However, the problem also remains substantial in high-income countries in Europe, North America, and Australia and New Zealand, where there has been virtually no progress in reducing low birthweight rates since 2000, according to a new analysis undertaken by researchers from the London School of Hygiene & Tropical Medicine, UNICEF, and the World Health Organization (WHO), involving 148 countries and 281 million births, published in The Lancet Global Health journal.

In 2012, all 195 member states of the WHO committed to a 30% reduction in low birthweight prevalence by 2025, compared with 2012 rates. The estimates, which are the first of their kind, found that worldwide low birthweight prevalence fell slightly from 17.5% in 2000 (22.9 million low birthweight livebirths) to 14.6% in 2015 (20.5 million).

However, the study indicates that at the current rate of progress — with a 1.2% yearly decline in low birthweight rates between 2000 and 2015 — the world will fall well short of the annual reduction rate of 2.7% required to meet the WHO target of a 30% reduction in prevalence between 2012 and 2025.

These findings highlight the urgent need for more investment and action to accelerate progress, through understanding and tackling key drivers of low birthweight throughout life — including extremes of maternal age, multiple pregnancy, obstetric complications, chronic maternal conditions (eg, hypertensive disorders of pregnancy), infections (eg, malaria), and nutritional status, as well as exposure to environmental factors such as indoor air pollution, and tobacco and drug use. In low-income countries, poor growth in the womb is a major cause of low birthweight. In more developed regions, low birthweight is often associated with prematurity (a baby born earlier than 37 weeks gestation).

“Despite clear commitments, our estimates indicate that national governments are doing too little to reduce low birthweight. We have seen very little change over 15 years, even in high-income settings where low birthweight is often due to prematurity as a result of high maternal age, smoking, caesarean sections not medically indicated and fertility treatments that increase the risk of multiple births. These are the underlying issues that governments in high-income countries should be tackling,” says lead author Dr Hannah Blencowe from the London School of Hygiene & Tropical Medicine, UK. “To meet the global nutrition target of a 30% reduction in low birthweight by 2025 will require more than doubling the pace of progress.”

The study authors call for international action to ensure that all babies are weighed at birth, to improve clinical care, and to promote public health action on the causes of low birthweight to reduce death and disability.

“Every newborn must be weighed, yet worldwide, we don’t have a record for the birthweight of nearly one third of all newborns,” says co-author Julia Krasevec, Statistics & Monitoring Specialist from UNICEF. “We cannot help babies born with low birthweight without improving the coverage and accuracy of the data we collect. With better weighing devices and stronger data systems, we can capture the true birthweight of every baby, including those born at home, and provide better quality of care to these newborns and their mothers.”

More than 80% of the world’s 2.5 million newborns who die every year are low birthweight because they are either born preterm and/or small for gestational age. Low birthweight babies who survive have a greater risk of stunting, and developmental and physical ill health later in life, including chronic conditions such as diabetes and cardiovascular disease.

In this study, the researchers performed a comprehensive search of the available data from national government databases and national surveys to estimate prevalence and track trends on low birthweight for livebirths in 148 countries from 2000 to 2015. In total, data were collated from over 281 million births. However, the authors note that 47 countries (including 40 low- and middle-income countries that account for almost quarter of all births worldwide) had insufficient data available.

One of the lowest rates of low birthweight in 2015 was estimated in Sweden (2.4%). This compares to around 7% in some high-income countries including the USA (8%), the UK (7%), Australia (6.5%), and New Zealand (5.7%).

The regions making the fastest progress are those with the highest numbers of low birthweight babies, Southern Asia and Sub-Saharan Africa, with a yearly decline in low birthweight prevalence of 1.4% and 1.1%, respectively, between 2000 and 2015.

Nevertheless, the overall number of low birthweight livebirths has actually increased in sub-Saharan Africa from 4.4 million to 5 million babies, largely due to demographic trends (such as fertility and migration). Similarly, Southern Asia still has almost half of the world’s low birthweight livebirths, with an estimated 9.8 million in 2015.

High-income countries in North America, Europe, and Australia and New Zealand are some of the slowest progressing countries with an average reduction in prevalence of 0.01% per year and a consistent rate of low birthweight of 7% per year between 2000 and 2015.

Within these regions, Czechia (yearly increase 2%), Ireland (1.3%), Portugal (1.2%), and Spain (1.1%) are making the slowest progress, with an upward trend in low birthweight prevalence since 2000. Overall, the UK has experienced a downward trend in prevalence (yearly decline 0.3%) since 2000, with total numbers fluctuating due to changes in livebirths each year (50,741 low birthweight livebirths in 2000 to 56,001 in 2015).

“Low birthweight is a complex clinical entity composed of intrauterine growth restriction and preterm birth,” says co-author Dr Mercedes de Onis from WHO, Switzerland. “This is why reducing low birthweight requires understanding of the underlying causes in a given country. For example, in Southern Asia a large proportion of low birthweight babies are born at term but with intrauterine growth restriction, which is associated with maternal undernutrition including maternal stunting. Conversely, preterm birth is the major contributor to low birthweight in settings with many adolescent pregnancies, high prevalence of infection, or where pregnancy is associated with high levels of fertility treatment and caesarean sections (like in USA and Brazil). Understanding and tackling these underlying causes in high-burden countries should be a priority.”

The researchers note that whilst the study provides the only systematic data on low birthweight in all countries, it relies on modelling estimates that may be affected by a lack of data in low- and middle-income countries. Nearly half (48%) of all data points came from high-income countries compared to just 13% from sub-Saharan Africa and Asia, the regions with the highest prevalence rates and that accounted for three-quarters of all low birthweight babies born in 2015.

The authors note several other limitations, including that the estimated trends are driven by changes in associated factors such as neonatal mortality and childhood undernutrition, which might not accurately reflect true changes in prevalence. Therefore, the gap to achieve the WHO target could be even wider. Whilst the authors adjusted survey data for heaping and missing data, they note that the low birthweight data available from low- and middle-income countries are predominantly from household surveys that are susceptible to bias owing to missing and misreported birthweights — which could underestimate low birthweight prevalence.

Commenting on the implications of the findings, Professor Tanya Doherty from the South African Medical Research Council, South Africa, says: “The authors present an urgent and practical call to action to greatly improve the coverage of weighing at birth, including the need to count and weigh all babies (livebirths and stillbirths), strengthen existing data and health systems, and innovate better weighing devices. Yet achieving this practically, especially in emergency settings or weak health systems, remains a challenge.”

Nevertheless, she adds: “These new low birthweight estimates provide an opportunity to advance the agenda and call upon all stakeholders to take concerted action in the effort to ensure that every newborn is weighed at birth, and that the information is collated and used for local action and accountability at the household, community, district, national and global levels. At the same time, we must improve care for the 20.5 million low birthweight infants and their families each year.”

Overhunting, as opposed to deforestation, is undetectable by remote-sensing techniques, and to date, there were vast understudied areas in the tropics where hunting impacts on mammal communities were unknown. In this study, the authors have projected for the first time the spatial patterns of hunting-induced mammal defaunation in the tropics and have identified areas where hunting impacts on mammal communities are expected to be high.

Predicted hotspots of hunting-induced defaunation are located in West and Central Africa, particularly Cameroon, and in Central America, NW South America and areas in SE Asia (Thailand, Malaysia and SW China). Predictions were based on a newly developed hunting regression model, based upon socio-economic drivers, such as human population density and hunters’ access points, and species traits, such as body size. The model relies on more than 3,200 abundance data estimates from the last 40 years and included more than 160 studies and hundreds of authors studying approximately 300 mammal species across the tropics.

These defaunation maps are expected to become an important input for large-scale biodiversity assessments, which have routinely ignored hunting impacts due to data paucity, and may inform species extinction risk assessments, conservation planning and progress evaluations to achieve global biodiversity targets.

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The findings, published online today in the New England Journal of Medicine, could lead to more precise matching between donors and patients, and reduce kidney transplant failures. The same genomic collision may also potentially occur in heart, liver, and lung transplants.

A Different Possible Mechanism for Kidney Rejection

A successful organ transplant depends in large part on assuring genetic compatibility between donor and recipient. This is done by matching the donor and recipient’s human leukocyte antigens (HLAs) — cell surface proteins that help the immune system determine which cells are foreign — as closely as possible. But HLA mismatches can only explain only about two-thirds of transplants that fail for immunological reasons. “The rest of those failures are probably due to less common antigens, or so-called minor histocompatibility antigens. However, the identity of most of these antigens and how they lead to rejection is largely not known,” says co-senior author Krzysztof Kiryluk, MD, the Herbert Irving Assistant Professor of Medicine at Columbia University Vagelos College of Physicians of Surgeons.

The researchers hypothesized that a person whose genome carries a kidney gene with a deleted section might be especially sensitive to organs from a donor whose genome carries the full-sized gene. “The recipient would then be exposed to a protein their immune system would sense as foreign,” says Kiryluk.

To test their hypothesis, they screened 705 kidney recipients transplanted at Columbia University Irving Medical Center for deletions in 50 kidney genes that were present as full-sized versions in the donor. The deletions associated with rejection were then confirmed in an additional 2,004 donor-recipient pairs from three international transplant cohorts.

What the Study Found

The study found that kidney recipients with two copies of a deletion near a gene called LIMS1 had a significantly higher risk of rejection when the donor kidney had at least one full-sized version of the same gene. The risk of rejection was 63 percent higher among the donor-recipient pairs with this genomic collision, compared to those without this mismatch. “To put this into perspective, the risk of rejection from LIMS1 mismatch is roughly three times as high as the risk due to a single allele mismatch in the HLA,” Dr. Kiryluk says.

Kidney transplant recipients with two copies of the deletion who developed rejection had detectable levels of anti-LIMS1 antibodies in their blood — further evidence that this genomic collision contributes to rejection.

“The exact mechanism by which this deletion exerts its effects is unknown,” says Kiryluk. “It’s likely that it reduces the amount of LIMS1 protein produced, since we find that individuals with two copies of the deletion have lower levels of LIMS1 gene transcript in their kidneys. When these individuals are exposed to a high level of LIMS1 protein in a newly transplanted organ, their immune system is more likely to recognize the LIMS1 antigen as foreign, resulting in rejection.”

Transplanted organs commonly experience a significant period of low oxygenation, which appears to compound the genomic collision. In cells that produce LIMS1, the researchers found that low oxygen levels increase LIMS1 production on the cell surface, which may increase the risk of an immune attack.

1 in 7 Transplants in Some Populations May Be Affected

LIMS1 mismatches would be expected to occur in approximately 12 to 15 percent of transplants from unrelated donors among persons of European and African ancestry, but it would be very rare among persons of East Asian ancestry because the deletion is very rare in these populations.

“LIMS1 mismatches could be avoided by pre-transplant genetic screening,” Kiryluk says. “But first we need to validate our findings in larger studies.”

The findings may apply to other types of organ transplants since LIMS1 is also expressed in the lung, heart, and liver. Similarly, other genetic incompatibilities may also be contributing to rejection of these organs.

“This project illustrates how genetic analysis is empowering clinical care by enabling better matching and the antibody test potentially presents a noninvasive method for screening for organ rejection in individuals with an existing transplant,” says co-senior author Ali G. Gharavi, MD, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons.

The LIMS1 gene has gone previously undetected in earlier searches, partly due to the limited sample size of previous studies, Kiryluk says. “We estimate that a traditional genome-wide association study would need to analyze a minimum of 13,000 kidney recipients to find this gene,” he adds. “The genomic collision approach provides a new method to find additional mismatches in a smaller number of donor-recipient pairs. And coupled with new methods of antibody detection, is likely to propel future discoveries in this area.”