Birth-related decisions principally center on safety; giving birth during a pandemic brings safety challenges to a new level, especially when choosing the birth setting. Amid the COVID-19 crisis, the concurrent work furloughs, business failures, and mounting public and private debt have made prudent expenditures an inescapable second concern. This article examines the intersections of safety, economic efficiency, insurance, liability and birthing persons’ needs that have become critical as the pandemic has ravaged bodies and economies around the world. Those interests, and the challenges and solutions discussed in this article, remain important even in less troubled times. Our economic analysis suggests that having an additional 10% of deliveries take place in private homes or freestanding birth centers could save almost $11 billion per year in the United States without compromising safety. Births at home or in a freestanding birth center were increasing in the US even before COVID-19, but since decisions around birth generally center on safety, giving birth during this pandemic has brought safety challenges to a new level. As hospitals began to apply COVID restrictions, increasing numbers of childbearers made the decision to be supported during labor by their partners in their private homes See –4, insteFurthermore, amid the COVID-19 crisis, the concurrent work furloughs, business failures, and mounting public and private debt have made unnecessary personal and community/state expenditures an inescapable concern. For years, maternity and newborn care have constituted the largest hospital payouts from commercial insurers and state Medicaid programs, and the per-capita expenditures in the United States exceed those in every other high-resource country . Before As we will detail in this article, birthing persons have been continually achieving safe outcomes in private homes and freestanding birth centers with the assistance of midwives in the United States and abroad. Even so, there has been reluctance to include all nationally credentialed midwives in publicly funded US maternity care programs and state licensure policies. Resistance stems from beliefs that home or freestanding birth center births are riskier than hospital birthsCOVID-19 has disrupted the perspective of actual safety because staying at home offers better protection from the pandemic for childbearers than sharing a hospital with disease-stricken patients. While freestanding birth centers, unlike hospitals, are not the settings where COVID-19 positive individuals go for treatment, they still present the risk of contamination from other patients, staff, and visitors. Yet as at hospitals, practitioners providing care in private homes and freestanding birth centers can take safety measures that include masks, sanitizing measures, and a minimized number of people at the birth –2, as otwithout necessitating trade-offs regarding safety. This is the first study to estimate the specific savings from public policy that increases births in private homes or freestanding birth centers by a given percentage. We intend to demonstrate that greater access to maternity care by credentialed and licensed midwives in these settings is a solution that is safe, cost effective, and increasingly popular.The economic analysis of public policy is usually a struggle with trade-offs. Consider a policy that increased the speed limit. It would save time, the trade-off being a predictable increase in traffic fatalities and carbon emissions. Yet in this article, we demonstrate how a public policy that expanded midwifery in the United States could save billions of dollars For practical models, we can draw on the experiences of countries that have invested in publicly funded home and freestanding birth center births. For example, starting in the 1980s, the Canadian provincial governments charged lawyers and consultants to research a birth model that was safe, cost effective, and met the needs that childbearers were asking for. The solution: to give midwives legislative support and require the provision of a range of birth settings. Almost all provinces have implemented midwifery legislation since it was established in the province of Ontario in 1993. Now 11% of Canadian births are attended by midwives, and in the two provinces with the most midwives—B.C. and Ontario—25 and 15% of births respectively are under midwifery care . Midwive(1) The statements on home birth during the last four years by the American College of Obstetricians and Gynecologists  have acknowledged women’s right to choose and agreed that home birth is safe in countries with well-integrated midwifery systems;(2) Faced with the pandemic, an emergency Executive Order by Governor Cuomo of New York State permitted midwives licensed in other states or Canadian provinces, including Certified Professional Midwives, who had long been illegal in New York, to practice legally there for the initial period of major outbreak in the state (Executive Order #202.11). The timeline has continued to be extendedTwo major breakthroughs in the last four years have occurred suggesting that former opponents to home birth and to the use of a specific group of midwives, Certified Professional Midwives (CPMs) may have softened their views:To be clear, Certified Professional Midwives (CPMs) are the only US midwives whose educational standards require them to undergo specialized clinical training in private homes or freestanding birth centers as a condition of national certification. They are also the only US midwives who are not allowed to practice in hospitals, and they can practice legally in only 36 states, with legislation pending in others.The pressing questions now are: Will the gaps in the US maternity care system, and the solutions generated during COVID-19 be recognized as important when the pandemic is gone? Will increasing the numbers of midwives trained to work in private homes and freestanding birth settings and fully integrating them into that system during COVID-19 finally be recognized as a paradigm shift that will serve birthing people in normal times?safety and economic efficiency of birth in private homes and freestanding birth centers, which has become even more critical as the coronavirus ravages bodies and economies around the world. We contend that those interests, and the solutions of increased legislation, liability insurance, and better integration for midwives working in those settings remain important even in less troubled times.In what follows, we examine the intersection of the After a gradual decline from 1990 to 2004, the number of out-of-hospital births in the US increased from 35,578 in 2004 to 62,228 in 2017, so that 1 of every 62 births took place in homes and freestanding birth centers (1.61%) . By 2015Who is available to provide births outside the hospital in the US? Certified Nurse-Midwives (CNMs) attend births primarily in hospitals; in 2018, 9,399—only 2.6% of the births that they attended were in private homes and 11,139 (5.1%) in freestanding birth centers . MedicaiIn 2018, CPMs and other midwives who are not CNMsI have served as a collaborative physician for several CNMs making the transition from hospital to home birth practice and have seen how steep the learning curve is, especially in their first year. To focus on safety in home and birth center birth, then we have to admit that it requires a different skill set than hospital birth and that providers practicing in the community setting must be trained in that skill set to maintain the safety of the environment .It is important to emphasize that births attended in private homes and freestanding birth centers require providers specifically trained to do so with proper equipment, protocols in place for transport to hospital, and back up hospitals pre-arranged. As one physician reports:Although many Americans have assumed that more CNMs could start doing home births if they so desired, it appears difficult for the US administrative facilities to consider something the other way around--that CPMs could work in hospitals. Because Canada deliberately chose not to create distinctions between nurse-midwives and other midwives at legislation, it is rare that Registered Midwives in Canada are also nurses. Yet all midwives in the standard Canadian model must have hospital privileges and do at least some hospital births, as well as home births.In Canada, in the US states that have legislated and adopted insurance coverage for CPMs, and in other countries that have discovered or continued to recognize the importance of midwives who provide care in the community outside the hospital, a critical commonality has emerged. Bringing these midwives out from underground economies to have them fully integrated into what the World Health Organizations calls “the Reproductive, Maternal, Newborn and Child Health (RMNCH) Continuum of CareIn the US in 2018, midwives attended 10.2% of births , with a The two most recent meta-analyses examining perinatal outcomes for birthing people with low-risk pregnancies in high-income countries have demonstrated similar levels of safety for hospital and planned, midwife-attended births in private homes or freestanding birth centers. An Australian meta-analysis  found noA 2019 Canadian meta-analysis found 14 eligible international studies—representing more than 500,000 home births—which met their strict criteria for comparing planned home to planned low-risk hospital birth . StratifIn less integrated settings, Despite limited institutional support for credentialed midwives in the United States attending births in private homes and freestanding birth centers, the weight of evidence in US cohort studies indicates that births in these settings have good outcomes when the studies: 1) are based on charts rather than birth certificates, because the latter often lack accurate outcome and care details; 2) identified low-risk women; 3) are able to discern the planned place of birth, thereby avoiding counting accidental, unplanned out-of-hospital births; and 4) are conducted on a defined group of midwives with training standards. Where comparisons are possible, these US cohort studies , produceThis section demonstrates that births in homes and freestanding birth centers are far less expensive to society than hospital births. Combined with the evidence that outcomes are similar among low-risk mothers who plan their births in private homes, birth centers, or hospitals, this fact reveals a win-win situation: childbearers choosing their own home or a freestanding birth center can have the safety of hospital births at a fraction of the cost to families or insurers. The relevant discussion, then, is about whether the size of the “win” is worthwhile.There are approximately 3.9 million births annually in the United States . The aveIn the Scarf meta-analysis (2018), women planning a hospital birth were nearly three times as likely to have a cesarean or instrumental (forceps or vacuum) delivery as those planning a home birth, and nearly twice as likely to have a cesarean as those planning a birth center birth. Similarly, there has been consensus across the literature for decades that planned home and birth center births in the United States entail significantly less medical intervention than planned hospital births .Our cost analysis of interventions focuses on cesareans because they are both the costliest intervention and the cause of numerous safety concerns. Cesareans are associated with a two-fold increase in maternal mortality, increased maternal blood loss, impaired neonatal respiratory function, increased incidence of maternal postpartum infections, increased fetal lacerations, trouble with maternal-infant interaction, extended length of stay and recovery, re-hospitalization, placenta accreta and previa, hysterectomies, transfusions of ≥4 units, maternal ICU admission, and uterine rupture . It is bAlthough the risk of a serious problem during a typical cesarean birth is low, with almost one-third of US births being cesareans, problems occur and costs are high. The cesarean rate for planned hospital births in the United States is 32% , compareA cesarean adds an average of $5,735 to the cost of a birth in the United States . With thWhen prenatal care is provided by credentialed midwives, the incidence of low birthweight decreases. For example, the rate decreased from 2.4 to 1.1% in a national study  and fromCompetition is a moderating force for prices and an incentive for improved quality. We like to emphasize that competition is valued as an economic concept because it reduces costs and increases access and quality of goods and services for consumers. As the Big Push for Midwives Campaign posted on social media December 30, 2020,The Big Push for Midwives is a national campaign in the US initiated and driven by consumers wanting to increase access to care by midwives attending births in the broader community, not just in the hospital. It focuses on increasing access to CPMs by pushing for legislation that legalizes them in the 14 holdout states and also on the need for CNMs to come out from the requirement of physician sign-off on their care:If stronger competition forced hospitals to reduce their price for an uncomplicated birth by 10%, the 3.51 million childbearers who would still deliver in the hospital under our scenario—or their insurersThe total estimated savings from increased access to births outside the hospital as we have described above amount to $10.868 billion annually. This proposal to facilitate an increase in births at home or in freestanding birth centers, if implemented, would represent a huge win for the many constituents who want access to safe and normal physiologic childbirth with fewer interventions, freedom of choice for a variety of ideological, religious, cultural, financial or personal reasons, and lower maternity care costs for American society.The successful implementation of US policy to increase rates of home and freestanding birth center births would be facilitated by at least tacit support from the national obstetric and public health communities. Some support has emerged: in 2001, the American Public Health Association (APHA) passed a resolution entitled, “Increasing Access to Out-Of-Hospital Maternity Care Services through State-Regulated and Nationally-Certified Direct-Entry Midwives,” after they saw the methodology and preliminary data from the “CPM 2000” study on home births .A detailed description of the history and politics behind the American College of Obstetrics and Gynecology (ACOG) statements on home birth and a rationale for better integrating midwives specializing in births at home and in freestanding birth centers in the US can be found in However, unfortunately, ACOG has not updated its analysis to include the two new home birth meta-analyses  that demA subsequent interview published between the principal author of the study, Jonathan Snowden, and Melissa Cheyney, the midwife in the state who happened to be the principal author of the national homebirth study of the Midwives Alliance of North America  clarifieBy 2016, with pressure from other obstetric associations and studies that could no longer be ignored, ACOG  accepted that home birth does occur safely in other high-resource countries and that “a characteristic common to those cohort studies reporting comparable rates of perinatal mortality” among care settings is the provision of care by midwives “well integrated into the health care system.”In their 2016–2020 statements , ACOG also acknowledged that they would support the provision of care, not just by CNMs and CMs but by all midwives whose education and licensure meet the International Confederation of Midwives (ICM) Global Standards for Midwifery Education, which many CPMs doThen COVID-19 Struck: Highlights Even More, Need for Legislation and Health Insurance for Birth Outside Hospitals.The other two ACOG statements on birth setting since COVID-19 will be discussed in Listening to Mothers survey carried out by the Less than 1 in 10 survey participants used either midwives or labor doulas … for their recent births. However … over 1 in 6 women would definitely want midwives or labor doulas for a future birth. In addition, more than 1 in 3 would consider using these care team membersIn the 17.Some of this was the result of the lack of options of available insurance providers. For example, nearly 1 in 4 Black or Latina women had their prenatal care provider assigned to them, apparently by their primary provider, compared to less than 1 in 8 white womenThe financial impediment may explain some of why data from the National Vital Statistics database demonstrate that white women have 2 ½ times the rate of home births as American Indian or Alaskan Native women, three times the rate of Black women, and almost four times the rate of Hispanic women . .The current President of the Midwives Alliance of North America, Sarita Bennett, emphasizes that there is a balancing place in US society for those not ready to choose birth in their own home but do not want to go to a hospital, especially during the pandemic:Pain relief is a major concern of birthing persons, may determine where they seek care, and is related to delivery cost. In the national Listening to Mothers survey of 2013, 67% of respondents used epidural or spinal analgesia, 16% used narcotics, and 7% were given general anesthesiaSome childbearers want to be more physically involved with their births and have fewer interventions. In the same survey, 17% said they used no pain medication, and 6% used nitrous oxide (the same “laughing gas” that dentists use), which is a client-controlled and effective method of pain relief and can be made available in birth centers and at home births. It is cheaper for birthing persons to use nitrous in home or birth centers, as hospitals can take advantage of the lack of regulation to charge what they want. For example, a hospital in Wisconsin bills more than $100 for every 15 minutes that the nitrous is sitting in the room, which, for one woman, resulted in a bill of $4,836, whereas the local freestanding birth center charges only a flat fee of $100 for its use, for as long as it is needed. An epidural in the same hospital in Wisconsin costs $1,500, a third of the price of the nitrous oxideListening to Mothers national survey, women reported using a variety of drug-free methods to increase comfort and relieve pain, with 73% using at least one non-pharmacologic method of pain relief, led by breathing techniques (48%), position changes (40%), hands-on techniques like massage (22%), and mental strategies  (21%)18.In the aforementioned 2013 A birthing person’s ability to pay for a birth in their private home or at a freestanding birth center is often limited by finances because most hospital births are paid for through public or private insurance, while births not in hospital are rarely afforded the same privilege. In 2017, more than 2/3 (67.9%) of planned home births and almost 1/3 (32.2%) of birth center births were paid for by the birthing persons themselves, while only 3.4% of women self-paid for hospital births .Models for increasing access to birth settings for low-risk women that have been implemented at the state level include expanding Medicaid, Medicare, and commercial payer coverage to cover care provided at home and birth centers … by certified nurse midwives, certified midwives, and certified professional midwives whose education meets International Confederation of Midwives Global Standards … the potential impact of these state-level models is needed to inform consideration of nationwide expansion, particularly with regard to effects on reduction of racial/ethnic disparities in access, quality and outcomes of care  maternity care, which is far from a living wage. Of course, these issues need to be addressed in order to create the access for birthing families that is so desperately needed .Vicki Hedley, Past-President of the Midwives Alliance of North America (MANA) and Senior Advisor to NYCPM—the New York State CPM organization—thinks that COVID-19 holds hope for change but explains the complications:There is currently a proposal for licensure of CPMs in New York being drafted by the office of Dick Gottfried, the Chair of the Assembly Health Committee. It needs some better language before being submitted and the midwives are trying to communicate with the office about it. It is the optimum time to present a bill with several months of “legal” status during the pandemic already. The executive order is renewed monthly, but that means only that midwives with a license in another state can practice legally until that expiration date. Midwives and clients need more certainty than one month of legal status! Meanwhile, the temporary nature of the Governor’s Executive Order has caused serious problems for any CPM who does want to practice in the state to meet the increased demand by mothers and families for out-of-hospital birth options. Ida Darragh, the Executive Director of the North American Registry of Midwives (NARM), the organization responsible for setting standards for CPM credentialing nationally, describes the urgent need for legislation:This ambiguous month-to-month situation puts the CPMs currently practicing in New York in a vulnerable state: being legal for a few months, but then with the potential to have their licensure removed just when their clients are actually due to have their babies!remain safe places to give birth in the United StatesACOG and ACNM recognized early on that the pandemic had created an interest in home birth, alerting them to the fact that families were nervous about institutional birth settings. They issued a joint statement in March acknowledging the pandemic but assuring the public that “Hospitals and birth centers that are both licensed and accredited hospitals and accredited birth centers remain the safest places to give birth [italics added]. Physicians, certified nurse-midwives and certified midwives, and the entire health care team will work to ensure that precautions are taken to make labor and delivery safe, supportive and welcoming for their patients  programs--has led to better quality and outcomes of care, and impressive declines in liability claims, payouts, and premium levels. A number of promising strategies warrant demonstration and evaluation at the level of states, health systems, or other appropriate entities. Rigorous QI programs have a growing track record of contributing to diverse aims of a high-functioning liability system and seem to be a win-win-win prevention strategy for childbearing families, maternity care providers, and payers. Effective strategies are also needed to assist families when women and newborns are injured.The present liability system can create insurmountable financial risks for practitioners that make them reticent to offer valued services that childbearers are increasingly seeking. A team of researchers concerned about the impact of the present system identified seven aims for a high-functioning liability system and studied “whether 25 strategies that have been used or proposed for improvement have met or could meet the seven aims” . They coCOVID-19 raises new questions about liability for midwives who practice in private homes or freestanding birth centers. If there is a shortage of legal midwives based outside of hospital in any state, whether or not they are invited to temporarily practice as in New York state, or left without legal accommodation as in Illinois, midwives from neighboring states will inevitably come to the rescue of women in need in the state, regardless of their legal status .Even if midwives are legally attending births in private homes or freestanding births centers in any given state, if they don’t have hospital privileges, the increased restrictions of COVID-19 can have serious implications. Ida Darragh and Vicki Hedley explain that many hospitals are now allowing the father of the baby to attend the birth, and just recently in some places, a doula . However, when there is a transport from a home birth, the community midwife may not be able to enter the hospital along with her own client to provide the continuity of care that is so well proven in the literature to improve outcomes . Thus imAlthough legal reform is beyond the scope of this article, we would like to point out here that there are underutilized options to discuss and disseminate transfer and practice guidelines, to encourage swift and fair settlements in legal disputes , and theHome and birth center births are on the rise in the US, and COVID-19 has provided a catalyst/pivotal moment that directs us to the need for increased access to nationally credentialed, licensed midwives and options for women to birth outside the hospital. Many US women have already switched to these options to avoid both hospital contagion and the forced choice of only one (or no) personal birthing companion during these Covidian times.As we have shown above, if only 10% more US women deliver at home or in freestanding birth centers, the savings could amount to $10.868 billion per year. Outcomes are similar for low-risk mothers regardless of setting in countries where midwives are well-trained and integrated into the Reproductive, Maternal, Newborn and Child Health (RMNCH) Continuum of Care in the communityIncreased access to credentialed maternity-care providers requires new legislation for CPM licensure in some states and extended public insurance for home and freestanding birth center settings in all states. While the data on the safety of home and freestanding birth centers has convinced the APHA and many state legislatures over the last two decades to promote birth in these settings, COVID-19 and pure practicality have convinced more state politicians of the importance of credentialed and licensed midwives who offer these alternatives to hospital birth.There are now two other important givens that mark change: First, ACOG has admitted that safe home birth is possible in other countries where midwives are well-integrated and in accredited birth centers in the US. Second, the New York State governor has invited licensed midwives, including CPMs from other states, to help out in his state during the pandemic , therebyTaking two critical further steps could integrate nationally credentialed midwives into the larger US health care system and help these midwives to meet demands of birthing people. The first is to build the infrastructure of legislation, insurance, and healthy Quality Improvement programs needed to support home, freestanding birth center, and hospital maternity care providers so they can be fully integrated into their local RMNCH Continuum of Care.The second step is to encourage a culture in which all healthcare professionals recognize and encourage each other to offer the services for which they are best suited. This would include opening rather than limiting scope of practice, eliminating physician supervision but increasing collaboration, and encouraging autonomy of midwives and clients. It would also include debunking the myths of what is “safe” and “not safe.”The first step is foreseeable and has been accomplished at least in part in about two-thirds of the United States. One would think it should be relatively easy, given the models in the other states, but of course it requires some buy-in to the second step. The second step is dependent on the first; in fact one might say the two steps are co-dependent. The second step requires visionary leaders who can turn over 100 years of conflict aside, expose the overlapping systems of self-protective competitors, and transmute the US maternity care system into a best-practice, safer and less costly model that puts the interests of the birthing population first.Whether the primary goal is safety, reproductive justice, cost savings, avoiding infection, or increasing freedom of choice and access to birth options for birthing people, public policies that support planned, midwife-attended births in private homes and freestanding birth centers are the appropriate and long overdue response.


Prefeed gastric residuals (GRs) monitoring has been correlated with an increased time to reach full feeds and longer parenteral nutrition without beneficial effect on necrotizing enterocolitis (NEC) occurrence. We aimed to assess effects of a new local protocol to provide for the selective evaluation of GRs excluding their routine monitoring.+0–31+6 weeks of gestation. The primary outcome was the age at full enteral feeding (150 mL/kg/d). Secondary outcomes included age at regaining of birth weight, and evaluation of Z-scores of weight, length, and head circumference at discharge.We carried out a retrospective study based on a “before and after” design in a cohort of infants born at 23P = 0.017) and regaining of birth weight  were lower while the Z-scores of weight at discharge  were higher in infants in the selective GR group in comparison with infants in the routine GR group.We studied 49 infants in the selective GR group and 59 in the routine GR group. Age at full (150 mL/kg) enteral feeding (17.8 ± 10.1 vs. 22.9 ± 10.5 days, Selective monitoring of GRs decreased age at full enteral feeding and at regaining of birth weight and induced better Z-scores of weight at discharge in comparison with routine GR monitoring in a cohort of extremely preterm infants without increasing the incidence of NEC. Omitting prefeed GRs monitoring in clinical practice seems reasonable.The online version contains supplementary material available at 10.1186/s13052-022-01208-7. It is cnt delay . Neverthnt delay , 12, 13.nt delay . Based o+0–31+6 weeks of gestation. Exclusion criteria were major congenital malformations, chromosomal disorders, inherited metabolic diseases, and death before reaching full enteral feeding (150 mL/kg).This center-based study was carried out at the NICU of Careggi University Hospital in Florence, Italy. Infants were included in the study if they were born at 23The new local protocol for GRs monitoring was introduced in October 2020 and routine evaluations of GRs before every feeding were discontinued. Patients undergoing selective GRs monitoring were prospectively studied from December 2020 to June 2021, while patients in the routine GRs monitoring group were retrospectively studied from December 2019 to June 2020.17.Evaluation of GRs in the selective group was performed in case of established (positive blood culture) or suspected sepsis  and consistent clinical signs and symptoms), NEC at stage 1 or higher , establiAll infants followed the same enteral nutrition protocol: trophic feeding was initiated within 24 h after birth and continued at 20–40 mL/kg/d as tolerated for up to five days. Subsequently, the amount was increased by 20 ml/kg per day if enteral nutrition was tolerated. Enteral nutrition goals were 150 mL/kg/d and 120 kcal/kg/d. All patients received their mother’s or donor’s human milk administered through an oro-gastric tube as bolus or continuous milk feeding. Human milk was enriched with a fortifier  when enteral feeding of 100 ml/kg/d was reached. Preterm formula was administered when human milk was not available. Parenteral nutrition was continued until feeds of 100 mL/kg/d were reached.The primary outcome of this study was age at full enteral feeding (150 mL/kg/d). Prespecified secondary outcomes included age at full oral (breast and bottle) enteral feeding and at birth weight recovery, duration of parenteral nutrition, stay in NICU and in hospital, and evaluation of Z-scores of weight, length, and head circumference at discharge.th percentile, antenatal steroids, mode of delivery, need and duration of non-invasive and invasive ventilation, surfactant and postnatal steroid treatment, occurrence of patent ductus arteriosus (PDA) requiring treatment, bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), mortality, duration of stay in NICU and in hospital, and occurrence of breastmilk (exclusive or mixed) feeding at discharge. BPD was defined as oxygen requirement at 36 weeks of post-menstrual age. PDA was diagnosed by echocardiography; NEC was defined as Bell’s stage ≥ 2 [Clinical and demographic data were collected by reviewing patients’ electronic medical records. The following data were recorded for each studied infant: gestational age, birth weight, birth weight < 10tage ≥ 2  sepsis wtage ≥ 2 ; ROP wastage ≥ 2 . The exatage ≥ 2 . Growth p < 0.05 was considered statistically significant.Clinical characteristics of infants in the selective and routine GRs monitoring groups were reported as mean and standard deviation, rate and percentage, or median and range. Statistical analysis was performed using the Student “t” test for parametric continuous variables, the two sample Wilcoxon rank-sum test for non-parametric continuous variables, and the Fisher test for categorical variables. A p < 0.100) excluding those which were found to be collinear by calculating variance inflation factors (VIF). However, there were not significant differences between the no residual and residual groups and logistic regression analysis was not required. Post-hoc analysis demonstrated that our study had 73% power to detect as statistically significant the observed differences of age at full enteral feeding between the groups.We planned to perform logistic regression analyses to assess the possible correlation between the primary outcome and variables that at univariate analysis were different between the groups (P = 0.320), were similar between the groups , full oral enteral feeding , and birth weight recovery  was lower while Z-scores of weight at discharge  were higher in infants in the selective GR group in comparison to infants in the routine GR group (Tables Age at full (150 mL/kg) enteral feeding  enteral feeding sooner. These results are in agreement with previous studies. Abiramalatha et al. meta-analysed two randomised controlled studies which enrolled 141 very low birth weight infants and found that routine monitoring of GRs increases the time needed to establish full enteral feeds, to regain birth weight, and the s duration of parenteral nutrition . These rOur study confirms that avoiding routine monitoring of GRs is not associated with an increase of incidence of NEC. A similar result was reported by several studies , 21, 22 We found that the time to regain birth weight and Z-scores of weight at discharge were significantly better in infants in the no routine residual group than in the control group, while Z-scores of length and head circumference were similar. These findings are in agreement with previous studies , 12, 13 The main limitation of this study is that it was a retrospective single center study based on a “before and after” design which cannot rule out the possibility of unmeasured confounding factors contributing to the results. However, during the study periods clinical practice at the center did not change and our findings were substantially in agreement with previous studies. These considerations, together with the similar demographic and clinical characteristics of the study groups, support the reliability of our results. Another limitation regards the size of our population which did not allow us to find statistical significance in the shortening of parental nutrition, stay in NICU and in hospital duration that we observed as a trend in the selective GR monitoring group in comparison with the routine GR monitoring group. Furthermore, although we have not observed significant changes in the onset of NEC, our study does not have sufficient power to definitively exclude the risk of its increase. However, despite these limitations, we believe our study adds useful contemporary data about implementing a new protocol of monitoring in term of its effects and safety in a NICU.In conclusion, we found that the selective monitoring of GRs in a cohort of extremely preterm infants was associated with a decrease of age at full enteral feeding and at birth weight recovery and with better Z-scores of weight at discharge in comparison with routine GR monitoring. The incidence of NEC did not increase although this finding, while in agreement with previous studies, should be confirmed in a larger population. The assessment of GRs is time consuming and devoid of beneficial effects. Thus, its current widespread application seems no longer justified according to literature evidence, while it seems reasonable to omit prefeed GRs monitoring in clinical practice.Additional file 1.


The outbreak of the COVID-19 pandemic caused great uncertainty about causes, treatment and mortality of the new virus. Constant updates of recommendations and restrictions from national authorities may have caused great concern for pregnant women. Reports suggested an increased number of pregnant women choosing to give birth at home, some even unassisted (‘freebirth’) due to concerns of transmission in hospital or reduction in birthplace options. During April and May 2020, we aimed to investigate i) the level of concern about coronavirus transmission in Danish pregnant women, ii) the level of concern related to changes in maternity services due to the pandemic, and iii) implications for choice of place of birth.n = 30,009) in April and May 2020.We conducted a nationwide cross-sectional online survey study, inviting all registered pregnant women in Denmark . Concerns of transmission during pregnancy and birth were considerable; 63% worried about getting severely ill whilst pregnant, and 55% worried that virus would be transmitted to their child. Thirtyeight percent worried about contracting the virus at the hospital. The most predominant concern related to changes in maternity services during the pandemic was restrictions on partners’ attendance at birth (81%). Especially nulliparous women were concerned about whether cancelled antenatal classes or fewer physical midwifery consultations would affect their ability to give birth or care for their child postpartum.. The proportion of women who considered a home birth was equivalent to pre-pandemic home birth rates in Denmark (3%). During the temporary discontinue of public home birth services, 18% of this group considered a home birth assisted by a private midwife (n = 125), and 6% considered a home birth with no midwifery assistance at all (n = 41).The response rate was 60% (Danish pregnant womens’ concerns about virus transmission to the unborn child and worries about contracting the virus during hospital appointments were considerable during the early pandemic. Home birth rates may not be affected by the pandemic, but restrictions in home birth services may impose decisions to freebirth for a small proportion of the population. During the early months of 2020, the world faced an outbreak of the previously unknown coronavirus disease COVID-19), which rapidly evolved into a global pandemic. At the pandemic onset, little was known about the virus and its effects on the pregnant woman, the fetus, and the newborn child 9, which . They haThe pandemic has created stress and anxiety among pregnant women in different parts of the world –6. RecenThe International Confederation of Midwives (ICM) has raised concerns regarding the human rights of women and their babies by the introduction of alternating protocols for management of pregnancy, birth, and postnatal care in response to the COVID-19 pandemic . In DenmWe conducted a national survey among Danish pregnant women (COVIDPregDK) in April and May 2020. The objective of this study was to investigate i) the level of concern about coronavirus transmission in Danish pregnant women, ii) the level of concerns related to changes in maternity services due to the pandemic, and iii) implications for their choice of place of birth during the pandemic.We conducted a nationwide cross-sectional study using survey data on all registered pregnant women  on April 24, 2020. We used the data to describe concerns regarding pregnancy and birth in relation to the COVID-19 pandemic.Denmark was one of the first countries to initiate a National lockdown with closed institutions and public workplaces on March 11, 2020 . All nonMaternity services in Denmark were considered as critical functions. Antenatal or outpatient appointments were continued or replaced with video consultations. Antenatal classes were cancelled or replaced with online classes or videos. The woman’s partner was not allowed to participate in ante- or postnatal appointments, including ultrasound scans, and he or she was only allowed in the labour ward if they had no symptoms of COVID-19. Home birth services were temporarily discontinued in four out of five regions.The Danish National Patient Registry is a nationwide hospital register which is used extensively for research. It contains information on all hospital contacts in Denmark and, due to the Danish tax-funded health care system, virtually all pregnancies and childbirths are registered , 16. ForWe constructed a questionnaire in March 2020 aimed at pregnant women during the early COVID-19 pandemic. It included questions on COVID-19 worries related to pregnancy and birth, worries related to experienced effects of changes in maternity services, and finally questions on considerations regarding the place of birth. These three dimensions are the focus of this study, and the items were developed specifically for this study. Due to the exceptional circumstances of the lockdown, the time frame for the development of these dimensions did not allow for piloting or testing for internal consistency. The questionnaire also covered demographics, general health, COVID-19 symptoms and testing, and mental health, including anxiety and stress. It can be seen in full in the baseline article of the COVIDPregDK study .From the COVIDPregDK survey, we retrieved background information on age and parity (0/≥1) as well as information on any positive COVID-19 tests in the woman’s household prior to the survey.Concerns about the transmission of COVID-19 during pregnancy and birth were addressed in items related to various potential transmission situations framed as: “To what extent are you worried about…..?” with the following five response categories: “To a great extent, to some extent, to a small extent, not at all, or don’t know”. Similarly, the items on concerns on changes in maternity services included questions on worries of not having antenatal healthcare visits, changes in settings, fewer possibilities in childbirth, including restrictions on the presence of a partner. These items held the same response categories as above.Finally, considerations on place of birth were addressed in a series of items on home birth. To give the women the possibility to reply as accurately as possible, the response categories for these items varied accordingly.During and after the development of the questionnaire, a panel of six pregnant women  filled out the questionnaire and gave their feedback, resulting in a clarification of questions and a more user-friendly layout.P-values < 0.05 were regarded as statistically significant.To characterize the study population, we used statistics presenting means with standard deviations on continuous data and distribution of frequencies for categorical data on demographics and baseline data. To illustrate the distribution of answers to each question, we tabulated each reply and presented them as plotted figures with information on numbers and percentages. We performed the descriptive analyses according to parity since answers were expected to differ between nulliparous (nullips) and multiparous women (multips) and tested for difference by chi2 tests. n = 52 and 35, respectively). To be noted, during most of the data collection period, the availability of tests in Denmark was limited and restricted to severe cases with symptoms of COVID-19 that required treatment.A total of 17,995 women participated in the survey . The response rate was 60%. The participating women had a mean age of 30 years, with a slight majority being multiparous (52%). For characeteristics  on study population, see Table p-values < 0.05 except for worries for infection due to hospital contacts, p-values 0.06).Figure p-values were statistically significant.Regarding concerns related to changes in maternity services, we observed a considerable difference between nulliparous and multiparous women Fig. . Fifty-fno , 3.5% replied yes (n = 659), 1% replied yes, but conditions related to my pregnancy has led to professional advice against home birth (n = 173), 3.3% had still not decided (n = 586), and 0.5% did not know (n = 92). In the group of women who opted for a home birth, only 26% were nulliparous, and significantly more had a medium or long education than the women opting for a hospital birth. For characeteristics  on study population according to place of birth preference, see Table All participants were asked whether they had planned a home birth prior to the pandemic, and 81.5% replied now n = 9. In the n = 651) agreed to. In this group, 254 women would now prefer giving birth at home instead of the hospital, and 397 would now prefer giving birth in a hospital instead of at home , 1% were undecided (n = 164). Of the 698 women who considered a home birth, 81% preferred to give birth at home because they felt most safe in their own surroundings, whilst 20% preferred a home birth because they felt less safe in a hospital. Half of the women considering home birth (n = 349) stated that avoiding infections in the hospital was a part of the reason for their decision, and only 16% specifically stated COVID-19 infection as a reason   nulliparous and 114 (22%) multiparous women considered giving birth at home despite the discontinued midwifery services due to COVID-19 restrictions, and 123 (18%) were undecided  participated. Concerns of transmission were considerable and related to getting severely ill and transmitting the virus to the unborn child. Just over one third worried that they would contract the virus during hospital appointments or while admitted to hospital (e.g. when giving birth). Concerns related to changes in maternity services during the pandemic were significant and even more among nulliparous than multiparous women. Nulliparous women were especially worried about whether the changed level of maternity services would affect their abilities to give birth and care for their child after birth. A predominant concern for all women was whether their partner would be allowed to attend the birth. In the subcohort of women planning to give birth at home, one in five considered a home birth assisted by a private midwife and a small proportion considered giving birth with no midwifery assistance at all. Feeling safe in own surroundings was a more prevalent reason for planning a home birth than fear of nosocomial infections.This is the first population-based study to investigate pregnant women’s concerns about pregnancy and birth during the first wave of the COVID-19 pandemic and lockdown measures in Denmark. This study has a registerbased inclusion of pregnant women and the Danish secure digital solution (e-boks) allowed contact and invitation to virtually all relevant potential participants. We consider this to be a strength compared to studies recruiting women via social media, but with a response rate of 60%, selection bias must also be considered in this study. We acknowledge that this study is purely descriptive and statistics are used accordingly. Our aim was to describe our study population on concerns related to the pandemic and pregnancy and implications for women’s choice of birth place. Due to the very large sample size, test for differences between nulli- and multiparous women, were mostly statistically significant, however the clinical relevance was regarded of little importance unless stated.At the time of our data collection, much was still unknown about the virus and its effects on both the pregnant woman, the fetus, and the newborn child , leavingAlthough a generally high level of concern about the consequences of the changed level of maternity services was found in this study, it was more pronounced in the group of nulliparous women. Childbearing, from conception until after the birth of a woman’s first child, is a major life event that can bring about many challenges for the woman and her family , 22. Conco-pilot, a voice of reason and an advocate who will speak up for their rights and wishes in case they are not able to make decisions themselves [The support of the partner during labour and childbirth seems to be of paramount importance as an encourager and to give the woman confidence in her ability to get through the labour . In thisemselves .n = 659) had planned to give birth at home before the pandemic, and 3% (n = 586) were undecided. However, the impact of this restriction was so distressing that a small group either considered or were undecided about giving birth at home regardless either assisted by a privately funded midwife or without midwifery assistance. This stresses that maternity services need to provide support for all pregnant women, regardless of their reasons for birthplace preferences during a pandemic to prevent them from withdrawing from maternity services.Another restriction from the authorities during the first lockdown in March, April and May 2020 was the temporary discontinuation of home birth services in four out of five regions in Denmark. This measure affected a smaller proportion of the participants since 4% (Rapid-response articles have suggested that the COVID-19 pandemic will lead to an increase in births at home or in smaller units outside the hospital , 10, 25.From a global perspective, the pandemic has different consequences in different healthcare settings, and these Danish findings may not be transferable to low and middle-income countries. However, pregnant women, infants and new mothers are decidedly vulnerable in times of disasters and crisis in all parts of the world. According to WHO, all pregnant women and their newborns, including those with confirmed or suspected COVID-19 infections, have the right to high quality care before, during and after childbirth, including mental health care. This includes being treated with respect and dignity, having a companion of choice present during delivery, clear communication by maternity staff, appropriate pain relief strategies, mobility in labour and birth position of choice . ICM recIf COVID-19 is suspected or confirmed, health workers should take all appropriate precautions to reduce risks of infection to themselves and others, including hand hygiene, and appropriate use of protective clothing like gloves, gown and medical mask.Concerns of transmission and concerns related to changes in maternity services during the pandemic, including restrictions on partners’ attendance at birth, were considerable, especially for nulliparous women in the early COVID-19 pandemic. The proportion of women who considered a home birth during the first lockdown in March and April 2020 was equivalent to the present home birth rate in Denmark. However, despite temporary discontinue of home birth services, a small proportion considered a home birth either assisted by a privately funded midwife or with no midwifery assistance at all.


Preterm birth (birth before 37 weeks gestation) is the leading cause of neonatal mortality, is associated with long-term disability in survivors, and carries a substantial economic burden to healthcare and social services . There iPLOS Medicine, Landman and colleagues report on a randomised controlled trial designed to assess the effectiveness of low-dose aspirin in the prevention of preterm birth in women at high risk of preterm birth [There has been little data from primary trials to guide practice in this area. In an accompanying research study in rm birth . Women wThe sample size calculation for the APRIL trial was based on a potential 35% relative reduction in the rate of preterm birth , from a background rate of 36%. This background rate was derived from a trial of progesterone to prevent preterm birth which recruited participants from the United States in the late 1990s, but is higher than that cited in more recent literature, especially if other preterm birth treatments are administered . In the The feasibility of carrying out a very large trial in the population of women at risk of preterm birth in the future is uncertain, given that there is already high use of aspirin prophylaxis for preeclampsia in many settings. Although an indication for aspirin was an exclusion criterion for the APRIL trial, the baseline demographics suggest that women were included who would have had aspirin prescribed according to current clinical guidelines in many countries. For example, women with hypertension, kidney disease, systemic lupus erythematosus, or diabetes would be recommended aspirin under the US , the UniOne approach for future research would be to identify groups of women at risk of specific phenotypes of preterm birth in whom aspirin is most effective. Prespecified subgroup analysis in the APRIL trial  hinted tA key issue to address in future research is the dose of aspirin that may be most effective. Even for preeclampsia prophylaxis, the optimal dose is uncertain, with ranges from 75 mg to 160 mg daily used . AlthougThe APRIL trial illustrates the need for better understanding of the mechanisms underlying preterm birth to enable development of appropriate and targeted treatments . Until t


Objective: Prader-Willi syndrome (PWS) is a rare genetic syndrome with a wide spectrum of clinical features in early life. Late diagnoses are still present. We characterized the perinatal and neonatal features of PWS, compared them with those of healthy newborns and assessed the prenatal and neonatal differences between the genetic subtypes. Design: A cohort study in children with PWS. The prevalence of variables was compared with healthy infants (PLUTO cohort) and to population statistics from literature. Patients: 244 infants with PWS and 365 healthy infants. Measurements: Data on prenatal and neonatal variables in both cohorts. Population statistics were collected through an extensive literature search. Results: A higher prevalence of maternal age >35 years was found in PWS compared to healthy infants and population statistics, and the highest maternal age was found in the mUPD group. Higher prevalence of polyhydramnios, caesarean section, labour induction and breech presentation, and lower birth weight SDS was found in PWS compared to healthy infants. High prevalences of decreased fetal movements (78.5%), hypotonia (100%), cryptorchism (95.9%) and poor sucking/tube feeding (93.9%) were found in PWS. Conclusions: This study presents an overview of prenatal and neonatal variables in infants with PWS compared to healthy infants. Our findings may increase clinical awareness of the early perinatal signs of PWS by obstetricians, neonatologists and all those involved in infant care, enabling early diagnosis and start of multidisciplinary treatment. Prader-Willi syndrome (PWS) is a rare and complex genetic syndrome characterized by hypotonia, infantile feeding difficulties and, later on, hyperphagia, which will lead to obesity when uncontrolled, combined with many comorbidities such as short stature, typical facial dysmorphism, psychomotor delay, hypogonadism, behavioral abnormalities and cognitive impairment ,2. HypotPWS is caused by a lack of expression of the 15q11-q13 region on the paternally inherited chromosome, caused by a deletion (65–75%), maternal uniparental disomy (mUPD) (20–30%), imprinting center defect (ICD) (1–3%), or a translocation (<1%) [Despite the availability of advanced genetic testing that makes it possible to diagnose children in the first few months of life, delayed diagnosis of PWS is still reported ,7. This Although perinatal and neonatal characteristics in PWS have been reported ,20,21,22Patients who were included in the Dutch PWS Cohort Study since the start in 2002  until JuThe control group consisted of healthy term-born infants, participating in the Sophia Pluto study (PLUTO cohort), a birth cohort of healthy term-born infants, aiming to provide detailed and longitudinal data on growth and body composition trajectories from birth to age five years . In thisAll patients were examined during their first visit at the PWS Reference center by the Dutch PWS-team, consisting of a pediatric endocrinologist, a pediatrician, three physicians with PWS experience, a dietician, a psychologist and two nurses. Most data were available from medical records, and both parents and physicians completed standard questionnaires about maternal and perinatal characteristics. The healthy infants were included and examined before the age of 28 days. The Dutch PWS Cohort study  and Sophia Pluto Study  were approved by the Medical Ethics Committee of the Erasmus University Medical Center. Both studies were conducted according to the guidelines of the Declaration of Helsinki II. Written informed consent was obtained from parents and patients older than 12 years. Assent was obtained from patients younger than 12 years.Medically assisted reproduction was defined as treatment with intrauterine insemination (IUI), in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Parents were asked if their child required breathing support after birth . Birth weight, -length and -head circumference were converted into Standard Deviation Scores (SDS) with Growth Analyser RCT 4.1, based on Dutch References . Small fp-values of < 0.05 were considered statistically significant.Statistical analyses were performed using IBM SPSS Statistics 25. Categorical variables were reported using frequencies and continuous variables and were expressed as median ± interquartile range (IQR), as not all variables had a normal distribution. Comparison of variables between the PWS cohort and PLUTO cohort was performed by Mann–Whitney U tests. Categorical data were compared by Chi-Square tests. Differences between the three genetic subtypes were analyzed by Kruskall–Wallis tests. Data of the PWS cohort were compared to the general population  using the Z-test for proportion  or the One-Sample Wilcoxon Signed Rank Test (continuous variables). When a range of prevalence was given, the average value was used for statistical analyses. This study consisted of 244 patients with PWS, including 117 patients (50.0%) with a deletion of the paternal copy of 15q11-13, 106 (43.4%) with mUPD and 10 patients (4.1%) with ICD. In 11 patients (4.5%) the genetic subtype was unknown. The median (IQR) age at the first visit to the Dutch PWS Reference center was 1.23  years. A group of 365 healthy, term-born infants (PLUTO cohort) was used as a control group. There was no significant difference in sex between the two cohorts or between the genetic subtypes in the PWS study population .p = 0.078), and the prevalence of high maternal age at birth (>35 years) was higher in the PWS cohort (p = 0.028). The median paternal age did not differ  and oligohydramnios (7.7% versus 0.3%) were higher in PWS than in the PLUTO cohort. There was no significant difference in miscarriage in maternal history or in use of medically assisted reproduction between the cohorts.Maternal age at delivery tended to be higher in the PWS cohort (median (IQR) 33.0 (30.0–37.0 years) compared to the PLUTO cohort (32.0 (29.0–36.0 years) (t differ . Maternap <0.001), but the prevalence of breech presentation and induced labor was significantly higher in the PWS .Mode of delivery differed between the cohorts, with a higher caesarean section rate (46.3%) in PWS than in the PLUTO cohort (29.0%), but no difference in the ratio of type 1 (elective) versus type 2 (emergency) caesarean sections . A lowerp = 0.076)). Infants with PWS were more often SGA compared to the PLUTO cohort (21.1% versus 2.5% (p <0.001)).Birth weight and birth length SDS were significantly lower in the PWS compared to the PLUTO cohort . Head cip < 0.0001), resp. (p < 0.001). Paternal age was higher in PWS, compared to the (Dutch) general population (p < 0.001). Pregnancy complications occurred more often in PWS, specifically pregnancy hypertension/pre-eclampsia (p < 0.001), premature rupture of membranes (p <0.001) and both polyhydramnios (p < 0.001) and oligohydramnios (p < 0.001) [p = 0.088) [Maternal age was higher in the PWS cohort in comparison with Dutch population data, 33.0 vs. 30.2 years  (p < 0.0), resp. . The pre< 0.001) . Previou= 0.088) .p <0.001), without difference in the type of caesarean section. Breech presentation was more common in PWS as well.Both preterm and late/post-term births occurred more often in PWS compared to the (Dutch) general population . The caeIn the mUPD group, a higher median maternal age, a higher prevalence of high maternal age at birth (>35 years), and a higher paternal age were found, compared to the other genetic subtypes . The difp = 0.014).No differences were found between the genetic subtypes regarding birth weight, length or head circumference SDS . The prep < 0.001)).Apgar scores did not differ between the genetic subtypes . The preThis study highlights the prenatal and neonatal features in a large cohort of 244 Dutch patients with PWS. We found a higher prevalence of high maternal age at birth (>35 years) and polyhydramnios in the PWS cohort compared to the PLUTO cohort. Compared with general population statistics, pregnancy complications also occurred significantly more often in PWS. Maternal and paternal age were found to be higher in the mUPD group compared to the two other genetic subtypes. Birth weight and length SDS were lower in PWS compared to the PLUTO cohort. Additionally, the prevalence of small for gestational age (SGA) was higher in PWS and particularly in the mUPD group. With regard to delivery characteristics, a higher caesarean section rate, higher prevalence of induction of labor and breech presentation were found in PWS compared to the PLUTO cohort. The neonatal variables were not different between the genetic subtypes, except for the age at genetic diagnosis, which was significantly higher in the mUPD and ICD groups. In addition, we listed the most prevalent perinatal and neonatal characteristics of PWS with the aim to increase the clinical awareness of PWS symptoms and we present a flowchart for genetic testing for PWS in a newborn.In the PWS cohort, a higher prevalence of mothers being >35 years was found. The highest maternal age was found in the mUPD group, which is in line with a previous study . AdvanceComplications were more common during PWS pregnancies, compared to Dutch population statistics, but not compared with the PLUTO cohort. In the PLUTO study, most children were included at maternity wards. Since home deliveries are relatively common in the Netherlands, we expected a higher prevalence of complications during pregnancy and labor in case of hospital deliveries, and, therefore, compared also with Dutch population statistics. Polyhydramnios and a history of miscarriage have been reported as a feature of PWS ,19,44. HThe prevalence of medically assisted reproduction tended to be higher in PWS compared with the general population. We expected this association to be attributed to increased risk of UPD in pregnancies that resulted from medically assisted reproduction, but there was no difference in the prevalence of medically assisted reproduction between the genetic subtypes. In the literature, an increased risk of imprinting disorders after IVF/ICSI has been described, especially for Angelman and Beckwith-Wiedemann syndrome ,47,48. BNotably, birth weight SDS was significantly lower in PWS, while head circumference SDS at birth was not affected. The higher prevalence of SGA birth in the mUPD group has not been reported earlier, although one study found a tendency towards a lower birth weight SDS in the mUPD group . In an IThe PWS cohort had more preterm (<37 weeks) and late/post-term births >41 weeks) compared to the general population. The higher rate of preterm births may be explained by the higher prevalence of pregnancy complications, such as decreased fetal movement and preterm rupture of membranes, which increase the risk of induced and premature labor. Post-term delivery may be explained by fetal hypotonia in PWS, which makes spontaneous delivery more difficult. We found no difference in gestational age between the genetic subtypes, which is in line with another recent study . However weeks coInduced labor was more prevalent in PWS than in healthy infants and in the general population. Dudley et al. hypothesized that lower oxytocin levels in PWS infants might be the cause of the higher prevalence of induced labor , as oxytNext to hypotonia, several neonatal features, such as cryptorchidism and feeding difficulty requiring tube feeding were very common in PWS infants. The prevalence of cryptorchidism was similar as reported in other studies ,19,45,55The age at genetic diagnosis was significantly higher in the mUPD and the ICD groups, which is in line with a recent study, describing an earlier diagnosis in patients with a deletion . As an eSince the development of methylation analysis, the diagnosis of PWS can be made with 100% certainty. Diagnosis is nowadays increasingly suspected in the first weeks of life, with a genetic diagnosis a few weeks later. However, in many countries and also in our PWS cohort, delayed diagnoses are present when symptoms are not recognized or milder than expected with PWS . No single prenatal or neonatal finding is specific for PWS, but PWS should be considered when a newborn or infant has hypotonia in combination with a poor suck and tube feeding, particularly in the case of severely decreased fetal movements. Next to these core features, there are supportive clinical features, such as cryptorchidism in boys, polyhydramnios, breech presentation, induction of labor, caesarean section, born SGA, breathing problems and prolonged hospitalization (>20 days). In literature, hypotonia is often described as central or peripheral ,58, but Our study has several strengths, such as the large number of patients with PWS. As the Dutch PWS Cohort study has been following patients since 2002, it was possible to include many young PWS patients over the years. Our study has more patients with mUPD compared to other studies ,6,18,44,Most of the characteristics were in medical records or asked and recorded by the PWS team during the first visit at the PWS Reference center when the infants had a median age of 1.23 years. The questions about the perinatal period were, however, prone to some recall bias. Another limitation is the potential bias of the PLUTO study, which included most infants at maternity wards. Since home deliveries are relatively common in the Netherlands, the prevalence of complications during pregnancy or labor might be higher in hospital deliveries, which may result in bias regarding the pregnancy complications and labor characteristics in the PLUTO cohort. We, therefore, added the comparison with the general population statistics.In conclusion, our study presents an overview of prenatal and neonatal variables in infants with PWS compared to healthy infants. Our findings show that suspicion of PWS can be raised prenatally and postnatally and that the diagnosis can be made within the first weeks of life. When the prenatal PWS phenotype is recognized by obstetricians, this can prepare both obstetricians and families. The recognition of early symptoms in newborns by clinicians and other health care workers is important for early diagnosis and the start of multidisciplinary treatment, which can lead to better outcomes in later life. Our findings may increase clinical awareness of the early perinatal signs of PWS.


Poor birth outcomes are an important global public health problem. Social assistance programs that provide cash or in-kind transfers, such as food or vouchers, hold potential to improve birth outcomes but the evidence on their effectiveness has not been reviewed.We systematically reviewed studies that used experimental or quasi-experimental methods to evaluate the impacts of social assistance programs on outcomes in low- and middle-income countries.The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to assess the certainty of the evidence for birth weight and neonatal mortality (most common outcomes reported). We summarized the evidence on hypothesized nutrition and health pathways of impact.P < 0.05) effects ranging from 31 to 578 g. Out of 3 studies that assessed neonatal mortality impacts, 2 found significant effects ranging from 0.6 to 3.1 deaths/1000 live births. The certainty of the evidence for both outcomes was rated as very low due to several methodological limitations. In terms of potential pathways, some studies documented positive effects on maternal diet, antenatal care (ANC) utilization, and delivery in a health facility.We included 6 evaluations of 4 different cash transfer programs and 1 evaluation of a community-based participatory learning and action program that provided food and cash transfers. The 4 studies that assessed birth weight impacts found significant (Better-designed evaluations are needed to strengthen the evidence base on these programs. Evaluation studies should elucidate underlying mechanisms of impact by including outcomes related to maternal diet, ANC seeking, use of skilled delivery, and women's empowerment in nutrition and health domains. Studies should also assess potential unintended negative consequences of social assistance, such as reduced birth spacing and excess pregnancy weight gain. In 2012, an estimated 23.3 million infants or 19.3% of live births were born small-for-gestational-age in low- and middle-income countries . The gloMaternal undernutrition is an important contributor to adverse birth outcomes . Both miProven approaches to improving diets and nutrient intakes during pregnancy include nutrition counseling, iron/folic acid or multiple micronutrient supplements, and balanced energy and protein supplementation .In 2016, the WHO issued new recommendations on antenatal care (ANC), which included a set of nutrition interventions focused on improving diets and nutrient intake during pregnancy . In foodThe WHO recommendation implies a research agenda aimed at understanding whether social assistance programs, which provide transfers—either cash or in-kind—to poor households, offer a promising platform to leverage improvements in birth outcomes. These programs are becoming increasingly popular in low- and middle-income countries, especially in food-insecure areas. Their scale and targeting to vulnerable households make them promising for reaching nutritionally at-risk populations. Moreover, there are a number of plausible nutrition and health pathways by which social assistance programs could improve birth outcomes. To develop a research agenda to rigorously assess the effectiveness of such approaches in improving birth outcomes, it is useful to first take stock of what existing evidence shows about program impacts and pathways. Thus, the first objective of this paper was to systematically review the evidence on the impacts of social assistance programs, measured by experimental and quasi-experimental methods, on birth outcomes in low- and middle-income countries. The second objective was to explore evidence on nutrition, health, and other pathways of impact.Cash and food transfers can improve household food availability and, consequently, women's diet and nutritional status . The proThe impact of social assistance programs on birth outcomes could also be negative. Transfer programs that are conditional on being pregnant or that provide per-child benefits may create an incentive for women to become pregnant again (or sooner), though most studies find only small effects or no effects . ShorterThis systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement . The revThe review was limited to empirical studies that used experimental or quasi-experimental designs to evaluate the impact of social assistance programs on birth outcomes in middle- or low-income countries. Social assistance programs were defined broadly and included programs providing cash or in-kind transfers such as food or vouchers. Interventions that only provided dietary supplements or fortified products such as lipid-based nutrient supplements targeted to pregnant women were excluded from the review. Studies were required to assess program impacts on at least 1 of the following outcomes: birth weight, low birth weight (defined as weight <2500 g), being small for gestational age, and neonatal mortality .The review was limited to articles published in English in or after 2000. Studies had to be original research articles. We thus excluded editorials, commentaries, and similar non–primary research articles. We further excluded studies without a comparison group.Supplemental Methods.Details on the search strategy are provided in the We first reviewed the titles of all identified articles to exclude studies that were clearly outside the scope of the review. We subsequently read the abstracts to exclude papers not meeting the criteria for study scope and study type. Finally, we read the full text to exclude ineligible papers missed in the first 2 steps. The included papers were summarized in tabulated form using the following categories: country, intervention (including the eligibility criteria), sample characteristics , evaluation design and analytic method , and results by outcome. Authors of included studies were contacted to provide additional details on their analyses.Due to the small number of studies identified and the heterogeneity in the evaluation designs used, no quantitative synthesis of findings was conducted.Two independent reviewers (JLL and BK) used GRADE  to assess the certainty of the evidence for birth weight and neonatal mortality, the 2 outcomes that were reported by at least 3 studies. As opposed to a study-level assessment, GRADE is used to reflect the extent of confidence in the outcome-level effect estimates, that is, considering the entire body of evidence . Any disThe review focuses on birth outcomes as defined above. We also reported on outcomes that help understand the nutrition and other pathways of impact, to the extent that these were reported in the included studies. Our critical review  was limited, however, to the birth outcomes. The principal summary measures were differences in means and differences in probability.P values if reported by the authors. When authors did not report the CI, we provide the SE. If exact P values were not reported, we state whether they were smaller than 0.05 or 0.10.Impact estimates are reported with CIs and exact Our initial search yielded a total of 5489 articles, of which 5223 and 160 were removed after screening the title and abstract, respectively . Since 2The studies included 6 evaluations of 4 different cash transfer programs implemented in Mexico (2 studies), Colombia (1 study), India (2 studies), and Uruguay (1 study) and 1 evaluation of a community-based participatory learning and action (PLA) program in Nepal . The proSupplemental Results.Importantly, improving birth outcomes was the primary objective of only 2 of the evaluated programs . Mexico's program included specific intervention components that could improve birth outcomes: the requirement to attend ANC and the provision of a micronutrient-fortified supplement for pregnant women. The programs in Colombia and Uruguay did not include any intervention component aimed specifically at improving birth outcomes. The Uruguayan program conditions, which included ANC attendance during pregnancy, were not enforced. Details on each of the interventions are provided in the All studies used experimental or quasi-experimental evaluation designs . For theIn Mexico, Barber and Gertler , 37 usedQuasi-experimental designs were also used in the 2 studies that estimated the impacts of India's Janani Suraksha Yoijana (JSY) program , 40. TheA quasi-experimental design was also used to evaluate the Familias en Acción program in Colombia . All munThe most commonly reported birth outcomes were birth weight (4 studies), low birth weight (3 studies), and neonatal mortality  and delivery at a health facility (4 studies). No outcomes related to nutrition and health pathways were assessed in the studies.P = 0.0143) was found; the point estimate of the impact in the PLA-plus-cash arm (50 g) was not significantly different from 0, likely because of the considerable loss in statistical power following severe attrition due to the problems in the field team (P = 0.0397) and the PLA-plus-food arm , but not in the PLA-only arm. The intervention had no impact on the prevalence of low birth weight.The 4 studies assessing birth weight found a consistent, positive impact on this outcome. In Nepal, the effect on birth weight (measured within 72 h after birth) was limited to the PLA-plus-food arm, in which a 78 g impact  to 127 g ; the program reduced the prevalence of low birth weight by an estimated 4.4 , to 4.6 percentage points . With a low-birth-weight prevalence in the control group of 10.3%, this suggests that the program almost halved the prevalence of low birth weight. In Colombia, the impact of the Familias en Acción program on birth weight was limited to urban areas (P < 0.05) to be biologically implausible since women in the study were not severely undernourished prior to the intervention. PANES in Uruguay was found to have a positive effect on birth weight of 31 g  (P < 0.01), to 2.5 percentage points , equivalent to a 20% reduction of the preprogram prevalence. Additional analyses showed that the program's impact on birth weight was larger for premature children, children of unmarried mothers, and teen mothers. Across the 4 studies, the overall certainty of evidence on birth weight and low birth weight was rated as very low  . It reduvery low .P < 0.05) to 4.1  deaths/1000 pregnancies in 2 of the 3 model specifications (the difference-in-difference model did not demonstrate a significant program impact), equivalent to a 9% to 10% reduction. The estimated reduction in neonatal mortality (significant in the same 2 model specifications) was 2.3  to 2.4  deaths/1000 live births, equivalent to a 7% reduction. Interestingly, the largest mortality reductions were found in the non-high-focus states, which were defined as having low in-facility birth coverage (P < 0.1), a 10% reduction compared to districts with a coverage level below 10%. When covariates were added to the model, however, the point estimates were no longer significant. The effect on 1-d mortality was a decrease of 2 deaths per 1000 live births , equivalent to a 13% reduction. This estimate did not change when covariates were added to the model. No impact was found at coverage levels lower than 50%.Evidence on neonatal mortality was found in India and Mexico , 39, 40.coverage . In contP < 0.1) to –1.32 (P < 0.1) deaths/1000 live births, depending on the model specification (P < 0.05), equivalent to a 19% reduction. The analysis of effect modifications by municipality characteristics resulted in inconsistent findings. The program impact was higher in municipalities with fewer households with electricity or in those with larger households (P for interaction < 0.01). The impact on mortality was smaller, however, in municipalities where fewer households had access to piped water (P for interaction < 0.05), in those with more households with dirt floors (P < 0.01), and in those with a larger proportion of the population working in the agricultural sector (P < 0.01). The certainty of the evidence for neonatal mortality was graded as very low  and 0.06 , respectively.No impact was found on gestational length or prematurity in the Nepalese and Uruguayan studies where these outcomes were measured. No impact was found in Nepal on length or head circumference measured within 10 d after birth. Even though listed in the methods section of this study, no statistical analysis on stillbirths was reported. In Uruguay, the impacts on the 1- and 5-min Apgar scores were 0.09 . The effect on the number of eating occasions per day in this arm was +0.3 . Barber and Gertler ], delivery in a public health facility increased by 11 pp , and health worker–attended deliveries increased by 5.6 pp .The 2 evaluations of India's JSY program found mixed results on ANC care seeking: Lim et al.  found a P = 0.0344). No effect on place of delivery was found in the PLA or PLA-plus-cash arms.In Nepal, where a significant effect on birth weight measured within 10 d was found in the PLA-plus-cash and PLA-plus-food arms, women in the PLA-plus-food arm were significantly more likely compared to women in the control arm to deliver at a health institution .Barber and Gertler  found noWe reviewed the literature on the impacts of social assistance programs on birth outcomes in low- and middle-income countries. The 4 studies that assessed birth weight found positive impacts on this outcome , 41, 42,In spite of the relatively low certainty of the evidence, the size of the estimated impacts on birth weight and neonatal mortality is clinically relevant. A meta-analysis of energy and protein supplementation interventions during pregnancy found an increase in birth weight of 41 g . MultiplEvidence on the nutritional pathways of impact in the reviewed studies was limited. Only 1 of the studies, the evaluation of the Nepalese intervention , assesseEvidence on health pathways was mixed. JSY in India increased the proportion of women with at least 3 ANC visits even though the program did not promote the use of ANC , 40. MexWhat are the implications of our findings for policy and research? Even though the quality of the reviewed studies varied, the evidence suggests that social assistance programs can improve birth outcomes. This conclusion is supported by other evidence on their effectiveness. Cash transfer programs have been demonstrated to be an effective policy tool to reduce poverty, improve household food security, and increase spending on nutrient-rich foods; increase health care–seeking behavior, especially when health visits are a program requirement; have been shown to improve psychosocial health and to reduce domestic violence by a male partner; and may increase women's social capital and decision-making power , 46, 47.Following the WHO recommendation to expand research on the effectiveness of cash transfers and related approaches for improving birth outcomes, and given that existing evidence is promising but has very low certainty, carefully designed impact evaluations are needed to quantify the effects of social assistance programs on birth outcomes. Quasi-experimental studies are more feasible than randomized trials for mortality outcomes, since the detection of a meaningful mortality effect requires a very large sample size. This makes sufficiently powered randomized mortality trials prohibitively expensive to conduct, especially since social assistance interventions are difficult to randomize at the individual level; cluster randomization further increases sample size requirements. However, the use of randomized designs to evaluate the impacts of social assistance programs on other birth outcomes, such as birth weight, preterm delivery, and being small for gestational age, is achievable and would strengthen the evidence base. Even though the authors of the quasi-experimental designs included in this review used a variety of methods to reduce selection bias, the possibility of this bias affecting the results cannot be excluded (see last column in Evaluation studies should also elucidate the underlying mechanisms of impact to confirm the plausibility of findings and to adapt programs and increase their effectiveness. Since micro- and macronutrient deficiencies are important determinants of poor birth outcomes, assessing the impact of programs on dietary adequacy during pregnancy is important. Evaluations should also measure the impacts on ANC seeking, the quality of care women receive, and women's empowerment in nutrition and health domains.A number of other considerations would allow evidence to better inform policies and programs. Evaluation studies need to be conducted on a variety of programs in different settings to understand how intervention characteristics and contexts affect the sizes of the impacts on birth outcomes. Studies could be designed to better understand the differential effects of including pregnancy-specific behavior change communication and counseling and of using social protection programs to distribute special micronutrient-fortified foods and micronutrient supplements. Impact studies should also assess potential unintended negative consequences on outcomes, such as a decline in service quality of ANC, reduced pregnancy spacing, and excess pregnancy weight gain and subsequent weight retention during the postpartum period, as recently shown in Guatemala . Finallynxab292_Supplemental_FileClick here for additional data file.