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Pregnancy and Pregnancy Outcomes White Paper (PDF - 224KB)

Created on May 11, 2011



35 Submitted Comments on Pregnancy and Pregnancy Outcomes

This white paper provides many compelling directions for research on pregnancy and pregnancy outcome including visionary use of new tools and methods. The themes of cross-national collaborations, challenges in the developing world, and the likely shift in disease burden make clear the need to include developing country settings. In all settings, but especially in the developing world, the challenges of pregnancy during adolescence are considerable. In settings wehre child marriage is still common ? and there are many ? half of the girls in a community may be married by age 15, and married to an older husband and with pressures to bear children early. The context in which that pregnancy is taking place brings significant physiological and social implications for the mother and child (not to mention challenges for the health care system). Given the recognition of social factors and international challenges, it would be beneficial to explicitly address the issues surrounding adolescence in terms of pregnancy and pregnancy outcome.

Submitted by wendy Baldwin on May 12, 2011 at 1:06 PM

We read with great interest the white papers on pregnancy and reproduction and agree with the importance of many of the ideas presented. We are deeply concerned, though, with the almost complete exclusion of the social science perspective and, particularly, economic analysis. The primary oversight is the implicit view that pregnancy and reproduction are largely outcomes that result from biological processes. The role that behavior plays is almost completely ignored. We need to understand both the biology and the behavior if we interested in research focused on promoting that ?every child is wanted and reaches their full potential.? If we only know how the body works, but not how or why individuals make decisions, we will fall short of that goal. For decades, economists have usefully studied fertility. For illustrative purposes, we describe some of our own work on teen and non-marital childbearing. One advocated approach to reducing these pregnancies is to increase access to contraception. Improved access will only be effective if women are committed to avoiding pregnancy and that it serves those who were not already using contraception. This is about behavior, not biology. We investigated how expanded family planning services under Medicaid affected fertility, finding that the policy reduced births to newly-eligible women by almost 9 percent (Kearney and Levine, Review of Economics and Statistics, 2009). We have also explored how background disadvantage affects rates of early childbearing (Kearney and Levine, in An Economic Perspective on the Problems of Disadvantaged Youth, 2009.) We confirm a strong empirical correlation at the individual level, but find that even large changes in the rates of disadvantage among a cohort would not be very effective at reducing aggregate rates of teen childbearing. Levine has used econometric tools to examine the impact of abortion policies on pregnancy and childbearing (Levine, Sex and Consequences, 2004). Kearney has empirically examined the impact of the welfare reform ?family cap? (Kearney, Journal of Human Resources, 2004). The purpose of this comment is to advocate for the value of social science research, and economic analysis in particular, in addressing critical issues in reproductive health. It would be a complete travesty if the insights and analytic methods of social scientists, including economists, are excluded from the NICHD vision.

Submitted by Phil Levine on May 18, 2011 at 2:14 PM

An additional important research area to include in NICHD?s mission related to pregnancy and pregnancy outcomes is the interaction of pregnancy (the pregnancy woman, placenta, fetus, and newborn) with infectious organisms. For example, infections, particularly malaria and syphilis, are a leading cause of stillbirths and accounts for an estimated half of all stillbirths, especially in developing countries. Untreated HIV infection is associated with prematurity and low birth weight. Up to half of the 3.5 million low birth weight babies born in sub-Saharan Africa each year may be attributable to placental malaria; spontaneous abortion and preterm delivery is also associated with placental malaria, and these fatal complications result globally into an estimated 75,000?200,000 deaths of infants each year. The role of infection-related cytokine changes in the placenta in the pathogenesis of adverse outcomes needs study. Infections are one of the three major causes of neonatal death. Mechanisms of transmission (and protection from transmission) of infectious agents need to be better elucidated in order to develop preventive interventions. NICHD plays an critical role in ensuring that research on infections also includes pregnant women, studies of effect of infections on pregnancy outcome, and mother to child transmission of infectious agents.

Submitted by Lynne Mofenson on May 18, 2011 at 6:04 PM

This document seems focused entirely on pregnancy and pregnancy outcomes in the US. There is no mention of the enormous problems of maternal morbidity and mortality related to pregnancy and neonatal mortality in low resource settings. Continued research on interventions to improve the health of women and infants in low resource settings should be part of the NICHD mission, and new technologies discussed in this white paper have potential to further this mission.

Submitted by Heather Watts on May 19, 2011 at 3:20 PM

While research on prenatal testing and screening has been thought to be the exclusive domain of biomedical researchers, insights from economics and decision sciences - much of it funded by NICHD - have improved our understanding of these tests, how pregnant women make decisions about them and ways to help them improve their decisionmaking. Economists and decision-theory scientists have made important contributions to our understanding of how to conceptualize these decisions processes and help expectant parents make more informed decisions. Research by Fajnzylber, Hotz and Sanders (2010) [FHS] funded by NICHD (R01HD34293) contributes to this by recognizing that pregnant women may take account of the fact that outcomes for one pregnancy affects future fertility choices. In their model, an amniocentesis carries with it the risk of experiencing a miscarriage but women, by not undergoing an amniocentesis, can limit this risk. At the same time, by not having an amniocentesis, pregnant women increase the risk of bearing a child with Down syndrome. In FHS?s model, pregnant women will take account of the fact that if they experience an amnio-induced miscarriage, they have the option of still having a chromosomally-normal birth at later ages as well as the fact that this option decreases as these women approach menopause. The latter two points distinguish FHS from other genetically-determined or static decision-theoretic models of amniocentesis choice. The former models will always have a rising propensity to choose to undergo an amniocentesis to the extent that pregnant women prefer to avoid a child born with a genetic disorder. But the dynamic model of FHS, the propensity of women to choose an amniocentesis may or may not rise with maternal age. Since they balance the benefits associated with having an amniocentesis (avoiding having a child with a genetic disorder) with the costs associated with them (running the risk of a procedure-induced miscarriage of a healthy fetus). FHS show that their model can explain the following two ?stylized facts? about how amniocenteses vary with pregnant women?s age and birth parity. First, while amniocenteses begin to rise at age 35, they decline after age 40. Second, this decline in amniocenteses at older ages is greater for women who had not yet had a birth than for those with 3+ children. Based on calibrated simulations of their model, FHS show that they can account for both of these stylized facts.

Submitted by V. Joseph Hotz on May 19, 2011 at 5:05 PM

It is important to have the pregnancy and pregnancy outcomes program interdigitate with the peri-conception program. What happens to women and men's health just in their childbeaing years impacts on pregnancy outcomes. What if inexplained preterm birth is programmed into an egg or sperm prior to conception. The divisions at NICHD greatly hamper our abiltiy to study these issues. The NIH infrastructure does impact on the science that is funded and conducted. To explore this area would be to truly revolutionize the field.

Submitted by Anonymous Guest on May 20, 2011 at 3:48 PM

The vision workshop paper on Pregnancy and Pregnancy Outcomes is right on target for where the emphasis should be placed on research to improve maternal and neonatal outcomes. The following opportunities will likely be of highest impact:
1) The emphasis on observational studies as a research priority to define biomarkers and molecular pathways for rigorously phenotyped adverse pregnancy outcomes (APO) such as spontaneous preterm birth, preeclampsia, fetal growth restriction as well as data about environmental and behavioral data. This is necessary before clinical trials can be adequately designed. Being able to predict which women are at the highest risk for APO, (prior to the development of overt clinical symptoms) is important prior to designing interventional RCTs . In addition, as pointed in the paper, lumping all preterm birth together when the causes of early preterm birth (< 32 weeks) and late preterm birth are different has hindered research thus far.
2) Development of well characterized reproductive cohorts with high quality biological specimens and clinical data that allows for assessing maternal, placental, and fetal compartments is crucial. In order to be able to do this, there is a need to support the collection of data and biological specimens across the 24/7 clinical schedule as pointed out in the paper
3) Emphasis on placental biology and development is crucial to understand APO (ability for non-invasive assessment (ultrasound/MRI), primate models and CVS specimens).
4) Adopting standardized, uniform definitions for pregnancy outcomes would facilitate research as well as clinical care. For example, the reasons for CD-"failure to progress", "labor arrest", etc. differ across hospitals making research difficult.
Possibly holding a conference sponsored by NICHD, ACOG, SMFM, etc. would facilitate this.
5) Longitudinal study of cardio- metabolic maternal outcomes post-pregnancy is high priority given the burden of heart disease in women and because pregnancy serves as the first "screening" test for most women
6) Support trainees especially those S/P NIH funded training program to perform transdisciplinary research - need to support them post training in obtaining first independent grant funding- ?differential payline, new grant mechanism
Will there be an opportunity at the end of the visioning process to examine the research studies that are currently funded by NICHD to determine if these research gaps can be addressed?

Submitted by Uma Reddy on May 23, 2011 at 11:20 AM

I urge the NICHD to integrate lactation into pregnancy research as a fundamental part of normal reproductive physiology. From a public health standpoint, curtailed lactation is major predictor of morbidity for mother and child. Infants who are not breastfed face increased risks of otitis media, gastroenteritis, lower respiratory tract infections, obesity, diabetes, childhood leukemia, sudden infant death syndrome, and necrotizing enterocolitis. Among mothers, not breastfeeding is associated with increased risks of type 2 diabetes, breast and ovarian cancer, and myocardial infarction. Thus not being breastfed is thus a major developmental exposure that affects long-term health and disease. The prevalence of suboptimal breastfeeding is substantial: one quarter of US infants are never breastfed, and 87% of mother-infant dyads are unable to achieve the consensus-recommended 6 months of exclusive breastfeeding.

A considerable body of research has documented sociodemographic determinants of breastfeeding rates, but there are limited data regarding the basic physiology of lactation or management of common clinical problems that lead to early weaning. More than half of women in a recent CDC study reported weaning earlier than they wanted to, underscoring the need for evidence-based treatments to address common problems. Longitudinal studies are needed define the physiology of normal lactation and unravel the pathophysiology of common complications such as insufficient milk production and chronic breastfeeding associated-pain. Furthermore, breastfeeding outcomes should be routinely assessed in perinatal clinical trials. For example, consider NICHD-funded studies of progesterone to prevent preterm birth. Provision of human milk to preterm infants is associated with a 5% absolute reduction in risk of necrotizing enterocolitis, and is therefore of paramount importance in this population. Progesterone withdrawal is considered an essential determinant of lactogenesis. However, timing of lactogenesis and subsequent milk production were not quantified in studies of progesterone to prevent preterm birth.

In conclusion, the prevalence of suboptimal breastfeeding is high, and the pathophysiology is poorly understood. Research to define the underlying biological mechanisms has the potential to impact key health outcomes for mother and child. I urge the NICHD to include lactation in its Visioning priorities for the coming decade.

Submitted by Alison Stuebe on May 23, 2011 at 11:34 AM

This white paper does a remarkable job of delineating the complexity of the research needed to improve pregnancy outcome. The focus on the importance of tools to assess placental function and fetal well-being is particularly valuable.
In the discussion of the "gestome", animal models were highlighted to analyze the biological networks of pregnancy. It also would be good to emphasize the importance of studies in humans to understand the basic biology of these networks and normal fetal development. In the discussion of pregnancy as part of the life-course, the "life-changing" aspects of pregnancy were not emphasized. Many women change their behaviors with the knowledge they are carrying a child. What are the biological and social determinants of these maternal protective/resilient behaviors? How can these be used to improve pregnancy outcomes?

Submitted by Marian Willinger on May 23, 2011 at 1:24 PM

I laud the systems biology approach (referred to as the "gestome") to pregnancy, integrating both human and animal studies. Only in using this holistic approach can a true understanding of pregnancy be achieved. In regard to animal models, the emphasis of mouse models is obvious because of their low cost and genetic manipulability; however, one must not lose sight of the obvious relevance of using non-human primate models were feasible.

Submitted by John V. Ilekis Guest on May 24, 2011 at 9:26 AM

Although this is one of the better papers, it does present the researcher/clinician point of view. I agree with the recommendation that we need to better understand the decision making processes regarding labor and delivery. However, while algorithms may be developed to "account for competing risks," in the end this information should be used by the pregnant woman and her clinician to determine what decision she should make, and not make the determination for her. Similarly, the report on breakout session 2 did not adequately acknowledge the pregnant woman's expectations or role in balancing maternal and fetal risks and benefits.

Submitted by Lisa Kaeser on May 24, 2011 at 1:11 PM

The White Paper produced by the National Institute of Child Health and Human Development sponsored Scientific Vision Workshop on Pregnancy and Pregnancy Outcomes emphasized the importance of research from biology. In contrast, relatively little consideration was given to the role of social scientists, and in particular economists, in advancing knowledge related to pregnancy and pregnancy outcomes. Economists have made many contributions to knowledge about pregnancy and pregnancy outcomes.

Consider the issue of preventing Cesarean deliveries, which was one of the seven areas covered in the White Paper. The White Paper focused on clinical issues related to this problem. This focus ignores the significant amount of research by economists that has demonstrated that Cesarean deliveries are greatly influenced by financial considerations. Studies by economists have shown that the prevalence of Cesarean deliveries depends on the price of Cesarean deliveries vis-?-vis vaginal delivery. Similarly, economists have shown that the prevalence of Cesarean deliveries depends on financial pressure on physicians to deliver by Cesarean methods stemming from the medical malpractice liability system. Future research efforts in this area should incorporate the economic perspective and research by economists.

Another area the White Paper highlights is the effect of the external and intrauterine environment on the developing fetus. Here too, the White Paper emphasized biologic and clinical research. Economists, however, have made important contributions to this problem. Most importantly, economists have identified specific environments such as inadequate nutrition caused by famine and other man made and natural disasters, adverse economic conditions, both at personal and macro level, and physical environmental insults such as air pollutants that have adversely affected fetus development. It would be prudent for future research efforts to include the research perspective and research tools of economists to help improve pregnancy outcomes.

Submitted by Robert Kaestner on May 27, 2011 at 1:07 PM

The Endocrine Society appreciates the opportunity to provide feedback on the white papers developed from the Vision Workshops held by the NICHD. The Society lauds the transparent and reciprocal approach taken by NICHD in the generation of its scientific vision that will inform the Institute's direction for the next decade. A significant portion of the Society's basic researchers apply for funding through NICHD, and the NICHD Scientific Vision is of particular interest to our membership. Given the tremendous overlap between Society members' research interests and those of the NICHD, The Endocrine Society considers the Institute's scientific visioning process to be an important milestone for the continued advancement of endocrine science.

It is imperative that NICHD continue to fund investigator initiated, independent research into basic physiological processes surrounding pregnancy and pregnancy outcomes. Continued support of basic research will provide the basis for advances in understanding pregnancy complications, pregnancy related diseases, and pregnancy outcomes.

We are pleased to see a discussion of the long-term aspects of metabolic changes in pregnancy included in the white paper, as this is highly relevant to the Society and its members. However, one neglected aspect of pregnancy outcomes is breastfeeding, an important component of postpartum maternal and child health. The scientific vision would benefit from the inclusion of research aims concerning breastfeeding, such as potentially decreased rates of obesity, diabetes, and acute chronic illness in children and the beneficial metabolic and breast health effects in the mother. Furthermore, the inclusion of efforts to understand and improve the prediction of postpartum depression would be valued additions.

Again, the Society appreciates the opportunity to comment on the white papers made available by NICHD and recognizes the efforts of the workshop participants in compiling the documents that will shape the future of the Institute. Endocrine research is a vital component of expanding our understanding of pregnancy and pregnancy outcomes, and Society members are enthusiastic about potential opportunities that may be presented by the Institute as a result of its rigorous planning. We believe that the inclusion of the topics described above would be valuable additions to the Pregnancy and Pregnancy Outcomes white paper and to the NICHD Strategic Plan.

Submitted by Kelly Mayo on June 1, 2011 at 11:31 AM

While this white paper raised some important and interesting ideas for future research directions on pregnancy and pregnancy outcomes, it was also narrowly focused on biological/medical approaches and included very little social scientific or population-based content. As a result, some very important research issues and opportunities in the area were completely untouched, which if left this way, would be extremely shortsighted for future NICHD-sponsored research in this area of study. I will provide just two key examples here, but there could be many others.

1) Racial/Ethnic and Socioeconomic Disparities in Pregnancy Wantedness, Single Parenting, Prenatal Care Utilization, Cesarean Section Delivery, Birth Outcomes, Infant Mortality, and more. Just one sentence on page 1 of the report is devoted to the issue of disparities: "Moreover, despite years of directed research and public concern, disparities in maternal health and birth outcomes have only grown over the past decade (Alexander et al. 2008; IOM 2006; Wise 2004)." This raises a critical question of research priority: if racial/ethnic and socioeconomic disparities in maternal health and pregnancy outcomes are "only widening", why is this the case? Shouldn't this issue climb to the forefront of research priorities on this topic at NICHD, given that our general progress to this point has fallen woefully short of national goals? Arguably, this topic could have been the leading research issue in the area for the next decade, but was simply not at all considered throughout the remainder of the white paper.

2) Increases in Non-marital Pregnancy and Childbearing and Socioeconomic/Health/Developmental Implications. NCHS continues to document an increasing proportion of U.S. children born to non-marital parents, which is now around 40 percent. Since 1998 or so, the NICHD-sponsored Family Families and Child Wellbeing Study led by Sara McLanahan at Princeton University has given the research community and policymakers enormous insights on these issues, but at the same time, that study was just one cohort of individuals with a relatively modest sample size. Moreover, families and family structure have continued to change very rapidly in the United States, with unknown implications for new parents, their children, and their grandchildren.

Submitted by Robert Hummer on June 9, 2011 at 11:33 AM

The white paper recognizes the importance of a model that integrates influences on pregnancy from genes to organisms to environments (social and physical/chemical). This comment raises issues critical to achieving this vision, and notes the importance of a population perspective in the development of strategies to improve pregnancy health at the population level.
1. Conceptualization and measurement of environment in the context of multi-level studies remains challenging. We need to better define what is meant by environment at different levels of exposure (from the cell to the society) and model the processes through which various exposures occur. For example, because organisms have behavioral control over some kinds of exposures, behavior can be pivotal in the structure of multi-level models. Behavior responds to social and cultural exposures in the environment and affects what exposures an individual experiences. The behavioral and social sciences have developed a sophisticated body of knowledge about these processes; the challenge is to bridge this knowledge with knowledge of the maternal and in utero "exposome" and its effects on pregnancy. This will require creative and patient interdisciplinary work focused on specific exposures.
2. It is important to recognize that the biology of individual pregnancies can be influenced by how the pregnancies came about. About one half of pregnancies occur unintentionally; these pregnancies have poorer outcomes than those that are planned even after controlling socioeconomic differences, but the mechanisms accounting for this need further study.
3. Studies of the effects of pre-pregnancy health on pregnancy that limit participation to women planning pregnancy do so at a steep cost: that of losing very significant variation in the circumstances that produce poor pregnancy outcomes. The study of pre-pregnancy health needs to develop innovative designs for recruitment that do not depend upon pregnancy planning as a condition for recruitment.
4. A population perspective on pregnancy and pregnancy outcomes is needed to complement the focus on individual outcomes. The population level focus asks, how can we devise strategies at the population or community level that will improve outcomes and reduce disparities? Both perspectives benefit from the interdisciplinary effort envisioned by the white paper, and both are essential to NICHD's contribution to improving pregnancy health.

Submitted by Christine Bachrach on June 9, 2011 at 3:13 PM

On behalf of the Preeclampsia Foundation, we congratulate you on a very thoughtful overview of the needs for future research. We have many areas of agreement such as the need to understand "normal" biology during pregnancy if we are to properly understand the pathophysiology that leads to adverse pregnancy outcomes such as preeclampsia (PE) and HELLP syndrome. PE is a great "poster child" for viewing pregnancy as a life course event, one with a critical role in relation to future health. PE, a disease that impacts up to 1 in 12 pregnancies, is a multi-system disorder, and could stand in as the example to almost every theme and strategy described. The burden of disease in this area impacts the lives of two patients. We suggest the following areas of research needs:
We still do not understand what initiates PE nor completely understand its pathophysiology. Basic research that includes recently developed and pertinent small animal models, placental preparations, primates and materials obtained from women with preeclampsia, as well as studies that address the holistic genesis of disease, including the impact of modifiable behaviors, should rate a high priority. Areas of follow-up interest include angiogenesis, immunology, and inflammation, obesity and molecular genetics. Interdisciplinary collaborations are encouraged.
Translation studies are critical. Combine resources within and across the Institutes to develop a clinical trials network dedicated to PE. Clinical trials and observational studies with ancillary studies stressing mechanism should focus on a growing reservoir of circulating protein markers and the long neglected area of antihypertensives in general. For instance, it has been three or more years since the identification of a good animal model where the reversal of key lesions by adding VEGF 121 were published, yet we have not extended these to human trials. We support the current development of consortiums to extend the leverage of the many existing biorepositories and registries and create an effective framework for new collections. Efforts to safely remedy the hesitancy to perform therapy trials in pregnant women must be addressed.
Attempts should be made to optimize diagnosis and therapy through health services, health literacy, and knowledge transfer research, as well as public education campaigns to improve how the care provider and patient can most effectively recognize and manage PE. This also impacts PE's huge global health dispariti

Submitted by Eleni Tsigas on June 9, 2011 at 6:10 PM

On behalf of the Population Association of America, I am pleased to comment on overlooked opportunities in the Pregnancy and Pregnancy Outcomes white paper.

Racial/Ethnic and Socioeconomic Disparities--Recent NICHD-supported work shows that U.S. infant mortality rate disparities by race/ethnicity have either widened or narrowed, depending upon whether they are examined from a relative change or absolute change perspective. More research is needed to understand these trends and answer important questions such as: Which racial/ethnic and socioeconomic groups continue to be at highest risk and why? How do different forms of discrimination affect the health of women, pregnancy, and pregnancy outcomes? What challenges, needs, and unique contexts do recent immigrants and undocumented immigrants face with regard to pregnancy and pregnancy outcomes? What data is needed to analyze high levels of adverse maternal health and pregnancy outcomes among some racial/ethnic minority and economically disadvantaged groups? What can be done to reduce adverse outcomes in disadvantaged populations?

Implications of Non-marital Pregnancy and Childbearing --The increasing proportion of U.S. children born to non-marital parents and constantly changing U.S. family structures has unknown implications. Research is needed to address specific questions posed by these changing dynamics including: How do children born to unmarried parents in the U.S. differ from children born to unmarried parents in other countries? What can we learn through such cross-national comparisons? What particular social, economic, health, and developmental risks do U.S. children of unmarried parents face compared to U.S. children of married parents? These issues can be added to the "Pregnancy as a Lifecourse Event" section.
Issues Surrounding Adolescence and Pregnancy and Pregnancy Outcomes--In all settings, but especially in the developing world, the challenges of pregnancy during adolescence are considerable. In settings where child marriage is still common, half of the girls in a community may be married by age 15, with pressures to bear children early. The context in which that pregnancy is occurring brings significant physiological and social implications for the mother and child and the health care system. Thus, NICHD should support research to explicitly address issues surrounding adolescence in terms of pregnancy and pregnancy outcomes.

Submitted by David Lam on June 10, 2011 at 8:56 AM

A few thoughts. There could be more discussion on the complications of preterm and the role of late preterm birth in poor outcomes. There should be strong motivation to make the datasets and biosamples collected by the NICHD networks such as MFM and Neonatal Network widely available to the community at large for datamining and new studies to convert these wonderful efforts more quickly into results than is currently happening. In addition they need to coordinate their efforts to allow combined analysis of common phenotypes (and to indeed collect common phenotypic data) to provide power to GWAS and genome wide sequencing efforts that are underway but are poorly coordinated and under powered as individual studies. These shared efforts should include eventually not only large clinical trials or other contract collection methods but eventually individual research projects to allow bioinformatic merging of data and common access to samples for the large scale studies needed to find genetic and environmental risks. Lastly similar partnering with other institutes collecting such data should also be on the agenda.

Submitted by Jeff Murray on June 10, 2011 at 10:06 AM

Include the findings from the NICHD meeting on Pregnancy in Women with Physical Disabilities, January 25-26, 2010 http://www.nichd.nih.gov/about/meetings/2010/pages/012610.aspx within this vision statement, including Available Evidence of Pregnancy Outcomes in Women with Physical Disabilities, Available Evidence of Pregnancy-Associated Risk to Mother and Baby in Women with Physical Disabilities, Epidemiology and Identifying and Overcoming Barriers

Submitted by Alexandra Enders on June 10, 2011 at 12:54 PM

I write on behalf of Childbirth Connection, a national non-profit organization that has worked to improve maternity care quality for 93 years. We support the priorities and general direction in the Pregnancy and Pregnancy Outcomes White Paper and appreciate the opportunity to offer suggestions to strengthen this framework.

Understanding the Biology of Pregnancy
We strongly endorse this theme. Currently, even healthy low-risk women are likely to have childbirth externally managed in multiple ways (e.g., induction, augmentation, amniotomy, directed pushing, c-section). Today's caregivers often have little awareness of the hormonal orchestration of parturition, breastfeeding, and attachment, and ways that common maternity practices interfere with this. Caregivers are losing core knowledge and skills for supporting childbirth (e.g., vaginal breech, vaginal twins, skillful judicious assisted delivery; breadth of ways to foster labor progress and comfort, confidence in VBAC). We hope NICHD will help ensure that tomorrow's maternity caregivers have knowledge and skills to protect, promote, and support physiologic childbirth; to help bring deviations back into the normal range; and to effectively address problems with minimal adverse effects.

We encourage NICHD to include in the "exposome" exposure of women and fetuses/newborns to common obstetrical practices. Validation studies have found that birth certificates and discharge data undercount some of these interventions. The national Listening to Mothers II survey found the following rates of intervention in women who gave birth in U.S. hospitals in 2005: one or more methods of labor induction (41%), epidural/spinal analgesia (76%), narcotics (22%), augmentation (47%), amniotomy (65%), episiotomy (25% of vaginal births), directed pushing (75% of vaginal births), supine birth position (57%), c-section (32%), mother-baby separation after birth for routine care (39%). Also, 99% had one or more ultrasounds, and 59% had 3 or more. Mothers who planned to exclusively breastfeed experienced high rates of disruptive hospital practices (e.g., 66% received free formula samples or offers, 38% of their babies were given water or formula supplements, and 44% were given pacifiers). The survey report is at www.childbirthconnection.org/listeningtomothers/. The "Precautionary Principle" of environmental health must also guide the care of childbearing women and newborns: we must identify and provide effective care with least

Submitted by Carol Sakala on June 10, 2011 at 1:24 PM

Second of six submissions from Childbirth Connection:

Applying Biology in Clinical Settings
For this theme, we encourage NICHD to give equal weight to potential benefits and potential harms. There is an understandable optimism bias throughout medicine. Naturally, caregivers want to help; benefit is commonly expected, while harms are frequently inadequately considered, measured, reported, and recognized. The Listening to Mothers II survey found that women overwhelmingly wanted to know all or most possible harms before agreeing to consequential interventions, but their knowledge about such harms was poor, even when they had experienced the intervention.

Childbirth Connection strongly supports greater attention to women's pregnancy outcomes. At present, no maternal morbidity is routinely measured in a standardized way after women are discharged from hospitals. Further, RCTs typically do not follow women up after hospital discharge. This is shortsighted; for example, a Danish registry study found that 77% of the incidence of postpartum infection occurred after hospital discharge, and cesarean mothers experienced five times as many infections as vaginal birth mothers (Leth RA et al. Acta Obstet Gynecol Scand 2009;88(9)). Without systematic measurement and reporting, women's postpartum outcomes are poorly recognized in the United States, with inadequate attention to prevention, treatment, and coordination with primary care. Some studies, including Listening to Mothers II and a follow-up survey with the same women six months later, have documented an alarming range, rate, and duration of new-onset physical and emotional maternal morbidities in the postpartum period. Please see Table 1 in the New Mothers Speak Out report available at www.childbirthconnection.org/listeningtomothers/ for the extent of specific problems that new mothers experienced in the first two months after birth and the extent to which the problems persisted to six months or more. The first Listening to Mothers survey found that, with the exception of infections, the mothers rarely brought problematic new-onset postpartum conditions to the attention of a health professional (likely impacted by the fact that maternity care comes to an end in the early postpartum weeks).

Submitted by Carol Sakala on June 10, 2011 at 1:26 PM

Third of six submissions from Childbirth Connection:


Viewing Pregnancy as a Life Course Event
As with the Biology of Pregnancy theme, Childbirth Connection strongly encourages NICHD to include medical exposures in the "exposome" framework. For example, there is emerging evidence that cesarean section increases a newborn's risk for impaired immune function (gut colonization with undesirable bacteria), type 1 diabetes, asthma, eczema, celiac disease, and obesity. Studies increasingly associate late term and even early term deliveries with a concerning array of adverse child developmental effects. For women, cesareans are associated with increased severe downstream reproductive problems, adhesions, and chronic pain. Cesareans are associated with reduced breastfeeding, which in turn fails to confer numerous long-term benefits to women and newborns. It is also important to understand the pelvic floor implications of such common practices as directed valsalva pushing, supine delivery positions, fundal pressure, and episiotomy and to compare these practices with less invasive and more physiologic approaches to care. Occurring at the beginning of life, in the context of common and potentially overused care and underuse of other possible beneficial approaches, and in the context of growing recognition of the developmental origins of health and disease, this line of investigation is imperative and urgent.

Developing Tools Needed to Advance Research
Childbirth Connection strongly supports the multi-disciplinary approach that is espoused here. However, we encourage clear inclusion of the perspectives of family physicians, midwives, nurses, consumers and their advocates, and purchasers (e.g., business coalitions and Medicaid leaders). In our experience, bringing these and more perspectives together is fruitful, and increases the quality of processes and products and uptake of the results. Tomorrow's maternity care system needs all caregivers and stakeholders to contribute and work together as a high-functioning team.

Submitted by Carol Sakala on June 10, 2011 at 1:27 PM

Fourth of six submissions from Childbirth Connection:

New Methodologies
Childbirth Connection encourages NICHD to address historic concerns associated with RCTs and other prospective studies of maternity care. First, while convenient and relatively inexpensive, it is very premature to end data collection at intrapartum hospital discharge. It is imperative to follow women and newborns into the postpartum period and beyond, as shown by numerous studies of postpartum well being, including Table 1 results of a national survey of new-onset maternal morbidity in the first two months postpartum and persisting to six months or more in the New Mothers Speak Out report, available at www.childbirthconnection.org/listeningtomothers/. Second, when calculating sample size, it is important to factor in study group crossover (impacted by often well-established expectations and preferences of health professionals and women). Trialists who looked at implications of this problem for an epidural study found that whereas they planned to enroll 1,200-2,200 participants, they would have needed to enroll 12,000 participants to measure a difference in light of the crossover that actually occurred (Dickinson JE et al. Aust NZ J Obstet Gynaecol 2002;42(1)). Also, in the planning, implementation, and reporting of research, we strongly encourage multi-disciplinary, multi-stakeholder collaboration and consultation, including the full complement of maternity caregivers and consumers and their advocates. This inclusive principle, which was recently affirmed by Institute of Medicine reports on standards for systematic reviews and clinical practice guidelines, applies as well to primary research.

Balancing Maternal and Fetal Risks and Timing of Delivery
In addition to focus on late preterm births, Childbirth Connection strongly encourages NICHD to focus on implications of early term births, which are increasingly recognized to have troubling and measurable effects on NICU admissions, respiratory problems, mortality, and developmental trajectories. We appreciate the attention in this section of the White Paper to unintended consequences of obstetric interventions.

Submitted by Carol Sakala on June 10, 2011 at 1:29 PM

Fifth of six submissions from Childbirth Connection:

Preventing Cesarean Deliveries
Childbirth Connection very much appreciates this focus and the inclusion of social/behavior/system factors. We encourage exploration of practice variation, assessment of the contribution of laborists (who do not have pulls to be elsewhere and might: retain a high level of skills and knowledge for childbirth within a relatively focused scope of practice, contribute to caregiver and woman satisfaction, reduce risk of liability, etc. - see Debra Gussman paper at http://www.oblaborist.org/studies.php). We also hope NICHD will explore ways of engaging childbearing women on this issue, notably through decision aids and the full complement of health information technologies.

VBAC is conspicuously absent in the statement in the White Paper. For the public's health, appropriate use of resources, ethics, and other reasons, it is unacceptable to walk away from VBAC, and we encourage NICHD to include this in its ongoing agenda. The 2010 consensus conference was a start, but much more is needed.

We have a special concern about cesarean section among larger women. Given the exceptional hazards of cesareans and repeat cesareans in this population, we need to understand how to minimize use of this intervention in women of size, versus the trend of extremely high cesarean section rates in this population.

We encourage a special focus on - borrowing from the breastfeeding world - protecting (avoiding disruption), promoting (policies, education, protocols, guidelines), and supporting (fostering labor progress - see Labor Progress Handbook) physiologic birth. Support women and fetuses to fulfill their innate capabilities for childbirth and thus reduce the cascade of intervention that often leads to cesarean section.

We encourage NICHD not to "reinvent the wheel," as there are many high-performing groups that have demonstrated the ability to achieve much lower-than-average cesarean rates among mixed-risk women. These often, but of course not always, involve midwives, and they often but not always involve out-of-hospital settings (birth centers, home). How can we bring the benefits offered by these high-performers to the general population of childbearing women and newborns? NICHD could learn much from partnership with American College of Nurse-Midwives, National Association of Certified Professional Midwives, and American Association of Birth Centers.

Submitted by Carol Sakala on June 10, 2011 at 1:34 PM

Sixth of six submissions from Childbirth Connection:

Pregnancy and Future Health
This section appropriately calls out cardio-metabolic dysfunction. We also encourage attention to (1) immune system issues (e.g., mode of birth and gut colonization, very high rate of exposure of this population to antibiotics), (2) shorter and longer term impact of infant feeding practices (whether, how long, how exclusive breastfeeding) on maternal and child health (see http://www.ahrq.gov/clinic/tp/brfouttp.htm), (3) effects of abdominal surgery on mothers (including implications of adhesions and scarring) and babies (including childhood chronic disease), (4) given the extent of exposure to such maternity interventions as pain medications, antibiotics, synthetic oxytocin, and ultrasound, careful examination of possible life course implications, including epigenetic effects, and (5) relationship between current second stages practices (e.g., supine position, forceful directed pushing, fundal pressure, episiotomy) and pelvic floor health. Longer term evidence is needed to understand possible effects of these common practices.

Placental Medicine and Syndromes
We encourage NICHD to include in this category the sequelae of cesarean section and repeated cesareans.

Preterm Birth
In addition to preterm birth, please include early term birth in investigations of trends, causes, consequences, and solutions due to developing evidence about implications for NICU admissions, respiratory problems, mortality, and developmental trajectories. What is the full range of implications?


Childbirth Connection stands ready and willing to partner with NICHD to work together on our shared aims of optimal care and outcomes of childbearing women and newborns.

Submitted by Carol Sakala on June 10, 2011 at 1:36 PM

The participant list was completely dominated by physicians who have created many of the problems in the maternity care system. They have rejected quality research that supports a less invasive approach to pregnancy and birth without negatively affecting outcomes for either mother or infant. The report cites a need to rely more on technology (electronic fetal monitoring systems) which has not been associated with improved outcomes among low risk women who comprise the majority of pregnancies. Looking to other industrialized countries with much better maternal and fetal outcomes one difference becomes clear. Licensed midwives can and do provide care that is cost effective, safe, and appropriate for many women. They appear to have been completely excluded from this project. Why?

Submitted by Marilyn Curl on June 10, 2011 at 2:03 PM

Nice summary of issues to address in pregnancy and affecting the outcomes of pregnancy.

Areas that did not appear to be addressed which should be include a focus on improving neonatal care and optimal interventions for the neonate, especially the preterm neonate. Were prematurity to be successfully prevented, as desired by the white paper and the NICHD, perhaps the latter will no longer be an issue; but until that is the case, optimal interventions and care for the preterm infant are needed.

The common theme of understanding the biology of pregnancy is crucial - however this is the type of work that study sections typically do not find exciting or innovative. Investigators who attempt to obtain funding generally do not fare well, so if it is an important area to develop, new methods to support this research will be needed.

The concept of integration of the biology of the fetus, placenta, mother across levels of investigation (genes through environment) is crucial, especially in the context of understanding disparities in perinatal medicine. However, these studies are incredibly complex and have also suffered from difficulties in study section.

The development of methods and tests for screening for conditions that will develop in pregnancy will benefit both those pregnancies and the development of interventions. This also requires well characterized pregnancies to ensure the definition of the condition is accurate. All of these are costly. Some of the recent and ongoing cohorts and trials supported by NICHD may be leveraged to address these questions, but would require a mechanism to facilitate these studies (in the ongoing cohorts) and the analysis of existing specimens in the completed studies/trials.

Obstetrics has clearly benefitted from the evidence provided by randomized controlled trials supported by the NIH - the guidelines for obstetric care by the professional bodies demonstrate their reliance on this data. The recommendation for additional trials on fetal growth restriction, preeclampsia, preterm birth and fetal therapy are crucial to further improve our care of women and their children and families (page 4).

(cont'd)

Submitted by Catherine Spong on June 10, 2011 at 2:15 PM

(cont's from prior)
The concept of using pregnancy as a predictor of long-term maternal health (page 4) is also gaining momentum. The NHLBI and NICHD held a workshop this past year on this topic and clearly there is evidence to support this idea. Were we to identify markers during prepregnancy that we would intervene on to prevent long-term maternal issues such as cardiovascular disease and diabetes, we could improve women's health and reduce health care costs. The opportunity to do this is present with well defined cohorts of pregnant women (eg the CAPPS trial of 10,000 women well phenotyped for pregnancy induced hypertension and preeclampsia; the GDM trial of women with mild GDM who were randomized to treatment or no treatment). What is needed is the opportunity to support follow up of these cohorts.
We have had success in the support for developing miniaturized devices for use in the NICU - additional work is needed to develop non-invasive devices to monitor the ongoing pregnancy including the developing fetus(es) and placenta(e). Were these available we may be able to address the common theme of understanding the biology of pregnancy.

Although not a research need, the paper did not appear to note the issue of malpractice and tort reform which likely are truly needed to be able to address the rising cesarean rate. Although the areas noted to address cesareans are clearly important and needed, it is likely that without tort reform even with these issues addressed the cesarean crisis will continue. This is clearly problematic given the implications and risks of multiple cesareans.


Statements that did not ring true include
Page 2: "....a general consensus that a restructured and re-energized research initiative was needed." The information in the white paper is not particularly different than what is in strategic plans, Council reports and workshop executive summaries from the Branch. Overall NICHD has specifically addressed these areas in numerous venues over the last decade.

Submitted by Cathy Spong on June 10, 2011 at 2:16 PM

The pregnancy and pregnancy outcomes white paper discusses very important research topics. However, the role of individual choice and the role of the health care system and its financing in determining pregnancy, its timing and its outcomes seems to not have received much attention. When the role of individual choice is mentioned, it is not highlighted and the importance of financial incentives is not mentioned. To take an example, the discussion of pregnancy and future health advocates use of cohort studies to characterize risk prior to conception. But the timing of conception and whether the ensuing pregnancy is wanted have been shown by social scientists to depend on aggregate and individual economic conditions (e.g., famine, the unemployment rate, whether one has lost one's job). Pregnancy outcomes have been shown to depend in part on maternal investments, which themselves may depend on financial incentives (e.g., costs of health care). Incorporating the insights and methods of social science and economics into the study of pregnancy and pregnancy outcomes would help advance knowledge.

Submitted by Marianne Bitler on June 10, 2011 at 2:26 PM

On behalf of the Guttmacher Institute, thank you for the opportunity to comment.

First, given the "mandate for cross-disciplinary interaction," we recommend that language be added to the paper on the importance of social science research on pregnancy and pregnancy outcomes. Demographers, psychologists and behavioral scientists, as well as those working in related disciplines, have made important substantive contributions to documenting and understanding pregnancy and pregnancy outcomes. Further work from these disciplinary perspectives and studies that integrate these perspectives with the medical and epidemiological perspectives is greatly needed and would bring important added value.

For example, some social scientists who study reproductive health have focused on measuring the important issue of the intention status of pregnancies, and their work shows that unintended pregnancies are very common: 49% of all pregnancies in the United States are unintended. Women who find themselves unexpectedly pregnant are less likely to engage in behaviors that are essential for achieving a healthy outcome for both themselves and the newborn. Moreover, the life course perspective endorsed in the White Paper is a methodological approach that is widely used and found to yield rich information, within the social sciences, where it was developed.

Second, throughout the White Paper the term pregnancy refers almost exclusively to births, even though a substantial minority of pregnancies ends in miscarriage and elective abortion (and, to a far lesser extent, stillbirths). At a minimum the White Paper should acknowledge that approximately one in five pregnancies is voluntarily terminated and one-third of women will have an abortion by age 45. Similarly, slightly fewer than one in five pregnancies ends in miscarriage. The White Paper suggests that future research needs to examine both short and long term maternal and fetal health outcomes: we endorse this and would add that it also needs to encourage cross-disciplinary, prospective studies of the full range of women's pregnancy outcomes. We recommend that the White Paper take a more comprehensive approach to the life course perspective, recognizing that the same woman can experience multiple pregnancy outcomes over the life course and, in turn, have different needs around pregnancy at different points in her life. In addition, more research on the causes and consequences of unintended pregnancies is greatly needed.

Submitted by Heather Boonstra on June 10, 2011 at 3:02 PM

Many aspects of pregnancy outcomes are the result of decision-making process that are affected by the economic environment. There is the decision to have get pregnant (or to not use contraceptives), how many times and at what age, in addition to decisions about whether to seek prenatal care, whether to smoke, drink or use drugs during pregnancy, and decisions about where to have the delivery (e.g. midwife or major hospital). All of these decisions can depend on demographic and economic factors, such as income, earnings opportunities, health insurance availability, place of residence and health provider availability, prices, and welfare policies within the state. There is also the separate decision by the doctor about whether to do Caesarian deliveries, which may depend on type of physician training and experience, reimbursement rates for those procedures and malpractice laws and insurance. If the focus is on understanding outcomes, there needs to be an understanding of these various decision processes in addition to the biological aspects of pregnancy. There is a relatively well developed economics literature aimed at modeling fertility decisions and outcomes as well as a smaller literature on modeling doctor decisions that would be helpful to consider here. There also needs to be rigorous assessment of costs and benefits of policies aimed at affecting pregnancy outcomes (such as changes to insurance contracts, to malpractice laws, to welfare policies, or to medical reimbursement rates). The social science aspects of pregnancy decisions and outcomes have not received much attention.

Submitted by Petra Todd on June 10, 2011 at 3:27 PM

Lactation is well understood to have positive long term benefits for both the mother and infant. The AAP and other organizations have set goals related to exclusive breastfeeding. The statistics are available from various resources on how these ideals are not yet being met. However, the research behind how to treat common problems associated with breastfeeding failure are lacking. Practitioners do not have access to the evidence-based information on how their treatment choices of the pregnant or post-partum women could effect the sucess of the breastfeeding dyad and ultimately the health outcomes of the mother and baby.

The Surgeon General calls for the development of a national consortium on breastfeeding research. The Call to Action states : "Such a consortium would help overcome the limitations that researchers now face in designing studies, increase the generalizability of research on breastfeeding, help prioritize key research areas, enable expanded and advanced research to be performed, and foster the timely translation of research into practice." NICHD should strongly consider leading the way with research in this arena.

Submitted by Charlita Atha on June 10, 2011 at 4:07 PM

The National Women's Health Network is a nonprofit women's health advocacy organization supported by our members - we do not take financial contributions from any entity with a financial stake in women's health decision-making.

We strongly agree that research is needed to improve healthy childbearing and birth outcomes in the U.S., which are among the lowest in the developed world, and to provide clinicians with evidence-based practices. We encourage NICHD to conduct research to reduce unnecessary interventions.

The vast majority of workshop participants agree that "cesarean deliveries increase the potential for long-term consequences to the health of the mother and her off-spring." Yet, today's caregivers are losing the skills needed to support physiological childbirth in some circumstances, such as vaginal breech, vaginal twins, and vaginal birth after cesarean (VBAC). We strongly recommend that NICHD help to ensure that caregivers have the knowledge and skills to support physiological childbirth, as well as examine the social, behavioral, and systems factors associated with elective cesarean delivery. We also recommend that NICHD conduct research on the high number of VBAC deliveries and encourage the Institute to reach out to groups that have demonstrated the ability to achieve much lower-than-average cesarean rates. These often involve midwives and out-of-hospital settings.

We also recommend facilitating interdisciplinary research to reshape the way clinicians approach preterm labor and birth. We appreciate NICHD's strong statement about eliminating preventable iatrogenic premature births. It is vital to reduce unnecessary labor induction or cesarean, which electively end uncomplicated pregnancies. While we agree that research should be done to develop preventive responses to known determinants of preterm labor, we also urge NICHD to conduct research to better understand preterm labor generally, including identifying additional determinants that might hold promise for successful preventive interventions. Lastly, we urge NICHD to host a State of the Science Conference to assess the clinical practices in use to prevent preterm labor and to discourage the use of techniques that have been found to have no effect or cause harm, such as the use of terbutaline.

Submitted by Kate Ryan on June 10, 2011 at 5:16 PM

. We believe that the following areas should be given priority:
*Understanding the genetic and epigenetic factors that play a role in successful pregnancy outcomes.
*Defining how environmental exposures impact pregnancy outcome.
*Developing and expanding animal and ex-vivo models to study mechanisms of disease and the basic physiology of pregnancy.
*Understanding the effects of nutrition (under and over) on pregnancy and the quality of life of the offspring.
*Leveraging opportunities from NIH initiatives such as the Children's Health Initiative.
*Providing cross-disciplinary training that includes toxicology.
*Participating in the development of searchable clinical databases that would enable assessment of changes in pregnancy and outcome.
*Studying data sets from other industrialized countries that have less adverse birth outcomes.
The document notes the importance of animal models, but does not delineate any examples of how they can be used. There is a failure to delineate the use of animal models to study mechanisms of disease that could lead to new biomarkers. Likewise, we believe that there is a need to study the effects of nutrition and other metabolic diseases. Also, we suggest that while the emphasis of the paper is purely on relevant research, there is a lack of age- and stage- specific preclinical safety data for chemicals and drugs as it would pertain directly to the most pressing health concerns in pregnant women and their children. To be truly effective, research and safety testing needs to move forward together in similar health risk reduction priorities and we hope this point is not lost in the territorial divisions among agencies. The document does recognize the importance of the placenta and the mother/placenta/fetal interaction, but fails to suggest how these interactions could be further explored, other than evaluating existing human data sets.

Submitted by Martha Guest on June 10, 2011 at 5:22 PM

Although there is a body of research on breastfeeding, significant knowledge gaps are evident. These gaps must be filled to ensure that accurate, evidence-based information is available to parents, health care providers, public health programs, and policy makers.

The Surgeon General's Call to Action to Support Breastfeeding calls for increased funding of research on breastfeeding (Action 17) and strengthened capacity for conducting research on breastfeeding (Action 18).

Specifically the Surgeon General calls for the development of a national consortium on breastfeeding research. The Call to Action states : "Such a consortium would help overcome the limitations that researchers now face in designing studies, increase the generalizability of research on breastfeeding, help prioritize key research areas, enable expanded and advanced research to be performed, and foster the timely translation of research into practice."

We encourage NICHD to take the lead on this action by developing a platform for a national consortium of researchers interested in breastfeeding research.

Submitted by Megan Renner on June 10, 2011 at 11:44 PM

The period for commenting on NICHD scientific Vision white papers is now closed.

Last Updated Date: 06/04/2012
Last Reviewed Date: 06/04/2012