational age or large-for-gestational-age infants; as such we had to restrict our analysis of birth weight to term births. Health-wise, assuming she births the rest of her (small) brood before about age 35, that's perfect.Consider two measures of child well-being according to their mothers' age at birth. If our findings are replicated in future studies, gestational age and offspring birth weight may be useful to identify high-risk women. The risk associated with very preterm birth, however, arose after the first decade following the first pregnancy and remained modestly elevated throughout the 35 years of follow-up. Thus, our finding of an early elevation in T2DM risk for women who delivered infants that were term low birth weight may not be generalizable to women who delivered preterm infants, who were small for gestational age.
Rich-Edwards, Brigham and Women’s Hospital, Harvard Medical School, and Harvard School of Public Health, Boston, Massachusetts. If such associations are found, women experiencing these complications could potentially benefit from early intervention to reduce future T2DM risk.
However, the weakening over time of relative risk associated with preterm delivery and infant birth weight may reflect the increasing prevalence of other T2DM risk factors with increasing age (study time), including high BMI and increased sedentary behaviors.
Therefore, our findings may suggest that these pregnancy complications may be especially useful predictors of early-onset T2DM. Finally, we had limited ability to evaluate this association among minorities, who have both a higher prevalence of these pregnancy complications and T2DM.




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