Maternal mortality is a critical problem in public health that affects women worldwide, and the rate has increased post-COVID. In the US alone, the maternal mortality rate for 2021 was 32.9 deaths per 100 000 live births, up from 23.8 in 2020 and 20.1 in 2019. This mortality refers to a woman dying from any reason connected to or aggravated by the pregnancy or within 42 days of the termination of the pregnancy. According to estimates from the World Health Organization (WHO), over 295,000 women die worldwide each year from problems related to pregnancy and delivery, and unfortunately,  94% of these deaths take place in low- and middle-income nations. This indicates that a woman passes away from pregnancy or childbirth-related problems every two minutes. Although the vast majority of these fatalities take place in underdeveloped nations, maternal mortality is still a serious problem in industrialized nations. Progress is being made to reduce maternal mortality rates globally, but there are still many challenges that women face during pregnancy and childbirth, both in developed and developing countries.

The higher number of maternal deaths during the past recent years, is due to the fact that the COVID pandemic disrupted health services, reducing access to maternal healthcare, and limiting mobility due to lockdowns and travel restrictions. Reduced staffing and resources for maternal healthcare due to hospitals being overwhelmed with COVID-19 patients has further compounded the issue. On top of this, the additional fear of pregnant women contracting COVID-19 in healthcare settings has led to delayed diagnosis and treatment of pregnancy and childbirth complications.

Many women even in developed nations still lack access to high-quality care during pregnancy and childbirth. This is due to the fact that there aren’t enough healthcare providers, particularly in rural locations, or to lack of proper transportation to the healthcare facilities nearby. Sadly, there are racial and ethnic differences in healthcare access and outcomes, with non-caucasian women in the US and UK experiencing disproportionately high rates of maternal mortality.

Another challenge is the increasing number of cesarean sections (C-sections) being performed. Although C-sections can be a life-saving procedure, they are overused in many developed countries. Childbirth is often seen as a medical event, rather than a natural process, which contributes to the overuse of C-sections. C-sections can lead to more complications for both the mother and the baby, an increase in healthcare costs, and ultimately increases the maternal mortality rate.

In contrast, when it comes to maternal mortality, underdeveloped nations have unique difficulties. The main issue is that not everyone has access to high-quality healthcare. Women give birth at home frequently in impoverished nations without the aid of trained delivery attendants, such as midwives, which can result in potentially fatal complications. These underdeveloped nations’ healthcare systems frequently lack the tools, and materials, and have a shortage of qualified staff members who can offer adequate care for pregnant women.

Furthermore, pregnant women in developing nations face serious difficulties such as poverty, starvation, and illiteracy, which can also negatively affect maternal health and raise the risk of maternal death. Individuals who are underprivileged or undernourished might not have access to sufficient medical treatment or healthy nourishment during pregnancy, which can cause complications during childbirth.

Many efforts can be made to lower maternal mortality rates on a worldwide scale. First and foremost, there needs to be a focus on expanding access to high-quality healthcare for all women, irrespective of their socio-economic situation or place of residence. This can be accomplished by making investments in the infrastructure of the healthcare system, training more healthcare professionals, and expanding access to family planning and contraception services. Second, women should be more aware of the potential negative effects of medical procedures performed during childbirth, such as C-sections. Finally, increasing maternal health outcomes depends on tackling social determinants of health such as poverty, hunger, and illiteracy.

Maternal mortality is a complex issue that affects women in both industrialized and developing nations. There are still numerous issues that need to be resolved to reduce maternal mortality, but we should work toward lowering maternal mortality rates by making sure that all women have access to safe and healthy pregnancies and by improving access to high-quality healthcare, reducing unnecessary medical interventions, and addressing the social determinants of health. The COVID pandemic also teaches us a lesson that we must not forget that during a pandemic pregnant women may be scared to deliver their babies in environments that do not offer the safety that mothers are looking for when it is time to deliver their infant. Hospitals that are filled with patients that are affected by the pandemic are not the ideal safe place a mother needs, so we should plan for future pandemics to have midwife services available to those women, or to have small clinics, not connected to hospitals, where women can safely deliver their babies.

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REFERENCES

1. World Health Organization. (2019). Maternal mortality. https://www.who.int/news-room/fact-sheets/detail/maternal-mortality
2. United Nations Population Fund. (2019). Maternal Health. https://www.unfpa.org/maternal-health
3. United Nations. (2015). Sustainable Development Goals: Goal 3: Ensure healthy lives and promote well-being for all at all ages. https://www.un.org/sustainabledevelopment/health/
4. Say, L., et al. (2014). Global causes of maternal death: a WHO systematic analysis. The Lancet Global Health, 2(6), e323-e333.
5. World Health Organization. (2016). Strategies toward ending preventable maternal mortality (EPMM). https://www.who.int/maternal_child_adolescent/topics/maternal/epmm/en/
6. United Nations Population Fund. (2017). The State of the World’s Midwifery 2017: The Power of Midwives. https://www.unfpa.org/swop-2017
7. Ahmed, S., et al. (2015). Challenges in reducing maternal mortality in Pakistan: the need for focus on skilled attendance at delivery. PloS One, 10(4), e0119190.
8. Villar, J., et al. (2016). Maternal and neonatal individual risks and benefits associated with caesarean delivery: multicentre prospective study. BMJ, 354, i4711.
9. Campbell, O. M., & Graham, W. J. (2006). Strategies for reducing maternal mortality: getting on with what works. The Lancet, 368(9543), 1284-1299.
10. Kassebaum, N. J., et al. (2016). Global, regional, and national levels of maternal mortality, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. The Lancet, 388(10053), 1775-1812.
11. Lancet Global Health. “Impact of the COVID-19 pandemic on maternal and child health.” 2021. https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00090-2/fulltext

Premature birth is defined as a birth that occurs before 37 weeks of pregnancy. Your baby is a preemie if born prematurely, and it may take longer for you to be able to take your preemie home compared to full-term babies. The time frame for a premature baby to go home depends on several factors including their gestational age, weight, and overall health.

Here are the typical milestones that a premature baby needs to reach before they can go home:

• WEIGHT: the preemie baby needs to reach a stable weight, usually around 1.8-2.3 kg so that they can maintain their body temperature and feed on their own.
• TAKE ALL FEEDINGS BY MOUTH: preemie babies often have immature digestive systems and typically start out by being nourished with total parenteral nutrition (TPN), which is an IV fluid that provides all the nutrition that they need. Next, they will be fed through a feeding tube until they are strong enough to suck on the breast or drink from a bottle. These problems need to be resolved before going home.
• OUTGROW THE As AND Bs: As and Bs refer to apnea and bradycardia in preemie babies. Apnea is when a baby stops breathing for over 20 seconds, causing low oxygen levels and a lower heart rate (bradycardia). This is common in premature babies, occurring in nearly half of the babies born at 30 weeks gestation and declining to 7% by 34-35 weeks. Preemies under these conditions stay in the NICU until the condition improves, and when they are stable and meet other criteria, they may be allowed to go home.
• BREATHE WITHOUT SUPPORT: some preemies may need respiratory support soon after birth, while others will only need extra oxygen. Your preemie baby should be able to breathe room air without oxygen before going home. 
• MAINTAIN A STABLE  BODY TEMPERATURE: preemies with low body fat need to be kept warm and start their lives in an incubator. They can start being trialled out of an incubator as small as 1.5kg, but some may not be able to maintain their temperature outside of the incubator until they reach 1.8-2.3 kg. The infant must maintain a body temperature of 36.3-37.4 degrees outside of the incubator before they can go home.
• INFECTION CONTROL: preemie babies have a weaker immune system, so it is important to ensure they are free from infections before going home.
• NO MEDICAL SUPPORT NEEDED: preemies may require medical support such as oxygen therapy, tube feeding, or medication. Once they no longer need these interventions, they can be considered for discharge.

The exact time frame for your preemie baby to go home will depend on their individual situation. Your doctor will closely monitor their progress and give you updates on when they can be discharged.

In conclusion, the goal is to ensure that your preemie baby is healthy and ready for discharge before going home. This will ensure a smooth transition and reduce the risk of complications.

Do social and economic disparities, within the same country, determine different prematurity risk levels? In other words, are pregnant women with lower income or living in a socially and economically disadvantaged environment more likely to give birth to a preterm baby?

Several studies show that the answer is yes!

Let’s consider the USA, for instance. The first data to be pointed out is that more than 10 percent of babies born in the USA are preterm, which is a quite high rate for an industrialized and developed country. This rate has been steadily growing in the last years, and in 2020, for the first time in six years, it declined slightly from 10.2% to 10.1% (2021 March of Dimes Report Card). Amongst the potential reasons identified for this high rate we can mention a general lack of prenatal care, obesity, tobacco use and fertility treatments, which can all lead to early births.

What is really astonishing is the large inequalities striking women based on their socio-economic status, and also on their ethnicity. Preterm birth rate among black women is 51% higher than the rate among all other women. Black women have on average 14% preterm birth rates, compared to 9.2% of white women. American Indians and Alaska natives have the second highest rate (11.7%), followed by Hispanic women (9.8%). The same disparity exists for what concerns preterm deaths. While the overall US infant mortality rate is 5.6 every 1,000 live births, for black women this rate reaches 10.9 per 1,000 births, almost doubling the average, compared to the 4.7 rate in white women, and 5.2 for Hispanic, while American Indians and Alaska natives stand at 8.6.

The causes must be searched in socio-economic factors which are also determinants of health, and are heavily impacted by racial and ethnic disparities. Amongst such determinants, the income level as well as the poverty rate of the area where the mothers live have been both associated to prematurity risk.

Income inequality is a factor of major concern, since the economic divide in the USA is the largest since 1928. A 2016 study [Wallace] examined the risk of preterm birth in the context of increasing income inequality. By collecting data related to 12 States in the USA with almost 230,000 live births over 6 years, the study showed that any increase in state-level income inequality from the year prior to birth was associated with an independent 7% increased risk of preterm delivery. Women who were pregnant in an area where inequality was increasing were more likely to give birth preterm.

Another study [De Franco] investigated the independent effect of county-level poverty on preterm birth risk. By analysing almost 635,000 live births in 155 counties in Missouri, the study concluded that women living in counties with the highest poverty rate were 1.30 times more likely to deliver preterm infants.

Socio-economic factors, low income, racial and ethnic inequalities can also be considered for explaining the significantly different preterm rates between developed countries. For instance, in the USA, South-Eastern States have higher rates, reaching even 14.2% in Mississippi, 12.9% in Alabama and Louisiana, 11.8% in Arkansas, compared to 8.6% in Washington, 8.8% in California, and 9.2% in New York (US average at 10.1%). In Europe, prevalence rates of preterm birth range from 5.4 to 12.0%, from less than 6% in Finland, Latvia, Estonia, Sweden, and Lithuania, to more than 8% in Belgium, Germany, Hungary, Greece (European average at 7.3%).

Therefore, even in countries with comparable levels of development and healthcare systems, preterm birth rates vary significantly, and several reasons have been explored. For instance, a 2015 study [Delnord] on the disparities in the preterm birth rate in European countries indicated modifiable population factors – BMI, smoking, and environmental exposures – as well as medical practices and policies related to infertility treatments as impacting factors on country-level preterm birth rates.

A lot of knowledge gaps exist around prematurity, and still the causes of preterm birth remain unidentified in up to half of all the cases. But evidence collected on the effect of socio-economic and racial inequalities on preterm birth rates and preterm deaths between countries and within the very same country should more and more direct governments’ intervention strategies to fight prematurity. Such strategies clearly need to include actions to ameliorate conditions of poverty and reduce income disparity, and also to reinforce antenatal and postnatal care in low-income countries and in the most disadvantaged areas of developed countries.

The WHO stated that more than three-quarters of preterm infants could be saved with feasible, cost-effective care, and further reductions are possible through intensive neonatal care. The mission of our Preemie system is to contribute to this fundamental goal, by making it possible to ensure personalized nutrition to each preterm infant, wherever in the world.

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Bibliography

DeFranco, Emily A, et al., Area-level poverty and preterm birth risk: A population-based multilevel analysis, BMC Public Health 2008, 8:316 doi:10.1186/1471-2458-8-316.

Delnord, Marie et al., What contributes to disparities in the preterm birth rate in European countries?, Curr Opin Obstet Gynecol 2015, 27:133–142 doi:10.1097/GCO.0000000000000156

Wallace, Maeve E., et al., Preterm Birth in the Context of Increasing Income Inequality, Matern Child Health J. 2016 January ; 20(1): 164–171. doi:10.1007/s10995-015-1816-9.

WHO, Born Too Soon, The Global Action Report on Preterm Birth, 2012.

January 20th, 2022 – London, England: New article on cost-benefit analysis of Targeted Fortification by Preemie System is published in Neonatal Intensive Care Journal

The team of Preemie System is happy to announce that a recent article on the cost-effectiveness of the Targeted Fortification Approach for very low birth weight infants (VLBF) has been accepted and published in the Neonatal Intensive Care Journal, Volume 35, No. 1 Winter 2022. 

The article was researched and written by Paolo Satta, Isabel Hoffmann, and Diogo Barros, and is a comprehensive study on the cost-benefit analysis of Targeted Fortification. It quantifies the total costs versus the economic benefits of Targeted Fortification over Standard Fortification. 

Human milk is the ideal nutrition recommended for all very low birth weight infants. However, human milk is highly variable in nutrient content and does not address the nutritional needs of this group of infants. Fortification of human milk is recommended in order to prevent extrauterine growth retardation and associated poor neurodevelopmental outcomes. Standard Fortification, performed with fixed doses of a multicomponent fortifier, does not account for the variability in milk composition, but it is less costly than Targeted Fortification, where fortifiers are added to breast milk based on the results of breast milk analysis.

Based on the analysis of selected studies that pointed out the clinical outcomes obtained when adopting the Targeted Fortification approach, the article raises the awareness that Targeted Fortification, although more expensive to implement than Standard Fortification, has far superior clinical outcomes and can effectively prevent several very costly diseases associated with malnutrition, proving to be a much better cost-effective solution for feeding very low birth weight infants. 

“We are very pleased to have our article published in the well-renowned Journal of Neonatal Intensive Care in the USA.” remarked Isabel Hoffmann, CEO of Tellspec LTD, the company that developed the Preemie System. “Because it shows that the Preemie System helps decrease the overall cost of care for very low birth weight infants, despite the added cost of Preemie Sensor, the associated software, and the extra time to perform Targeted Fortification.” 

For more information or inquiries, please contact us at info@preemiesystems.com.

In order to access the article stated on page 56 of the Neonatal Intensive Care magazine (Vol. 35 No. 1 Winter 2022), Please contact us at info@preemiesensor.com to obtain further information on this article.

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ABOUT PREEMIE SYSTEMS
The Preemie System is the first clinical AI platform to deliver optimal infant-centric feeding and care. It also offers an end-to-end solution to individualized, targeted fortification by analyzing the unique chemistry of human milk with the use of rapid, reliable, and cost-effective sensor, and dedicated AI-based software. Preemie’s software also tracks and reports information about infant growth and its correlation to the milk fortification given.

Several studies have been executed so far to assess the benefits of the targeted fortification approach when compared to the standard approach currently adopted (see Fabrizio 2020 for a recent review). These studies allowed us to appreciate the potentiality of targeted fortification in improving the clinical outcomes for preterm infants.

While standard fortification poses the infants at risk of not getting the recommended intake, due to the lack of knowledge of the actual macronutrient content in the administered human milk, the targeted approach allows neonatologists to fortify the milk based on the actual milk content, which implies that the feeding given is tailored to the specific infants’ need.

Amongst the most promising results evidenced so far, infants fed with the targeted approach experience higher macronutrient intakes, higher weight gain and in general improved growth velocities for what concerns weight, length, and head circumference. They also show higher fat-free mass and less frequent feeding intolerance. Such results are due to a limited variation of macronutrient intake, which allows for a more balanced and constant diet. Infants get similar composition every day, avoiding the administration of lots of proteins or fat on one day, and less proteins or fat the other day, thus posing less stress on their premature gut and metabolism. Such outcomes have been recently linked to a reduced neonatal morbidity, in particular for what concerns the occurrence of NEC, sepsis and bronchopulmonary dysplasia (see Rochow 2020 and Sánchez Luna 2020). There is clearly the need to confirm those results, and above all quantify them, through specifically designed interventional trials. Meanwhile it’s not surprising that an increasing number of hospitals and neonatologists is implementing the targeted approach for managing the feeding of preterm infants.

But there is also the other side of the coin: compared to the standard approach, targeted fortification is more time-consuming, requires the purchase and maintenance of specific equipment for analysing human milk, and also trained staff for both operating the device and for calculating the fortification needed. Rochow 2015 estimated an average of 10-15 minutes per patient per day for applying this approach, which clearly raises the overall operational costs of the nursery.

In order to contain such costs and make the targeted approach sustainable in all nurseries, studies have been performed to assess the most cost-effective frequency of human milk analysis, trying to minimize as much as possible the macronutrient variation in infants’ feeding from day to day, but also reducing the workload for operators. For instance, Rochow 2015 suggested to perform human milk analysis “at least twice a week” as an optimal trade-off.
So, if we consider both benefits and costs, the big question is: is the targeted approach really cost-beneficial? To give an accurate answer, specific health economics studies are needed, where costs for implementation and maintenance of such an approach are compared to economic quantification of evidence-based benefits (for instance, savings generated by reducing the length of stay or key diseases, such as NEC).

Far from being an exhaustive article on this topic, we want here just to highlight a few available data aimed to provide a sense of the potential savings that could be generated by applying the targeted approach.

• Reduction of length of stay. Several studies mentioned this potential benefit (see Rochow 2015), even if this has not been confirmed yet in the trials performed so far. The cost per hospitalization day varies from Country to Country, and even amongst hospitals in the same area. We take as a reference two studies performed by Johnson (2013 and 2015), where the average cost per hospitalization day of a VLBW infant was estimated respectively at $1,052 and $1,874. A hospital serving an average of 100 infants per year would therefore get significant savings even with just a 1-day reduction of the length of stay per infant (between $100,000 and $180,000).、

• Reduction of parenteral nutrition. A more balanced diet in line with the targeted requirements may help in a faster switch from parenteral to enteral nutrition. Savings could be quite significant, if we consider that around $1,436 is spent daily per patient receiving parenteral feeding (Edwards 2012). In the use case of the previous point, savings per year could therefore reach around $143,000 in case of just 1-day reduction of parenteral feeding per infant.

• Reduction of diseases during hospitalization. Since infants are fed with basically the same macronutrient composition over time, their gut works under more steady condition, and this is considered a factor for reducing the occurrence of specific diseases. This is going to be studied in upcoming clinical trials (see Seliga-Siwecka 2020), while other studies reported a reduction of specific diseases (see Sánchez Luna 2020). Let’s consider three diseases whose reduction has been mentioned in such studies: NEC, sepsis and bronchopulmonary dysplasia. The costs for those diseases have been reported in various studies. In Johnson 2015 reported an average total NICU hospitalization cost (in 2012 dollars) of $180,163 per infants with NEC and $134,494 for infants without NEC. NEC was associated with a marginal increase in costs of $43,818. Johnson 2013 reported that the presence of bronchopulmonary dysplasia was associated with a $31,565 increase in direct costs, and late-onset sepsis with a $10,055 increase. Any assumptions on the reduction rate would be completely arbitrary at this point, but imagine that just one case of each disease is avoided every year in a hospital. This will make savings up to more than $85,000 every year.

• Long-term economic benefits. Savings in this area are clearly the most complex to be demonstrated and quantified, since they require the quantification of savings on clinical complications after hospitalization and on potentially life-long morbidities. One focus of the analysis could be related to the long-term benefits (and related savings) due to avoiding under- and over-nourishment caused by the standard approach. Another example is related to avoiding neurological impairment, due to optimal growth and to the reduction of infants’ morbidities during the hospitalization period. Let’s make a some reasonings related to the latter point.
  A key point is related to the “quality” of the weight gained during the hospitalization period. Parat 2020 showed that “targeted fortification of milk can influence the quality of weight gain through promoting fat-free mass in infants”, and early gain in fat-free mass has been demonstrated to generate positive long-term effects, unlike fat mass. Ramel 2016 demonstrated the association of fat-free mass at discharge with improved neurodevelopment in VLBW preterm infant at 12 months, while Scheurer 2018 showed that high percentage of fat mass is associated with lower-working memory performance in pre-school age (4 years). Another study (Frondas-Chauty 2018) demonstrated that a deficit of fat-free mass at discharge is associated with neurological impairment at two years of age.
  Neurodevelopment impairment has also been demonstrated to more likely occur in infants who had NEC or sepsis (diseases that the targeted approach could reduce) than in preterm infants without such morbidities (see Rees 2006 and Cai 2019). Conditions such as cerebral palsy, vision impairment or hearing impairment could be reduced thanks to the optimal growth promoted through targeted fortification, or indirectly by reducing the occurrence of diseases that make such impairment more likely in a later age. And their costs are not negligible. Honeycutt 2015 showed that lifetime costs per person for cerebral palsy are around $804,000 (in US$ 2000), for hearing loss at $325,000 and for vision impairment at $469,000. This gives us a sense of how large the life-long savings could be both for the society and for the patients.

So, a lot of work is still needed to precisely quantify the economic benefits of the targeted approach through evidence-based studies, but the more our knowledge advances in this field, the more targeted fortification seems to provide promising results.

We therefore want to conclude this blog by mentioning Sánchez Luna 2020. The study reports the benefits coming from the establishment of a personalized nutrition unit (PNU), based on a smart management of mother’s milk and the application of targeted fortification. This approach led to “a significant reduction of NEC in preterm infants of < 32 weeks of gestation, from 10.9% (12/110) to 2.4% (2/84), and late-onset sepsis from 14.7 cases/1,000 days of central lines to 9.5 cases/1,000 days of central lines, with a shorter use of central venous catheters for parenteral nutrition and a better growth during hospitalization”.

We are firmly convinced that similar studies and their promising results will multiply in the near-future, not only evidencing the unique clinical benefits that the targeted approach can guarantee to preterm babies, but also demonstrating that the approach is sustainable and economically beneficial in both the short and long term. The path seems really to be market out, and Preemie is proud to give its contribution to this radical change.

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REFERENCES

Fabrizio 2020 – Fabrizio V, Trzaski JM, Brownell EA, Esposito P, Lainwala S, Lussier MM, Hagadorn JI. Individualized versus standard diet fortification for growth and development in preterm infants receiving human milk. Cochrane Database of Systematic Reviews 2020, Issue 11. Art. No.: CD013465. DOI: 10.1002/14651858.CD013465.pub2.

Rochow 2020 – Niels Rochow, Gerhard Fusch, Anaam Ali, Akshdeep Bhatia, Hon Yiu So, Renata Iskander, Lorraine Chessell, Salhab el Helou, Christoph Fusch. Individualized target fortification of breast milk with protein, carbohydrates, and fat for preterm infants: A double-blind randomized controlled trial. Published by Elsevier Ltd. 2020, https://doi.org/10.1016/j.clnu.2020.04.031.

Sánchez Luna 2020 – Manuel Sánchez Luna, Sylvia Caballero Martin, Carmen Sánchez Gómez-de-Orgaz. Human milk bank and personalized nutrition in the NICU: a narrative review, European Journal of Pediatrics, 2020, https://doi.org/10.1007/s00431-020-03887-y

Rochow 2015 – Niels Rochow, Gerhard Fusch, Bianca Zapanta, Anaam Ali, Sandip Barui and Christoph Fusch. Target Fortification of Breast Milk: How Often Should Milk Analysis Be Done?, Nutrients 2015, 7, 2297-2310; doi:10.3390/nu7042297

Johnson 2013 – Tricia J. Johnson, Aloka L. Patel, Briana J. Jegier, Janet L. Engstrom, and Paula P. Meier. Cost of Morbidities in Very Low Birth Weight Infants. THE JOURNAL OF PEDIATRICS, Vol. 162, No. 2, 2012. DOI:https://doi.org/10.1016/j.jpeds.2012.07.013

Johnson 2015 – Tricia J. Johnson, Aloka L. Patel, Harold R. Bigger, Janet L. Engstrom, and Paula P. Meier. Cost Savings of Human Milk as a Strategy to Reduce the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Infants. Neonatology. 2015 ; 107(4): 271–276. doi:10.1159/000370058

Edwards 2012 – Taryn M. Edwards, Diane L. Spatz. Making the Case for Using Donor Human Milk in Vulnerable Infants. Adv Neonatal Care. 2012 Oct;12(5):273-8; quiz 279-80. doi: 10.1097/ANC.0b013e31825eb094.

Seliga-Siwecka 2020 – Joanna Seliga-Siwecka, Anna Chmielewska and Katarzyna Jasińska. Effect of targeted vs standard fortification of breast milk on growth and development of preterm infants (≤ 32 weeks): study protocol for a randomized controlled trial. Trials (2020) 21:946 https://doi.org/10.1186/s13063-020-04841-x

Parat 2020 – Sumesh Parat, Praneeta Raza, May Kamleh, Dennis Super and Sharon Groh-Wargo. Targeted Breast Milk Fortification for Very Low Birth Weight (VLBW) Infants: Nutritional Intake, Growth Outcome and Body Composition. Nutrients. 2020 Apr 21;12(4):1156. doi: 10.3390/nu12041156.

Ramel 2016 – Sara E. Ramel, Heather L. Gray, Ellen Christiansen, Christopher Boys, Michael K. Georgieff, and Ellen W. Demerath. Greater Early Gains in Fat-Free Mass, but Not Fat Mass, Are Associated with Improved Neurodevelopment at 1 Year Corrected Age for Prematurity in Very Low Birth Weight Preterm Infants. J Pediatr. 2016 Jun;173:108-15. doi: 10.1016/j.jpeds.2016.03.003. Epub 2016 Apr 4.

Scheurer 2018 – Johannah M. Scheurer, Lei Zhang, Erin Plummer, Solveig Hultgren, Ellen W. Demerath, Sara E. Ramel. Body Composition Changes from Infancy to 4 Years and Associations with Early Childhood Cognition in Preterm and Full-Term Children. Neonatology 2018;114:169–176 DOI: 10.1159/000487915

Frondas-Chauty 2018 – Anne Frondas-Chauty, Laure Simon, Cyril Flamant, Matthieu Hanf, Dominique Darmaun, and Jean-Christophe Rozé. Deficit of Fat Free Mass in Very Preterm Infants at Discharge is Associated with Neurological Impairment at Age 2 Years. J Pediatr. 2018 May;196:301-304. doi: 10.1016/j.jpeds.2017.12.017.

Rees 2006 – Clare M Rees, Agostino Pierro, Simon Eaton. Neurodevelopmental outcomes of neonates with medically and surgically treated necrotizing enterocolitis. Arch Dis Child Fetal Neonatal Ed 2007;92:F193–F198. doi: 10.1136/adc.2006.099929

Cai 2019 – Shirley Cai, Deanne K. Thompson, Peter J. Anderson, and Joseph Yuan-Mou Yang. Short- and Long-Term Neurodevelopmental Outcomes of Very Preterm Infants with Neonatal Sepsis: A Systematic Review and Meta-Analysis. Children (Basel). 2019 Dec; 6(12): 131. doi: 10.3390/children6120131

Honeycutt 2015 – Amanda A Honeycutt, Scott D Grosse, Laura J Dunlap, Diana E Schendel, Hong Chen, Edward Brann, Ghada al Homsi. “ECONOMIC COSTS OF MENTAL RETARDATION, CEREBRAL PALSY, HEARING LOSS, AND VISION IMPAIRMENT” In Using Survey Data to Study Disability: Results from the National Health Survey on Disability. Published online: 10 Mar 2015; 207-228.