We review three decades of unsuccessful efforts by public policy-makers in the United States to develop programs to lower the rate of preterm birth. We analyze why these efforts had been unsuccessful. Finally, we will speculate about whether something has changed in the last few years that might finally bend the curve and reverse the trend of a steadily rising preterm birth rate. In 2007 and 2008, the rate of preterm birth in the United States dropped. This was the first time that the rate had dropped for 2 years in a row in over 30 years. The first drop was quite small—from 12.8% in 2006 to 12.7% in 2007—so public health officials were cautious about whether this was the start of a trend. But the second drop was larger—from 12.7% to 12.3%—and made it seem as if 30 years of efforts to lower the rate of preterm birth might finally be paying off. Still, questions remained. Why did preterm birth rates continue to rise so inexorably for so long? What led to the recent declines? Can the momentum be maintained, so that preterm birth rates continue to drop?In order to examine what is behind these trends, we will review three decades of efforts by public policy-makers to develop programs to lower the rate of preterm birth. We will then examine some explanations for why these efforts had been so unsuccessful. Finally, we will speculate about whether something has changed in the last few years that might finally bend the curve and reverse the trend of a steadily rising preterm birth rate. We will talk only about preterm birth in the United States. Other industrialized countries have seen generally similar trends, for similar reasons, with some local variation. The situation in developing countries is very different.First, we want to be clear about the terms we will be using, because many policies and outcome studies use different measures. In analysis of perinatal outcomes, the terms “preterm birth” and “low birth weight” are sometimes used almost interchangeably. Preterm birth is defined as birth before 37 weeks of gestation, measured from the first day of the pregnant woman’s last menstrual period. Low birth weight is defined as a weight less than 2,500 grams or about 5.5 pounds. Some babies are low-birth-weight without being preterm. Others are preterm but not low-birth-weight. Birth weight is easier to measure accurately than is gestational age. Thus, much data and many policies focus on low birth weight because accurate gestational ages are often not available.For the 30 years prior to 2007, practitioners and policy-makers seemed powerless to reduce—or even stabilize—the rate of preterm birth in the United States. Between 1980 and 2006, the percentage of births that were preterm rose from 9.4% to 12.7%—a rise of nearly 30%.2Low birth weight is a major determinant of infant mortality in the United States … In addition to increasing the risk of mortality, low birth weight also increases the risk of illness … The association of neurodevelopmental handicaps and congenital anomalies with low birth weight has been well established; low birth weight infants also may be susceptible to a wide range of other conditions, such as lower respiratory tract infections, learning disorders, behavior problems, and complications of neonatal intensive care interventions.3The failure to reduce the rate of preterm birth over these years was not for lack of effort. Like a drum-beat, national commissions periodically recognized and highlighted preterm birth as a significant medical and public health problem. Their reports invariably set ambitious goals of reducing preterm birth or low birth weight in the foreseeable future and recommended concrete mechanisms for achieving those goals. One of the first of such reports, from the Institute of Medicine (IOM) in 1985, was entitled “Preventing Low Birth Weight.” That report laid out the stark facts:The report argued that better access to prenatal care would lower the rate of low birth weight and preterm birth, and that programs to improve access to prenatal care would be cost-saving. It argued for the following causal chain: 1) poor people who did not have health insurance were without access to prenatal care; 2) programs to provide insurance to poor people would lead to higher rates of prenatal care; 3) higher rates of prenatal care would lead to lower rates of preterm birth; 4) lower rates of preterm birth would mean less need for expensive neonatal intensive care, which was already paid for by government insurance programs; therefore, 5) increased access to prenatal care would lead to a net cost saving for government insurance programs. The IOM estimated that every dollar spent on prenatal care would save $3.37 in neonatal care expenses. This led one legislator to conclude: “It is not often that a person in public life gets to say, ‘I know how to save the lives of American children and save taxpayer money at the same time’.”4In response to this report, the United States Congress passed legislation in the late 1980s that provided funding to expand the Medicaid program—a government health insurance program for the poor—in order to increase the number of poor women eligible for free access to prenatal care. This legislation had bipartisan congressional support and was signed into law by Republican President George W. Bush.In one sense, these Medicaid expansions worked. More women did, in fact, enroll in Medicaid, and more of these women received prenatal care. From 1990 to 2003, the percentage of women who enrolled in prenatal care during the first trimester of pregnancy increased. The increases were largest in the highest-risk groups—7% for non-Hispanic white women, 24% for non-Hispanic black women, and 29% for Hispanic women. The percentage of pregnant women who did not receive any prenatal care was cut in half.5In another sense, however, the policies seemed to be a dismal failure. National rates of both preterm birth and low-birth-weight birth continued to rise.Healthy People 2000, setting 10-year goals for the nation’s health. One of the goals was to reduce the rate of low-birth-weight births from 6.9% to 5%. Over the ensuing decade, the rate rose from 6.9% to 7.6%.Healthy People 2010, calling once again for a goal reducing low birth weight to 5%. In addition, this report called for a reduction in preterm birth from 11.6% to 7.6%. Over the next years, both low birth weight and preterm birth continued to rise.In 1991, the Surgeon-General of the United States issued a report, Infants born preterm are at greater risk than infants born at term for mortality and a variety of health and developmental problems. Complications include acute respiratory, gastrointestinal, immunologic, central nervous system, hearing, and vision problems, as well as longer-term motor, cognitive, visual, hearing, behavioral, social-emotional, health, and growth problems. The birth of a preterm infant can also bring considerable emotional and economic costs to families and have implications for public-sector services, such as health insurance, educational, and other social support systems. The annual societal economic burden associated with preterm birth in the United States was at least $26.2 billion in 2005.7In 2007, the IOM issued a follow-up to its 1985 report. Once again, they presented the compelling case for a new national effort to reduce the rate of preterm birth. They noted:The next year, the Surgeon-General of the United States echoed the IOM’s call for more attention and research on the problem of preterm birth.preventive intervention. It was assumed that, if women got timely and comprehensive prenatal care, they would be less likely to deliver a baby too soon or deliver one that was too small. This belief persisted, even as evidence accumulated that improved access to and utilization of prenatal care did not reduce the rate of preterm or low-birth-weight births. As a preventive measure, prenatal care was clearly not working the way it was supposed to work.Over all these years, and in most of these reports, the fundamental analysis and understanding of the basic nature of the problem of preterm birth and the consequences of such births have remained largely unchanged. Prenatal care was seen as a fundamentally Broadly speaking, there are three sorts of explanations for the trends in preterm birth rates. One explanation is that the interventions that we have used to try to lower the rate of preterm birth—primarily, the interventions that collectively are known as prenatal care—simply do not work. By this view, prenatal care itself needs to be redesigned to include only evidence-based interventions. Some recent reviews carefully evaluate various components of prenatal care in order to determine what actually works.Another explanation for rising rates of preterm birth is that changes in the demographics of childbearing in the United States (and most of the developed world) have led to more high-risk pregnancies than ever before. Specifically, more women are delaying childbearing until they are in their 30s or 40s. Older women are known to have higher rates of both infertilityA third, related, explanation for the rise in preterm birth rates is that the rise is driven by medically induced preterm births—either by C-section or by pharmacologic induction of labor. This, then, leads to debates about whether such medical inductions are necessary or beneficial. Many critics of modern obstetrics see these medically induced preterm births as unnecessary and harmful. Others think that many, perhaps most, medically induced preterm births are beneficial.preventive treatment and more an intervention designed to identify and respond to problems that threaten the health of fetuses.We offer a fourth explanation, one that is related to and intertwined with the others. It may be that both the process and the outcomes of prenatal care have been misunderstood. It may be working, but working in a different way than it was once thought to work. Often, today, prenatal care allows the diagnosis of fetal problems or of maternal conditions that put the fetus at risk. Such diagnoses may lead to a medically induced preterm birth. When done appropriately, medically induced preterm births can lower the rate of both stillbirth and neonatal morbidity and mortality.We will discuss each of these explanations and show how they might each be a part of the story. Finally, we analyze the implications of these analyses.In the 1980s, the conventional wisdom was that better access to prenatal care would lead to lower rates of preterm birth and lower costs. The studies that led to this conventional wisdom generally compared women who received little or no prenatal care with women who received adequate prenatal care. In those studies, the women who received adequate prenatal care had dramatically better outcomes. For example, Leveno and colleagues published such an analysis in 1985: “Women seeking prenatal care had a significantly decreased incidence of low birth weight infants compared with those without such care … Prenatal care was associated with a 50% decrease in costs for each infant.”13P<0.001) including an antenatal charge of $600 in the Comprehensive Perinatal Program. The excess cost for delivery of 400 women receiving no care per year in the study hospital was $877,600.14When the total inpatient hospital charges were tabulated for each mother-baby pair, the cost of perinatal care for the group receiving no care ($5168 per pair) was significantly higher than the cost for patients in the Comprehensive Perinatal Program , the use of community health centers and maternal and infant care projects, abortion, prenatal care, and neonatal intensive care. Their primary outcome measure was dollars (1984 dollars) per life saved. They showed that prenatal care was the most cost-effective of all these interventions, with a cost of about $30,000 per life saved. By contrast, neonatal intensive care, by their estimates, cost over $2 million per life saved.15These studies defined the conventional wisdom. But the policies that they engendered did not lead to the expected outcomes.Dubay and colleagues analyzed the effect of these expansions in the Medicaid program on access to prenatal care and birth outcomes. After the expansions, more women enrolled in early and comprehensive prenatal care. But there was no decrease in the rate of low birth weight. The researchers concluded: “The emerging lesson from the Medicaid expansions, however, is that increased access to primary care is not adequate if the goal is to narrow the gap in newborn health between poor and non-poor populations.”16Ray and colleagues studied the effect of Medicaid expansions in Tennessee. They concluded: “In Tennessee, the Medicaid expansions materially increased enrollment and use of prenatal care among high-risk women, but did not reduce the likelihood of preterm birth.”18An insightful 1994 essay by Huntington and Connell suggested why. They pointed out that most of the earlier studies showing that prenatal care would be efficacious and cost-saving had serious methodologic flaws.In response, researchers and practitioners developed and tested new and innovative ways to deliver more comprehensive prenatal care to the highest-risk women. They carried out randomized trials of different combinations of prenatal interventions. The programs included better social support, consultation with expert nutritionists, smoking cessation programs, stress reduction, subsidized transportation to clinic, comprehensive screening for vaginal and cervical infections, and other interventions. The goal of these studies was to come up with the absolute ideal of comprehensive prenatal care for the women at highest risk for bad outcomes. In short, they tried to both define a new approach to prenatal care and propose that it become the standard of care.Although observational and quasi-experimental studies have produced a large volume of circumstantial evidence supporting the notion that comprehensive, multicomponent prenatal care prevents low birth weight, studies employing rigorous investigative methods have consistently failed to confirm the efficacy of this intervention strategy.20Eight such trials were summarized by Stevens-Simon in a 1999 meta-analysis. Overall, the trials enrolled nearly 10,000 pregnant women. Women who were offered psychological counseling, nutritional counseling, transportation, social support, comprehensive medical screening, and state-of-the-art obstetric services were compared with women who were offered “standard” prenatal care. Stevens-Simon concluded:Lu and colleagues did a similar analysis.Perhaps one of the reasons why prenatal care did not work as well as it had been predicted to work was because pregnancy itself was changing. In particular, there is some evidence that the changing demographics of childbirth have led to more and more high-risk pregnancies.in-vitro fertilization. Both older maternal age and assisted reproduction are associated with higher rates of preterm birth.Over the last three decades, as prenatal care programs were expanding and preterm birth rates were rising, the demographics of childbearing were also changing. Two particular changes were noted. First, the widespread availability of safe and effective contraception—along with social changes—led many women to delay childbearing into their 30s or 40s. Second, more and more women with infertility problems were using ovarian stimulatory drugs or first pregnancy increased by nearly 4 years between 1968 and 2002, from 21.4 to 25.1 years of age. The mean age at childbearing for all pregnancies rose over those years from 24.9 to 27.3. Over those years, the percentage of first births to women over 35 years of age went from less than 1% to 4%.22Since 1970, the fertility rate has gone steadily down for women under 30 and steadily up for women over 30. The average age at childbearing has been rising for the last 50 years. The mean age of women at the time of their in-vitro fertilization.in-vitro fertilization have leveled off.26Delaying childbearing is associated with higher rates of infertility.But these are not the only changes in the demographics of childbearing over these years. There has been a large increase in the percentage of births to unmarried women. This trend has been apparent since at least 1940, when only about 5% of births in the United States were to unmarried women. In 2007, 40% of births were to unmarried women.In 2007, fertility rates were highest for Hispanic women  and lowest for non-Hispanic white women .We analyzed the effects of these changing demographics on overall rates of preterm birth, and showed that, taken together, these shifts in demographics cancel each other out as explanations for rising preterm birth.Obstetrics is clearly changing. Perhaps the most easily measurable indicator of the changes in obstetrics over the last 40years is the rate of C-sections. In 1970 in the United States, 5.1% of deliveries were by C-section. By 1980, C-sections were performed in 16% of all deliveries. The rate leveled off between 15% and 22% in the 1980s and then began to rise dramatically once again. By 2006, it reached 31% of deliveries.Many C-sections are done preterm, and the rate of C-sections in preterm births has been rising along with the rate in term births. In 1991, 25% of singleton preterm births were by C-section. By 2006, the percentage had risen to 36.9%. Over these years, C-section rates rose in all age groups, in all racial groups, and among women with all different types of health insurance, including no insurance. C-section rates rose as fast among women with no identifiable risk factors as among high-risk women .32Is this necessarily a bad thing? The answer is not so clear. Some argue that medically induced preterm deliveries are preventing intrauterine fetal deaths, particularly fetal deaths in the third trimester of pregnancy. The data to support such claims come from epidemiologic studies of associations between medically induced preterm birth and fetal death rates.Over the last few decades, fetal death rates have fallen dramatically in the United States. In 1985, the fetal death rate was 7.8/1,000 pregnancies. By 2004, it had declined to 6.2/1,000, a 20% drop. The drop in late fetal deaths, those after 27 weeks of gestation, was even more dramatic. Rates fell from 4.95/1,000 to 3.1/1,000, a 37% drop.34Fetal mortality rates (after 20 weeks of gestation) and neonatal mortality rates (up to 28 days of age) can be combined into a “perinatal mortality rate.” That has fallen from 14.6/1,000 live 20-week fetuses in 1985 to 10.7/1,000 in 2004, a 27% drop.What accounts for this decline in fetal mortality, which is greatest after 28 weeks of gestation? According to a recent analysis by the Centers for Disease Control, much of the decline can be attributed to improved access to prenatal care leading to better fetal screening and the early diagnosis of pregnancy problems. The report highlights “fetal imaging, prevention of perinatal infections, effective treatment of maternal medical conditions such as diabetes and chronic hypertension, and more aggressive management of labor and delivery” as likely contributors to improved fetal survival.35Such an analysis might explain, in part, the relationship between improved access to prenatal care, decreased rates of fetal demise, and increased rates of preterm birth. For women in high-risk groups—categorized either demographically or medically—more intensive prenatal care with more frequent screening of both the pregnant woman and the fetus may lead to earlier diagnosis of medical risk factors or fetal distress. This, in turn, might lead to a clinical decision to induce delivery.Under the traditional model of perinatal death, neonatal deaths occur among infants in the first month after birth and the unborn fetus is not a candidate for neonatal death. However from a broad biological, obstetric and ultimately epidemiologic point of view, a fetus at any gestation is at risk of stillbirth and neonatal death at that gestation. If one considers a woman at 28 weeks gestation with severe preeclampsia and fetal compromise, the risk of stillbirth is easy to conceptualize. The risk of neonatal death is substantial as well and can follow either premature labor or medically indicated delivery. The same risks apply in concept to a woman with a healthy pregnancy at 28 weeks gestation, despite the magnitude of the risks being considerably smaller. Thus, although neonatal deaths literally occur among infants, fetuses can be considered candidates for neonatal death as well.36Joseph has used such data to propose a new theory of obstetrics. He argues the efficacy of obstetrics should be assessed by evaluating outcomes for all fetuses at risk—that is, all fetuses at 20 weeks of gestation or above.Lisonkova and colleagues analyzed pregnancy outcome data in the United States and Canada, using this approach, and showed that higher rates of medically induced preterm births were associated with decreased fetal mortality, infant mortality, and severe neonatal morbidity.37Such data suggest that the rise in preterm birth may not be such a bad thing. It may reflect better obstetrical care with more sensitive assessments of fetal distress. When coupled with excellent neonatal intensive care, it may lead to improved outcomes for babies compared to an approach to obstetrics that is oriented towards maximizing rates of term birth.Some have raised concerns, however, about the over-use of medically induced preterm birth, the consequent rise in near-term deliveries, and the morbidity associated with near-term birth, even when excellent neonatal care is available. For example, Woythaler and colleagues studied neurodevelopmental outcomes at 2 years for babies born after 37 weeks and those born between 34 and 37 weeks (“late preterm”). They showed that the late preterm babies had more physical, cognitive, and developmental delay.in-utero, after 20 weeks of gestation). They summarize these gains:Over the more recent period, 1990 to 2001, the IMR  declined 26 percent  for an average decrease of 3 percent per year. Between 1990 and 2001 the neonatal mortality rate declined from 5.8 to 4.5 per 1,000 (down 22 percent). Between 1990 and 2001, the late fetal mortality rate declined fairly steadily, by 23 percent, from 4.3 to 3.3 per 1,000. Although the pace of decline has slowed somewhat since the mid-1990s, significant declines in late fetal mortality and infant mortality have been observed through 2001 despite substantial increases in preterm and low birth weight risk, two important predictors of perinatal health.40Overall, this review suggests a complex relationship between changing demographics, changes in prenatal care and obstetrics, fetal mortality and infant mortality. Some of the changes in the demographics of childbearing—particularly delayed childbearing and increased average maternal age—clearly lead to more high-risk pregnancies. Other changes, such as increases in the education levels of pregnant women, lead to fewer high-risk pregnancies. Changes in obstetrics that make the management of high-risk pregnancies better inevitably spill over into obstetric practice generally. These changes make it possible to monitor the fetus more closely and to diagnose more fetal problems. It is hard to know which babies will benefit from medically induced preterm birth and which will not. Overall, we see infant and fetal mortality rates going down, even as preterm birth rates rise.These paradoxical results suggest that our way of thinking about the associations between prenatal care, preterm birth, and infant mortality may no longer accurately reflect epidemiological, medical, or social realities. Lower preterm birth rates may no longer be the best measure of the efficacy of prenatal and perinatal care. Instead, the best measure may be a combination of the rates of preterm birth, infant mortality, and fetal death.What are the implications of this analysis for predicting future trends in preterm birth rates? These multiple factors do not allow an easy answer to the question of the optimum mix of antenatal monitoring, interventionist obstetrics, and traditional midwifery approaches to achieve the best possible outcomes. Overall, though, it seems clear that the goals set out by public health authorities in the 1980s and 1990s—for preterm birth rates of 5% and C-section rates of 15%—are probably not optimum. Given current scientific knowledge, they would only be achievable at the cost of rising rates of fetal death or infant mortality. But will the rate of preterm birth continue to rise? That, too, seems unlikely. The recent drops in preterm birth rates in the United States may reflect a new equilibrium, in which advances in prenatal diagnosis, obstetric care of high-risk pregnancies, and neonatal intensive care, along with a new steady state in the demographics of childbearing, and more careful use of assisted reproductive technologies all combine to lead to an optimum balance between reproductive freedom, obstetrical intervention, and perinatal outcomes.


Low birth weight followed by accelerated weight gain during early childhood has been associated with adverse metabolic and cardiovascular outcomes later in life. The aim of this study was to examine the impact of early infant weight gain on glucose metabolism and cardiovascular risk factors in adolescence and to study if the effect differed between adolescents born small for gestational age (SGA) vs. appropriate for gestational age (AGA).P for interaction = 0.03). No significant associations were seen between postnatal weight gain and body composition or parameters of glucose metabolism assessed by the simplified intravenous glucose tolerance test. In subgroup analysis, all associations with early infant weight gain were absent in the AGA group, but the associations with basal insulin and HOMA-IR were still present in the SGA group.Data from 30 SGA and 57 AGA healthy young Danish adolescents were analysed. They had a mean age of 17.6 years and all were born at term. Data on early infant weight gain from birth to three months as well as from birth to one year were available in the majority of subjects. In adolescence, glucose metabolism was assessed by a simplified intravenous glucose tolerance test and body composition was assessed by dual-energy X-ray absorptiometry. Blood pressures as well as plasma concentrations of triglycerides and cholesterol were measured. Early infant weight gain from birth to three months was positively associated with the fasting insulin concentration, HOMA-IR, basal lipid levels and systolic blood pressure at 17 years. There was a differential effect of postnatal weight gain on HOMA-IR in AGA and SGA participants (This study suggests that accelerated growth during the first three months of life may confer an increased risk of later metabolic disturbances – particularly of glucose metabolism – in individuals born SGA. Small size at birth is associated with a range of metabolic diseases in adulthood, including type 2 diabetes, hypertension, and dyslipidemia per se. Catch-up growth may be due to the fetus having escaped an adverse intrauterine environment and may represent a major adaptive mechanism with independent late consequences The effect of postnatal growth on later health and disease depends to a high extent on birth weight. Indeed, rapid postnatal growth may have adverse effects on later health particularly in individuals born small for gestational age (SGA)rd trimester, was associated with insulin resistance and cardiovascular risk factors in adolescence We have previously shown that low birth weight for gestational age, but not restricted fetal growth in the 3This study was performed according to the Helsinki II declaration and was approved by the local ethics committee for Copenhagen and Frederiksberg (KF 01-229/02 & KF 01-065/03). Informed consent was obtained from all participants and from the parents when the participant was under 18 years of age.In a randomised controlled trial performed in 1985 to 1987 th percentile (−0.39 SDS/28 days). SGA was defined as birth weight SDS below the 10th percentile (-1.28 SDS), and AGA was defined as birth weight SDS above this cut-off. The relationships of FGV and IUGR with insulin resistance and associated cardiovascular risk factors in adolescence have been published elsewhere The study design is shown in Follow-up examinations were performed at 3, 6 and 12 months on half of the cohort n = 27) for the calculation of infant weight gain from birth to one year was collected by questionnaire. In total, 87 individuals  had data on weight SDS at three months and/or at one year and were included in the analyses. Of these, 57 were AGA and 30 were SGA (P = 0.574). There were no statistically significant differences in the measured outcomes at follow-up between individuals with postnatal growth data and those without.A total of 547 offspring were traceable, and among these 271 were invited to participate  . The stuwere SGA , Table 1Validated questionnaires One subject (AGA) was excluded from all analyses because of a diagnosis of type 1 diabetes. Polycystic ovary syndrome had previously been diagnosed in one girl; she was included in the analyses; exclusion did not alter the results.The experimental protocol has been described in detail previously Female participants who did not use oral contraceptives (n = 29 of 71) were examined at day 2 to 5 of their menstrual period.Blood samples for measurement of plasma insulin were centrifuged immediately at 4°C and stored at −20°C until plasma insulin concentrations were determined by the AutoDELPHIA Time-resolved Fluoroimmunoassay  . Plasma glucose concentration was measured using the Hexinase/G6P-DH-Determination  . Plasma triacylglycerol and cholesterol  were measured using an enzymatic absorption photometric method  (CV<5%).birth to 3 months) was calculated as ((weight SDS3 months – birth weight SDS)/ (age at measurement))*91 days. Infant weight gain from birth to one year (ΔWSDSbirth to 1 year) was calculated as: ((weight SDSone year – birth weight SDS)/(age at measurement)*365 days. For those who were not measured at one year in the original trial, we used a measurement of weight between 11 and 13 months (both months included), if reported in the questionnaire.Infant weight gain from birth to three months  (slope of log glucose concentration10–40 min), and insulin sensitivity (SI) . Disposition index (DI), representing insulin secretion corrected for the ambient degree of insulin resistance, was also calculated (SI×Δ insulin area0–10min). Furthermore, mean basal glucose , mean basal insulin  and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated According to the methods described by Galvin birth to 3 months and ΔWSDSbirth to 1 year on later health were analysed separately. All multiple linear regression analyses were adjusted for sex. Effects of post-natal growth on fat and lean body mass were adjusted for current weight, and effects of post-natal growth on blood pressure were adjusted for height and age. Age at examination and the use of oral contraceptives were not included in the analyses, because preliminary analyses showed that inclusion of these variables did not alter the results. Further adjustments for current BMI, fat mass and fat percentage were performed, each in separate analyses. Using general linear models with interaction terms between early infant weight gain and AGA/SGA status, we determined whether the effects of early infant weight gain on later health differed significantly between the SGA and AGA groups. Individuals born AGA and SGA were compared to each other using Students t-test for the continuous variables and Chi2-test for frequencies. All statistical analyses were performed using the statistical package SPSS .Dependent variables that did not fulfil the assumption of normality were logarithmically transformed, which in all cases gave distributions close to normal. Effects of ΔWSDSP<0.0001; Individuals in the SGA group had lower birth weight SDS (in agreement with the classification), and higher absolute early infant weight gain from birth to three months and to one year . At one birth to 3 months was positively associated with basal insulin concentration and HOMA-IR, as well as with plasma triglyceride, total cholesterol, LDL, and systolic blood pressure at adolescence  (P = 0.05).In the entire group, ΔWSDSlescence . Furtherfat mass . Of the birth to 3 months in the SGA and AGA on both HOMA-IR . In the SGA group, the association of ΔWSDSbirth to 3 months with basal insulin levels and HOMA-IR was positive (birth to 3 months) with HOMA-IR remained significant in the SGA group (P<0.05). ΔWSDSbirth to 1 year was also positively associated with HOMA-IR in the SGA group (P = 0.02). In the AGA group, early infant weight gain from birth to three months .In this prospective study we observed a relationship of early infant weight gain from birth to three months with glucose metabolism, lipid profile, fat mass and systolic blood pressure in adolescence. Interestingly, the associations to glucose metabolism were only apparent in adolescents born SGA, supporting that catch-up growth is adversely associated with disturbances of glucose metabolism later in life, while accelerated weight gain in infants born AGA does not seem to be particularly detrimental for glucose metabolism in adolescence. Our finding that early infant weight gain had different effects on glucose metabolism but similar effects on lipid profile and blood pressure among the SGA and AGA groups is novel, and support a growing awareness of differential trajectories and mechanistic pathways of the influence of pre- versus post-natal growth on the development of diabetes, stroke and coronary heart disease et al. found that rapid growth during the first 3 months of life was associated with insulin resistance and markers of cardiovascular disease in young adults independent of birth weight SDS th century, whereas overfeeding has become more common during recent years. Therefore, it may be speculated that in cohorts of people born in the 1930–1940's, the adverse metabolic programming could potentially occur at a later time during childhood than in the cohorts born in the 1980–1990's.Other studies have shown adverse effects of accelerated early infant growth on glucose metabolism in infants and children born SGA. These findings include increased basal insulin levels associated with growth of weight between birth and one year Adiposity seems to play a major role in the association between low birth weight, childhood growth and adult disease et al. infused daily doses of long-acting insulin or saline from the 8th to the 11th day of life in Wistar rats Previously, we showed in this cohort of adolescents that being born SGA was associated with a wide range of markers of the metabolic syndrome rd trimester. Thus, paradoxically, growth in the first three months after birth seems to be more important than growth in the last three months before birth. This suggests that birth in itself opens a new window of sensitivity to metabolic programming, perhaps as an adaptive response to the change of environment. Efforts to alter the postnatal environment, i.e. to restrict early infant weight gain in SGA individuals, have hitherto not been recommended. Weight gain during the first months after birth is influenced both by the mode of feeding and the amount of energy eaten. A systematic review has shown that breastfeeding is associated with a reduced risk of type 2 diabetes later in life In a previous publication In conclusion, we found that accelerated growth during the first three months of life was associated with later metabolic disturbances – particularly of glucose metabolism – in individuals born SGA. Our findings thereby support the idea that the very early postnatal period is a critical window for individuals who have experienced a growth insult in fetal life.


It is suggested that impaired fetal growth can affect kidney development, resulting in fewer glomeruli being formed and reduced kidney function later in life. The aim of this study was to investigate early life variables in relation to adult kidney function, and compare these to the influence of later life variables.Detailed information was collected prospectively regarding 1,142 babies, born in 1947 in Newcastle upon Tyne. At the age of 63–64 years, 335 participants had serum creatinine successfully measured and completed a lifestyle questionnaire. These measurements were used to calculate their estimated glomerular filtration rate (eGFR).Body mass index (BMI) and being female were significantly negatively associated with eGFR. Birth weight was significantly positively associated with eGFR. In sex-specific analyses, BMI and cigarette smoking remained significant for males (n = 154), with a near significant association for birth weight, whereas none of the variables remained significant for females (n = 181).The findings suggest that sex, size at birth and BMI may be important variables influencing adult kidney function. However, as only a small amount of variance in eGFR was explained by these variables, additional longitudinal studies would be beneficial for assessing lifecourse influences on kidney function. It has been estimated that 1 in 10 people in the United States A number of studies have found a positive association between birth weight and eGFR Further, little research has been done to investigate the impact of other early life influences in relation to adult kidney function such as socio-economic status (SES) and breastfeeding. Research into the associations between later life influences and kidney function have shown conflicting results for body mass index (BMI) The study received ethical approval from the Sunderland Local Research Ethics Committee and all study members gave their written consent.ad hoc basis by the study team, which consisted of health visitors (nurses who visited families at home) and paediatricians.The Newcastle Thousand Families study began as a prospective study of all 1142 children born in May and June 1947 to mothers resident in Newcastle upon Tyne, in northern England The cohort underwent a major follow-up at age 49–51 years Information on early life was recorded prospectively for all study members The number of cigarette pack-years smoked (one pack-year represents one pack of 20 cigarettes smoked per day for one year) were estimated from the responses to the questionnaires at age 49–51 years  and 63–64 years. Four categories of alcohol consumption at age 49–51 years were derived from responses to the age 63–64 questionnaire: No drinking; light drinking ; moderate drinking  and heavy drinking . In the United Kingdom, one unit is 10 ml or 8 g of pure alcohol. SES at age 49–51 years was based on the occupation of the main wage earner in the household, according to the 1990 United Kingdom Registrar General's Standard Occupational Classification. This was used rather than at age 63–64 years by which time retirement or semi-retirement may make occupation-based measures of SES meaningless. The questionnaire included a section on self-reported medication use, the responses to which were used to identify participants taking angiotensin converting enzyme inhibitor (ACEI) medication, primarily due to high blood pressure.Height and weight were measured by research nurses, at the clinical assessment at age 63–64 years, and BMI derived. Kidney function was assessed by estimation of GFR, with low eGFR being indicative of poor kidney function, from the fasting serum creatinine measurements (μmol/L) recorded during the clinical assessment. Serum creatinine was divided by 88.4 to convert into mg/dL, in order to use in the GFR estimation which followed the Modification of Diet in Renal Disease equation SES, sex, housing grade and duration breastfed were treated as categorical variables. All other explanatory variables were treated as continuous linear variables. Representativeness of the participants in this study compared to the remainder of the original 1947 cohort was assessed using chi-squared tests for categorical variables and t-tests for continuous variables.2) was estimated, to indicate how much variation in eGFR was due to the variables in the model. Interactions were tested within the regression modelling framework. Statistical analysis was done using the statistical software package, Stata version 11.0.Univariate linear regression was initially used to test for associations between independent variables and the dependent variable, eGFR, followed by multivariable models for adjusted analyses. The coefficient of determination  and SES at birth (p = 0.001). In the original cohort there were more males compared to females; however, more females compared to males returned for the recent follow-up study. The percentage of people who were born in SES 1 remained similar; however, this value was higher for SES 2 and lower for SES 3. No significant differences were found for the remainder of the variables tested (p>0.05).2 (interquartile range (IQR) 22). Thirty six (11%) of included participants self-reported use of ACEI medication. This was not significantly associated with eGFR (p = 0.23).Continuous data used in the study are summarised in 2 reduction in eGFR in the adjusted model. Birth weight was positively associated with eGFR (p = 0.016), and a 1 kg increase in birth weight was associated with an estimated 3.85 mL/min/1.73 m2 increase in eGFR. There was no evidence of non-linearity in this association. However, there was not a significant association with birth weight when standardized for gestational age and sex or when comparing between low and normal birth weights. The number of cigarette pack-years smoked was positively associated with eGFR with each additional pack-year associated with an estimated increase in eGFR of 0.14 mL/min/1.73 m2. Contemporary BMI, was the most significant factor affecting eGFR independently (p = 0.001), and a 1 kg/m2 increase in BMI was associated with a 0.047 mL/min/1.73 m2 estimated decrease in eGFR. Adjusting for ACEI medication use made little difference to the results. The model containing the significant variables explained 8.7% of the variation in GFR in this cohort. There were no significant interactions for any of the variables tested, including between either birth weight or low birth weight and eGFR (p>0.05).Significant univariate associations with eGFR were seen for sex, birth weight, current smoking status, pack-years of cigarettes smoked, alcohol consumption and BMI , with se2 6.0%) had a twofold increased contribution to eGFR in comparison to the contribution from birth weight (R2 3.1%).In sex-specific analyses, BMI and cigarette smoking remained significant for males (n = 154), with a near significant association for birth weight . No variIn this study of data from the Newcastle Thousand Families birth cohort, there were significant associations between eGFR and BMI, birth weight and pack-years of cigarettes smoked. However, these findings were limited to the males within the cohort, albeit of only borderline significance for birth weight; with no significant associations seen in females.The result that a lower birth weight was significantly associated with a lower eGFR is consistent with the hypotheses put forward by Barker Very few of the included study members had birth weights below 2.5 kg. This may make our findings more relevant to the entire birth weight range, rather than in studies focussing on comparisons between low and normal weight births, If the mechanism is through nephron number, this is consistent with the finding of a positive correlation between birth weight and number of nephrons, across the birth weight range The sex differences seen in this study are similar to previous reports from the cohort in terms of sex differences in lifecourse predictors of chronic disease biomarkers The findings of a negative association between eGFR and BMI is consistent with some previous studies There have been conflicting reports into the effect of smoking on eGFR. In agreement with the results of this study, a number of studies have reported that cigarette smoking is associated with higher eGFR No associations with eGFR were found for SES at birth or at age 50 years. While previous studies have shown associations between SES in early life and later diseases such as cardiovascular disease The Newcastle Thousand Families study allows a large collection of prospective data to be analysed, and provides a unique opportunity to compare early and later life influences of kidney function at age 63–64 years. While the sample size of 354 participants was relatively small when compared to previous studies examining birth weight When examining the representativeness of the study in comparison to the original cohort, it was found that sex and SES at birth were both significantly different when compared to the proportions of the original cohort. No interactions were found for sex and variables significantly associated with eGFR, which confirms that there was no selection bias due to the change in representativeness of sex. Also, males and females were examined separately as well as combined. SES at birth was not found to be significantly associated with eGFR at age 63–64 years, but this cannot be representative of the original cohort, due to the significant change in the proportion of participants who returned from each category. Loss of oestrogen due to the menopause is potentially of a greater contribution to kidney function in females than the variables tested in this study. However, oestrogen levels were not assessed in this study, so further research into this hypothesis would be needed.A further weakness when examining size at birth in comparison to eGFR is that data were only recorded for birth weight, rather than other indicators for size at birth, such as birth length, ponderal index and fetal weight-to-placental weight ratio index. However, standardised birth weight was used, which is a better measure of fetal growth than crude birth weight, but no association with eGFR was seen.While for many years, eGFR has been used in assessing renal function, it has been shown to not be consistently associated with measured GFR across the normal range Birth weight and sex were the only early life factors found to be significantly associated with eGFR. However, no significant association was found for standardised birth weight. The contribution to eGFR from each of the significant variables was relatively small. The largest contribution to eGFR was from BMI, with nearly twice the variation explained than due to birth weight. As only a small amount of the variance in eGFR was accounted for by the variables investigated in this study, further studies comparing early and later life factors would be beneficial to determine different factors which may influence kidney function and which are the most important for focussing intervention studies.


P < 0.05). At birth, there was an interaction (P = 0.06) between treatment and sex for birth weight of the lamb. The ewe lambs from Arg-supplemented ewes were 12% (P < 0.05) heavier at birth compared with controls whereas birth weight of male lambs did not differ. These results indicate that maternal Arg supplementation enhanced brown fat stores in the fetus and countered some effect of fetal growth restriction due to litter size in female lambs. Increasing birth weight of female lambs and enhancing brown fat stores of all lambs may have important implications for lamb survival and postnatal growth.The objective of this study was to evaluate the effects of parenteral administration of L-arginine (Arg) to well-fed twin-bearing ewes from day (d) 100 of pregnancy to birth on fetal growth, body composition and neonatal behavior. Ewes received an i.v. bolus of either 345 μmol Arg-HCl/kg bodyweight or saline solution (control) 3 times a day. At d 140 of pregnancy, Arg-supplemented and control ewes were euthanized and fetal weight and fetal organ weight recorded, and maternal and fetal plasma concentrations of amino acids, hormones and metabolites analyzed. A subset of ewes was allowed to lamb and birth weight, body dimensions and behavior of the lambs in the first 2 hours(h) following birth recorded and blood samples collected. At d 140 of pregnancy, fetal weight internal organ weights were unaffected by treatment with the exception of brown fat stores which were increased by 16% in fetuses from Arg-supplemented ewes relative to controls ( The live weight of the ewes at mating was 65–75 kg with a body condition score of 3–3.5 ; Ewes were randomly assigned to Arg and control  groups at P95. At P97, polyvinyl catheters were inserted into the tarsal vein of the hind leg under brief anesthesia induced by injectable anaesthetic and sedation (combination of 0.5 mg/kg body weight (BW) Pamlin and 10 mg/kg body weight Ketamine, Parnell Technologies, Auckland, NZ). The externalized catheter was flushed with heparinized saline , sealed with stopcocks, secured in a plastic bag and anchored to the mid-line of the ewe. The bag and catheter were further secured with tube net. After catheter insertion, the ewes received prophylactic i.m. antibiotics .n = 23) or P100 to birth  ewes received either a bolus of Arg-mono-hydrochloride  or approximately the same volume of sterile saline, three times daily . The chosen Arg dose rate was based on the previous study by Lassala et al.  with a final concentration of 1.8 g Arg per 5 mL and pH adjusted to 7.0 with 1 mol/L NaOH. Each individual bolus was passed through a 0.22 μm PES syringe filter  directly into the catheter to ensure the solution was free of microbial pathogens. Between boluses, the catheters were flushed with heparinized saline (10 U/mL sodium heparin) to maintain patency and prevent clotting. For cohort 2, administration of treatment was ceased at the first signs of labor which was between 1 and 10 h prior to birth.At P120, ewes of both cohorts were blood sampled prior to (-5 minutes (min)) and 30, 60 and 180 min after Arg administration, using jugular venipuncture to determine the change in plasma amino acid concentrations over time. Plasma was separated and stored at -20°C until analyzed for amino acids, metabolites and hormones.n = 9; control n = 11).At P140, ewes of cohort 1 were blood sampled one h following Arg administration, just prior to euthanasia. After euthanasia of the ewes with 0.5 mL/kg BW Pentobarb 300  the abdominal cavity was opened to remove the gravid uterus, and opened to expose the fetuses. A blood sample from each fetus (cardiac puncture) was collected, followed by clamping of the umbilical cord and removal of the fetuses from the uterus. Weight of each fetus, sex, crown-rump-length and thoracic-girth circumference, lengths of front and hind legs and weights of the internal organs were recorded. Fetal brown fat weight was defined as the weight of all peri-renal adipose tissue  were allowed to lamb naturally. One ewe (control) from the original cohort of 26 was omitted from the study due to aborting her lambs for unknown reasons. Ewes were continuously monitored during the lambing period to identify any potential lambing difficulties and to observe and record lamb behaviours within the first 2 h after birth. The following lamb behaviours were recorded: time (recorded in min) taken to kneel, shake their head, try to stand, successfully stand, reach the udder, first unsuccessful suckle, first successful suckle, and the percentage of lambs that fed unassisted within 2 h of birth as previously reported by , P140 (n = 6/group) and 2 h post-birth (n = 5/group) were selected for analysis. Similarly, plasma samples from randomly selected P140 fetuses  and lambs at 2 h post-birth  were selected for analysis. Amino acids were determined by ion-exchange chromatography as previously described . The data were analysed using the NLME package in R (R Core Team P = 0.93 for Arg and control ewes), or cohort . Arginine did not affect ewe live weight in cohort 1 or cohort 2 throughout pregnancy  to have greater body condition scores on P120 and this difference was significant at P134 (P = 0.007) and P140 (P = 0.05) relative to control ewes  to have greater body condition scores on P113 relative to control ewes .Maternal Arg supplementation had no effect on fetal weight or body dimensions at P140 apart from front-leg length which tended to be longer for fetuses of Arg ewes compared to controls Table . ArgininP = 0.06) between Arg and lamb sex for birth weight, such that ewe lambs from Arg ewes were 12% heavier (P < 0.05) at birth compared to control female lambs . However, there was no difference in birth weight between male and female lambs born to Arg ewes . Rectal temperatures of lambs born to Arg ewes were higher than that of lambs born to control ewes , two h post-birth. Maternal Arg supplementation had little effect on crown-rump length of the offspring (data not shown). However, a treatment by sex interaction was observed for thoracic-girth circumference, such that female lambs born to Arg ewes tended to have a greater thoracic girth compared to female lambs born to control ewes . No effects of treatment on crown-rump-length or thoracic girth circumference were observed between male offspring, nor were there any effects of treatment on front or hind leg length (data not shown).At birth, there was a tendency for an interaction  to have greater concentrations of insulin relative to controls. No differences in concentrations of IGF-1, glucose, NEFA, glycerol and triglycerides were found between fetuses from Arg ewes compared to controls . A numerical difference was found for the percentage of lambs that were able to feed unassisted within 2 h of birth, such 80% of lambs born to Arg ewes were able to feed on their own vs. 57% of lambs born to control ewes (P = 0.12). A treatment by sex interaction (P = 0.02) was observed for the time taken to stand, such that male lambs born to Arg ewes took longer to stand than their control male counterparts . No such treatment effect was observed between females .A range of lamb behaviors were recorded at birth to provide estimates of lamb viability which, under farming conditions (i.e. when not continuously monitored and provided assistance when required) may influence lamb survival. Lambs born to Arg ewes tended to take longer to get to their knees  and polyamines which play a key role in placental angiogenesis and growth in mammals  or was increased (cohort 1). These observations contrast previous studies where Arg supplementation of multiple-bearing ewes had no effect on NEFA profiles (Lassala et al. To survive, newborn lambs need to quickly get access to colostrum to maintain body temperature. Colostrum intake is influenced by lamb vigor, maternal colostrum production and bonding between the mother and offspring (Nowak and Poindron In conclusion, Arg supplementation of twin-bearing ewes from P100 to birth improved brown fat stores in the fetuses at P140, birth weight of female lambs, and neonatal behaviors that may enhance survival. The potential for Arg to enhance the survival of multiple-born lambs has important implications for sheep production. Furthermore, using sheep as a model for humans, the findings in this study may contribute to the development of therapeutic interventions for women carrying twins.


Worldwide 15.5% of neonates are born with low birth weight, 95.6% of them in the developing countries. Prematurity accounts for 10% of neonatal mortality globally. The purpose of this study was to evaluate the effects of birth weight and gender on neonatal outcome.The data of 278 neonates managed in the Special Care Baby Unit (SCBU) of Jos University Teaching Hospital (JUTH) over a 2 year period from July 2006 to June 2008 were analyzed.One hundred and fifty nine (57.2%) were males and 119(42.8%) females. There were 87(31.3%) preterm and 191 (68.7%) term babies. Twelve of the babies died. Seven (2.52%) and 5 (1.80%) being males and females respectively. The neonatal mortality rate by gender was not significant (p > 0.05). The neonatal mortality was 25.2 deaths per 1000 live births for boys and 18.0 for girls. The mean birth weights of the preterm and term babies were 1.88 ± 0.47 kg and 3.02 ± 0.50 kg respectively, with a mean gestational age of 30.62 ± 3.65 weeks and 38.29 ± 0.99 weeks respectively.Eighty seven (31.3%) of the babies were of low birth weight, 188(67.6%) were of normal birth weight and 3(1.1%) high birth weight. Of the low birth weight babies, 6(2.2%) were term small for gestational age. Six (2.2%) of the preterm infants had normal birth weight.Eleven of the babies that died were preterm low birth weight. The overall mortality rate was 4.32%. The birth weight specific mortality rate was 126 per 1000 for the preterm low birth weight and 5 per 1000 for the term babies. Birth weight unlike gender is a significant predictor of mortality, mortality being higher in neonates of <2.5 kg  (p = 0.453). Seven (58.3%) and 4(33.3%) of the pre-terms that died were appropriate and large for gestational age respectively. Gestational age is not a significant predictor of neonatal mortality (p = 0.595). Babies delivered at less than 37 weeks of gestation recorded a higher rate of mortality than those of 37 weeks and above (p = 0.000).The subjects showed one or more major clinical indications for admission. The major clinical indications for the preterm and term babies were respectively as follows: neonatal sepsis 63(22.7%) and 124(44.6%); neonatal jaundice 32(11.1%) and 71(24.7%); malaria 9(3.1%) and 13(4.5%); birth asphyxia 3(1.0%) and 7(2.4%). Neonatal sepsis was a common denominator among the babies that died.Birth weight unlike gender is a significant predictor of neonatal outcome Worldwide, 15.5% of all infants are born with low birth weight, 95.6% of them in the developing countries ,3. PremaGender -specific infant mortality varies across nations . Male neIt is hypothesised that birth weight and gender have significant positive effects on neonatal mortality (p < 0.05).This is a retrospective descriptive study. The data of 278 neonates who were managed at the Special Care Baby Unit of Jos University Teaching Hospital, Jos, North- central Nigeria from 1st July 2006 to 30th June 2008 whose specimens were sent to the unit's research laboratory for various routine investigations were analyzed.Jos is the capital city of Plateau state located between latitude 80°24 'N and longitude 80°32' and 100°38'East [Consent was sought and obtained from the head of the records department of the hospital before extracting data from the patients' hospital records. Ethical clearance or consent of the neonates' parents/care giver was not obtained because the study was undertaken retrospectively. Information extracted from the neonates' records include: sex, gestational age at delivery, birth weight, morbidity, outcome and duration of illness before mortality.Data were analyzed using Epi-info version 3.3.2 . The meaOut of 278 neonates studied, 159 (57.2%) were males and 119(42.8%) females. Eighty- seven (31.3%) were preterm and 191(68.7%) term babies  this being higher in babies with birth weight of <2.5 kg (Table Two (0.7%) of the pre-terms were delivered at 17-20 weeks of gestational age category and were large for gestational age (LGA). Two (0.7%), 38 (13.7%) and 47 (16.9%) of the pre-terms were small for gestational age (SGA), appropriate for gestational age (AGA) and LGA respectively. 7(58.3%) and 4(33.3%) of the pre-terms that died were AGA and LGA respectively  [More boys than girls in our study died, though this was not significant. This is in consonance with the finding by some authors that male neonates have higher mortality rate than their female counterparts -7. This c.gc.ca) .Also from the study, though gestational age is not a good predictor of neonatal mortality, the latter tends to occur more at gestational age less than 37 weeks. This agrees with the finding by Herman and Hastie, 1990 . This imNeonatal infection may be a predisposing factor in the mortality of these low birth weight preterm neonates as most of the babies and particularly those that died were clinically diagnosed of neonatal sepsis. This is in agreement with works done in Ebonyi State  and LagoFinally, if the Millennium Development Goals (MDGs) which is a set of UN priorities slated to be met by 2015, with the fourth goal being on the reduction of the incidence of low birth weight deliveries for reducing child mortality by two thirds  is to beBirth weight unlike gender is a significant predictor of neonatal outcome.This implies that measures to reduce the rate of preterm low birth weight deliveries and improve on the survival of the preterm low birth weight neonates including intensive asepsis measures should be encouraged and given greater priority.Though, some infection control measures like separating inborn and out born, proper dressing of personnel, hand washing practices are in place in the unit there is still a high prevalent rate of sepsis among the babies admitted in the unit, thus it is being recommended that more stringent asepsis measures be put in place in order to reduce the rate of infections and the consequent mortality.Secondly, we recommend improvement in obstetric care to reduce low birth weight/prematurity rate; and improved neonatal care of low birth weight babies to enhance their survival.One major limitation of the study was that the data were extracted from the hospital records of babies whose specimens were sent to the unit's research laboratory within the stated time frame for various routine investigations, not necessarily the total number of admissions to the unit. Thus, a further study in which the total number of admissions to the unit is made use of may be necessary.The authors declare that they have no competing interests.OC conceived the idea, participated in data extraction, design, analysis and interpretation of data and drafting of the manuscript; OS participated in the design, interpretation of data and reviewing of the manuscript; IO participated in the design, analysis and interpretation of data and drafting of the manuscript; OE participated in reviewing the paper while TB participated in the design of the work. All the authors went through the final copy of the work and gave their final approval.Table S1. Z-test of Gestational Age (GA) and Mortality, Table S2. Neonatal Mortality by Cause of Death.Click here for file


Longer intervals between consecutive births decrease the number of children a woman can have. This results in beneficial effects on population size and on the health status of mothers and children. Therefore, understanding the practice of birth interval and its determinants is helpful to design evidence based strategies for interventions. The objective of this study was to determine duration and determinants of birth interval among women of child bearing age in Lemo district, southern Ethiopia in March 2010.A community based cross sectional study design with stratified multistage sampling technique was employed. A sample of 844 women of child bearing age were selected by using simple random sampling technique after complete census was conducted in selected kebeles prior to data collection. Structured interviewer administered questionnaire was used for data collection. Actual birth interval was measured with the respondents' memory since majority of the women or their children in the area had no birth certificate.Majority (57%) of women were practicing short birth interval length with the median birth interval length of 33 months. Actual birth interval length is significantly shorter than preferred birth interval length. Birth interval showed significant variation by contraceptive use, residence, wealth index, breast feeding and occupation of husbands.low proportion of optimal birth spacing practices with short actual birth interval length and longer preferred birth interval lengths were evident among the study subjects. Hence interventions to enhance contraceptive utilization behaviors among women in Lemo district would be helpful to narrow the gap between optimal and actual birth spacing. Birth interval is the length of time between two successive live births . BeginniFertility is an important component of population dynamics which plays a major role in changing the size and structure of a given population . FactorsOptimal spacing until the next pregnancy is generally understood to refer to resting period between pregnancies that allows the mother time to recover from pregnancy, labor and lactation . Longer Women in developing countries have shorter birth intervals than they would prefer. The main reason for short birth intervals is that many women in developing countries do not use contraception after birth and therefore are likely to become pregnant once fecundity returns . Birth sA community based cross sectional study was conducted in March 2010 in Lemo district. The study area is found in southern Ethiopia. It is located 230km south of the capital (Addis Ababa). According to 2005 census, female population in Lemo Woreda was 215,265. A sample of 844 women of child bearing age who experienced at least two deliveries and at least the last delivery being within the last five years prior to the data collection were included in the study. The sample size was determined with single population proportion formula by considering 50% proportion of women 15 - 49 years who spaced consecutive births 3 to 5 years (to obtain maximum sample size) with 95% confidence interval and design effect of 2. The study subjects were selected by using simple random sampling technique after a census was conducted in selected kebeles (the lowest administrative unit). The kebeles were stratified as urban and rural kebeles. Probability to proportional size allocation technique was used in the determination of the number of kebeles and study units included in each stratum. Two urban and six rural kebeles were randomly selected by using lottery method out of 8 urban and 35 rural kebeles. Because of 33 respondents were either absent or refused to participate in the study the response rate of the study was 96%.In this study we measured birth history and interval using 8 items, socio-demographic 26 items and behavioral variables 19 items and the internal reliability  of the instrument was 0.73. The knowledge level of the respondents was assessed for the advantages of practicing optimal birth spacing and the disadvantages of practicing short birth intervals both for the mother and the child using 7 items. Those respondents who scored at least 60% of the knowledge questions correctly and the right optimum number of months or years between two successive births were considered as knowledgeable. Actual birth interval was measures with the respondents' memory since majority of the women or their children in the area had no birth certificate. Since actual birth interval was measured with the respondents' memory we studied women with history of at least two deliveries and at least one of the births within the last five years to minimize the recall bias. We only measured the interval between the last child and the preceding child. Birth interval among the respondents has been tri-chotomized based on recent recommendations into short birth interval (less than 36 months), optimum birth interval (36 to 60 months) and long birth interval (above 60 months) categories ,16.Data was collected by trained female data collectors using interviewer administered questionnaire adapted from different literatures . First descriptive statistics was used to present the frequencies, of variables and followed by bivariate and multivariate analysis in order to see statistical association between the outcome and explanatory variables. Variables which showed significant association in the bivariate analysis were entered into multivariate logistic regression. Ethical approval was obtained from the Ethical Committee of Jimma University. Informed consent was obtained from the participants.out 811 study population, 552 (68.1%) were rural and the rest 259 (31.9%) were urban residents. The majority of the respondents 499(61.20%) were in the age ranges of 25-34 years. The mean and median age of the respondents was 31 (SD = 10.6) and 28 years respectively  have ever heard about optimum birth interval between live births. Among those who had the awareness, two hundred forty (31.5%) reported the optimum birth interval between two successive births to be below 36 months and 454(59.6%) of them reported it to be between 36 and 60 months. The rest are in the category greater than 60 months. Sixty percent of the study participants were Knowledgeable about optimum birth spacing. The results showed that almost all, 806 (99.4%) of the respondents, reported the presence of health advantages of practicing optimal birth interval and 807 (99.5%) reported the presence of negative consequences of practicing short birth interval.More than half 467(57.6%) of the study subjects had short birth interval. Two hundred ninety (35.8%) respondents had optimum birth interval and the remaining had long birth interval figure . The medThe difference between the means of actual and preferred birth interval length is found to be statistically significant . This shows that the mean preferred birth interval length is significantly greater than the mean actual birth interval length.The desire to have more children before the conception of the last child was asked. Accordingly, 632 (77.9%) of the respondents had the desire to have the last child. Of those who wanted more children, 448 (70.9%) wanted to become pregnant then and 184 (29.1%) desired to postpone the pregnancy to sometime later. Among others, problems associated with contraceptive usage 140 (17.3%) and not using modern family planning methods 39 (4.8%) were the main reasons for failing to postpone the last pregnancy. Among 427 family planning users, 132 (30.9%) had become pregnant prior to the time they desired between the last two pregnancies. Forty eight (11.2%) of the users became pregnant while wanting to limit child bearing.Rural women were more likely to have short birth interval than urban women [OR = 2.7 ]. Compared to being employee, daily laborers and students had high chance of having short birth interval. Similarly as the duration of breast feeding increases, the probability of short birth interval also increases. Women who were not using contraceptives are [OR = 1.6] times more likely to give birth within short period of time than users. Women with highest wealth quartile were 51% more likely to have short birth interval than with the lowest wealth quartile  of the women in reproductive age group have been practicing short birth interval below the recommended duration of optimal birth spacing. Regarding the median length of months between two successive births, women on average are 3 months behind what has been recommended as the healthiest birth interval.Women who were rural resident, being student and daily worker in husbands' occupation, breast feeding for 7 to 12, 13 to 23 and 24 and above months, non use of modern contraceptives and highest wealth quartile were found to be significant predictors of short birth interval length. Women in the study area have been practicing on average 7 months shorter birth interval length than they would prefer otherwise and the preferred length of birth interval among the study subjects is significantly greater than actual birth interval length. Interventions to enhance contraceptive utilization behaviors among women in Lemo district would be helpful to narrow the gap between optimal and actual birth spacing.The authors declare that they have no competing interests.SY, MW and MA designed the study, analyzed the data and drafted the manuscript. EG was involved in the analysis of the data and critically reviewed the article.All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2393/11/38/prepubQuestionnaire. A questionnaire for assessing duration and determinants of birth interval among women of child bearing ageClick here for file


Both low birth weight, an indicator of intrauterine growth restriction, and low grade systemic inflammation depicted by high sensitivity C-reactive protein (hs-CRP) have emerged as independent predictors of cardiovascular (CV) disease and type 2 diabetes. However, information linking low birth weight and hs-CRP in a biracial (black/white) population is scant. We assessed a cohort of 776 black and white subjects  aged 24-43 years (mean 36.1 years) enrolled in the Bogalusa Heart Study with regard to birth weight and gestational age data were retrieved from Louisiana State Public Health Office.Black subjects had significantly lower birth weight than white subjects  and higher hs-CRP level . After adjusting for sex, age, body mass index (BMI), smoking status and race , the hs-CRP level decreased across quartiles of increasing birth weight in white subjects (p = 0.001) and the combined sample (p = 0.002). Adjusting for sex, age, BMI, smoking status and race for the total sample in a multivariate regression model, low birth weight was retained as an independent predictor variable for higher hs-CRP levels in white subjects (p = 0.004) and the total sample (p = 0.007). Conversely, the area under the receiver operative curve (c statistic) analysis adjusted for race, sex, age, smoking status and BMI yielded a value of 0.777 with regard to the discriminating value of hs-CRP for predicting low birth weight.The deleterious effect of low birth weight on systemic inflammation depicted by the hs-CRP levels in asymptomatic younger adults may potentially link fetal growth retardation, CV disease and diabetes, with important health implications. The growth of an undernourished fetus results in adaptive fetal programming or metabolic imprinting, with permanent changes in structure, metabolism and physiology of fetal organs and related pathophysiologic consequences in later life ,2. StudiInflammation plays an important role in the pathogenesis of atherosclerosis -9. Risk The study sample was derived from a cohort of 1203 subjects aged 23 to 43 examined as a part of a longitudinal follow-up survey. Of these, information on 908 singletons with hs-CRP measurement, birth weight, gestational age and body mass index (BMI) data were available. The exclusion of 132 singletons born premature (<37 weeks of gestation) and/or had conditions (with or without medication) of diabetes, hypertension and dyslipidemia left 776 eligible participants . Birth weight and gestational age data were retrieved from Louisiana State Public Health Office. Tulane University Medical Center Institutional Review Board approved the study, and informed consent was obtained from all participants.Standardized techniques and protocols were used by trained examiners. Height and weight were measured twice and the mean values were used to calculate BMI as a measure of adiposity. Information on smoking status was obtained by questionnaires. Those who had smoked at least one cigarette per week during the past one year or more were identified as current smokers, and the remainder as non-smokers. Plasma high sensitivity hs-CRP levels were measured by latex particle-enhanced immunoturbidemetric assay on a Hitachi 902 Automatic Analyzer . The reproducibility of hs-CRP measurement checked with 10% of randomly assigned pairs of blind duplicate analysis, which gave an intraclass correlation coefficient of 0.99.Statistical analyses were done with SAS software, version 9.1 . As the hs-CRP level was not normally distributed, log transformation was used to approach normality. Analyses were performed where appropriate on transformed data. Analysis of variance for race difference in mean values of continuous variables and chi-square test for categorical variables were used. Because of a strong association between gestational age and birth weight, the latter was adjusted by regression analysis models to the mean values of the former in each race-sex group. For categorical analysis, quartiles of gestational age-adjusted birth weight were defined by using cut-off points in race-sex groups. Covariates adjusted mean values of hs-CRP were calculated by general linear models and used for analysis of birth weight by quartiles. Multiple regression analysis was used to determine the independent association of birth weight with hs-CRP in relation to the measured covariates. Two steps were followed in the regression model: the logarithm of hs-CRP was used in both cases as a dependent variable to determine the association between birth weight and hs-CRP. Model 1 was adjusted for age, sex, smoking and race  and the model 2 was adjusted for the above variables along with the potential confounding variable, BMI. In addition, a multivariate c-statistic model was used to determine the ability of hs-CRP to predict low birth weight (defined as <2500 gm). The area under the receiver-operating characteristic curve (c-statistic) was evaluated after adjusting for the covariates race, sex, age, smoking status and BMI. C-statistic of >0.5 indicated increased predictive ability.Table Figure Table Figure This community-based study demonstrates an inverse and independent association between birth weight and hs-CRP, a widely used biomarker of systemic inflammation. In addition, female sex, BMI and smoking were independent adverse correlates of hs-CRP. It is noteworthy that these findings support the emerging concept of intrauterine imprinting and its pathophysiologic consequences later in life by linking low birth weight to excess hs-CRP ,2.Although previous study in children has failed to find significant association between birth weight and hs-CRP , our epiAlthough observational studies like this cannot address the issue of causality, several putative mechanisms might link low birth weight to underlying perturbation in inflammatory pathways in utero. Undernutrition in utero causes permanent impairment in growth, structure, and function of muscle ,20, fat As in previous studies ,32, obesIn conclusion, low birth weight for gestational age is characterized by increased hs-CRP levels. In conjunction with earlier studies, these findings support the view that low birth weight, albeit a crude surrogate indicator of adaptive fetal programming, is a potential early risk factor for the emergence of disorders related to the activation of inflammatory pathways. As stated by Barker , primaryhs-CRP: high sensitivity C-reactive protein; BMI: body mass index.The authors declare that they have no competing interests.ARB participated in study design, data analysis and manuscript preparation. SRB, WC and GSB contributed to study concept and design, data collection, acquisition of funding and manuscript preparation. MJA involved in manuscript preparation. All authors listed have made substantial contributions on this article


Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is the most common presentation of a disorder of sex development (DSD) in genetic females. A report of prenatal growth retardation in cases of 46,XY DSD, coupled with observations of below-optimal final height in both males and females with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, prompted us to investigate prenatal growth in the latter group. Additionally, because girls with congenital adrenal hyperplasia are exposed to increased levels of androgens in the absence of a male sex-chromosome complement, the presence or absence of typical sex differences in growth of newborns would support or refute a hormonal explanation for these differences.In total, 105 newborns with congenital adrenal hyperplasia were identified in our database. Gestational age (weeks), birth weight (kg), birth length (cm) and parental heights (cm) were obtained. Mid-parental height was considered in the analyses.P > 0.05). The expected sex difference in favor of heavier males was not seen (P > 0.05). Of the 105 subjects, 44  had birth length and gestational age recorded in their medical chart. Mean birth length for this subgroup was 50.90 cm (63rd percentile), which differed from the expected standard population median of 50th percentile (P = 0.0082). The expected sex difference in favor of longer males was also not seen (P > 0.05).Mean birth weight percentile for congenital adrenal hyperplasia was 49.26%, indicating no evidence of a difference in birth weight from the expected standard population median of 50th percentile (The prenatal growth retardation patterns reported in cases of 46,XY disorders of sex development do not generalize to people with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Sex differences in body weight and length typically seen in young infants were not seen in the subjects who participated in this study. We speculate that these differences were ameliorated in this study because of increased levels of prenatal androgens experienced by the females infants. For example, low birth weight is more common in newborns with isolated hypospadias -9 and innewborns .Low birth weight is of concern, independently of its relationship with atypical reproductive development, because of the association with development of metabolic, endocrine and cardiovascular diseases later in life . FurtherCongenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OH) is the commonest cause of DSD in 46,XX individuals. Females with this condition are exposed during early development to levels of androgens that can be similar to the atypically low levels of androgens experienced by some genetic males with DSD. Furthermore, both under- and over-treatment of CAH with glucocorticoids results in a final adult height that is shorter than that predicted from mean parental height (MPH) . A betteTo our knowledge, only three published studies have analyzed prenatal growth in newborns with CAH due to 21-hydroxylase (21-OH) deficiency. The first study reported normal birth weight , and theThe goal of the present study was to retrospectively evaluate birth weight and length in newborns with CAH due to 21-OH deficiency whereas controlling for the influence of parental height. Furthermore, because female newborns with CAH due to 21-OH deficiency are exposed to increased levels of androgens before treatment in the absence of a male sex-chromosome complement, their growth patterns allow us to discriminate between hormonal versus genetic influences in the context of sexually dimorphic anthropometric measures.The study was approved by the institutional review boards of the University of Oklahoma Health Sciences Center and the Johns Hopkins School of Medicine, informed consent was not required.A retrospective chart review was performed on all pediatric endocrine charts from both clinics collected over the past 50 years. Subjects with CAH due to 21-hydroxylase deficiency were identified from each institution and reviewed . Gestational age (weeks), birth weight (kg), birth length (cm) and parental heights (cm) were obtained when documented in the chart. Subjects of gestational age < 37 weeks or > 44 weeks were omitted from the analyses. A single instance of twin gestation was identified in our data, but was excluded from the current analyses based on delivery at 34 weeks gestational age.http://www.cdc.gov/epiinfo), yielding birth weight, length, and weight, for, height percentiles and z-scores. MPH was calculated based on the formula:  ± paternal height (cm) ± 13 cm  [Birth weight and length information were entered into a software program  .U-test and Student t-test were used to examine the difference in study variables between male and female subjects with CAH. Spearman correlation coefficients were also calculated to determine the strength of the relationship between MPH and both birth weight (kg) and birth length (cm).Wilcoxon signed-rank tests were used to test whether birth weight and length percentiles differed from the standard median (50th percentile), and the Mann-Whitney t (103) = -1.18, P > 0.05). Mean birth weight percentile for CAH was 49.26%, indicating no difference in birth weight from the expected standard population median of 50th percentile . There was no sex difference in birth weight percentile between male and females subjects .Of the 105 subjects, 91% were born between 37 and 40 weeks. Gestational age ranged from 37 to 43 weeks (mean ± SD 39.91 ± 1.04). Mean birth weight for CAH subjects was 3.42 kg, with an average female and male weight of 3.39 and 3.50 kg, respectively . The mean birth length percentile for all subjects was 63.11%, which differed from the expected standard population median of the 50th percentile . In total, 68 subjects had their MPH calculated, but only 30 subjects had four data points available  to analyze. There was no significant correlation between birth weight  or length  percentiles and MPH.Of the 105 subjects with CAH, 44  had birth length and gestational age recorded in their chart  system, adequate nutrient and oxygen supply to the fetus, and normal imprinting of genes involved in early growth. For example, children with IGF-1 deficiency have depressed patterns of prenatal growth despite their exposure to typical levels of androgens during gestation . Additioin utero, including 17-hydroxyprogesterone. Studies of non-human animal models indicate that maternal activation of the hypothalamic-pituitary-adrenal axis during pregnancy results in alterations in offspring body mass, but not skeletal growth [in utero have reduced body mass [For newborns with CAH due to 21-OH deficiency, increased birth length could be due to a relative deficiency of cortisol, which has well-known growth-suppressing effects, or to excess levels of adrenal hormone precursors l growth -39. Convody mass , limb leody mass ,42 and cIt seems that newborns with CAH have already experienced some alterations in linear growth compared with their unaffected counterparts. Possibly, some of the difficulty seen in effecting normal linear growth throughout childhood of individuals with this disorder may be independent of post-natal cortisol-replacement regimens.The prenatal growth retardation patterns reported in cases of 46,XY DSD do not generalize to individuals with CAH due to 21-OH deficiency. Sex differences in body weight and length typically seen in young infants were not observed in the subjects who participated in this study. We speculate that these differences were ameliorated in this study due to increased levels of prenatal androgens experienced by the female infants.The authors declare that they have no competing interests.The work presented here was carried out in collaboration between all the authors. All authors read and approved the final manuscript.


Pregnancy in adolescents is a worldwide health problem and has been mostly common in poor populations. It is not clear if socioeconomic or biological factors are the main determinants of perinatal adverse outcomes in pregnant adolescents. Adolescents under 15 years old may present a high growth rate which may contribute to impair fetal growth. Our aim is to compare perinatal characteristics among early (aged 10 to 14 years) and late (aged 15 to 19 years) pregnant adolescents.A cross-sectional study was performed using data from Pernambuco State 2009, obtained from DATASUS/SISNAC, a Brazilian Government, open-access public health database. Maternal and neonatal outcomes were compared between early (aged 10–14 years) and late (aged 15–19 years) pregnant adolescents. Family income was compared between early and late pregnant adolescents using a sample of 412 subjects evaluated at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) during 2011. Statistical comparisons were made using the chi-square test was used with a significant level of 0.05; bivariate and multivariate analysis were performed. This project was approved by the Institutional Ethics Review Board.Data from 31,209 pregnant adolescents were analyzed. 29,733 (95.2%) were aged 15 to 19 years and 1,476 (4.7%) were aged 10 to 14 years. There were significant differences with respect to marital status, education level and number of prenatal visits of mothers aged 10 to 14 years compared to 15 to 19 years. Of importance, early adolescents had a greater rate of neonates born premature and with low birth weight. Prematurity and low birth weight remained statistically significant after multivariate analysis.Early aged adolescents may have an increased risk of prematurity and low birth weight. These findings highlight the potential role of biological factors in newborn outcomes in pregnant adolescents. Adolescent pregnancy is a worldwide health problem especially relevant in developing countries,2. It isHowever, it is unclear whether biological or socio-economic factors are more important for the adverse outcomes in the pregnant adolescent. For some researchers, biological factors such as age or maternal growth are not a risk factor, and unfavorable outcomes are more likely associated with socio-economic and lifestyle factors-7. IndeeMost studies in the pregnant adolescent focus on adolescents aged 15 to 19 years whereas information about pregnancy at younger ages usually appears only in aggregate statistics-14. AdolIn Pernambuco State, 31,209 live births from teenage mothers were registered during 2009 were registered; 29,733 (95.2%) were aged from 15 and 19 years and 1,476 (4.7%) aged from 10 to 14 years.The maternal characteristics were different among early and late pregnant adolescents regarding marital status, education level and number of prenatal consultations Table. There wLower birth weight  and preterm birth  remained statistically significant after multivariate analysis, but not Apgar score .Early pregnant adolescents in Pernambuco, Brazil, in 2009, gave birth to neonates with lower birth weight and also had a higher rate of preterm births, as compared with late pregnant adolescents. In Brazil, teenage pregnancy is more common among lower income adolescents and in Pernambuco state over 90% of births are registered at public hospitals. ImportaThe influence of biological factors on pregnant adolescent outcomes has not been adequately studied in humans. Birth weight, for example, depends more on environmental than genetic factors. A limitOur findings are consistent with others studies. Conde-Agudelo et al. found thHowever there are some discordant findings. Magalhães et al. found diOur study has some limitations. First of all we studied a secondary data provided by the Brazilian Government through DATASUS/SINASC. However, these data have been widely used and the health information system in Brazil has been more rigorous and precise in their collecting and dissemination. Secondly, we could not control for other variables that contributes to low birth weight, preterm birth and neonatal vitality. Nevertheless, smoking and alcohol consumption in adolescents increase with age at adolescence, and primiparity is associated with lower birth weight but not with preterm birth. It should be added that we have studied a large number of adolescents and we found a strong difference among neonatal outcomes.Our findings suggest that early adolescent pregnancy may increase the risk of low birth weight and preterm birth. Biological maternal characteristics of an early pregnant adolescent may be more important than socio-economic factors for adverse outcomes in adolescent pregnancy.http://www.datasus.gov.br), a national open-access public health system database, organized and maintained by the Brazilian government. 141,815 records of live births were observed and 31,209 (22.0%) teen mothers (aged 10 to 19 years) were studied in Pernambuco State during 2009.This cross-sectional study analyzed data from DATASUS/SINASC database  seen from March to December, 2011, at Instituto de Medicina Integral Prof Fernando Figueira (IMIP), Recife, Pernambuco.The number of inhabitants from Pernambuco State was obtained from the IBGE - The Brazilian Institute of Geography and Statistics (15).Ethics approval was obtained from the Ethics Review Boards at IMIP. A descriptive analysis of the data was performed through frequency tables with numbers and percentages. Socio-economic and biological characteristics among early and late pregnant adolescents were compared. Chi-square test was used with a significance level of 0.05. Bivariate and multivariate analysis were performed using the Statistical Package Social Science (SPSS) Version 15 was used.The authors declare they have no competing interests.Each author has participated sufficiently and actively in this study. JGA conceived and coordinated the study, drafted the manuscript; RMC contributed to the data collection and made a substantial contribution to analysis and interpretation; LPD also contributed to the data collection and the editing of the manuscript; RAP has participated in the design of the study and performed the statistical analysis. Each author revised the manuscript and provided the final approval of the version to be published.


Premature birth is the world’s leading cause of neonatal mortality with worldwide estimates indicating 11.1% of all live births were preterm in 2010. Preterm birth rates are increasing in most countries with continual differences in survival rates amongst rich and poor countries. Preterm birth is currently an important unresolved global issue with research efforts focusing on uterine quiescence and activation, the ‘omics’ approaches and implementation science in order to reduce the incidence and increase survival rates of preterm babies. The journal Reproductive Health has published a supplement entitled Born Too Soon which addresses factors in the preconception and pregnancy period which may increase the risk of preterm birth and also outlines potential interventions which may reduce preterm birth rates and improve survival of preterm babies by as much as 84% annually. This is critical in order to achieve the Millennium Development Goal (MDG 4) for child survival by 2015 and beyond. Whilst this ranking has decreased 4 places since 1990 there is a large continued disparity when compared directly with developed countries, where these complications make up the 35th greatest cause, a decline from the 21st in 1990 [Preterm birth is an unresolved global health issue. Globally it is the largest contributor to neonatal mortality and the second largest contributor to all under-5 mortality . Preterm in 1990 .Paradoxically, some rich countries have higher rates of preterm birth than some very poor countries. There are many possible explanations for this anomaly. In rich countries there are several factors that can lead to preterm birth, such as advanced maternal age, In Vitro Fertilization techniques resulting in multiple pregnancies, high rates of caesarean sections, and the management of complicated pregnancies that may result in induction of a preterm birth. Unlike the majority of indicators during the reproductive period, preterm birth is a measure of age at birth rather than a disease, complication, or death. This measure of age requires good dating of the last menstrual period, which is a major constraint particularly for the poorest women in low-income countries who often receive late or no antenatal care. In some cultures, poor dating is related to poor observance of the calendar-year or the use of other calendars. Additionally for these women, use of early ultrasounds to better date their pregnancy is almost non-existent.We are thus faced with this important and unresolved problem. For many years, intense research efforts have been focused on solving this problem, but still there is no solution. Preterm birth represents a common end point to a wide variety of clinical conditions, including spontaneous preterm birth with intact membranes or as a result of premature rupture of membranes, iatrogenic/medically induced preterm birth, multiple pregnancy preterm birth, foetal malformation/stillbirth, cervical incompetence, chorioamnionitis and self-induced preterm birth . In someAnother challenge is the fact that the few evidence-based interventions which could reduce the burden of preterm birth are often not used, especially in resource-limited settings. A relevant area of research relates to testing interventions that aim to increase the use of intervention of proven effectiveness: implementation science. Antenatal corticosteroids and Kangaroo Mother Care are attractive interventions that need to be tested in middle and low income countries in order to assess the best methods to implement them, and to measure the benefit in the survival of and future outcomes for preterm babies ,10.The journal Reproductive Health is very pleased to publish the supplement Born too Soon which underlines that preterm birth is an unfinished agenda for action and research . This suThis message is relevant to many stakeholders including scientists, clinicians, governments, and donors; a joint effort from all of whom could bring about these envisaged changes.JMB is the editor-in-chief, JH and PB are members of the Editorial Board and NS is the Journal Development Editor of Reproductive Health Journal.