This study extends Thaddeus and Maine’s (1994) “three delays” framework to model the interrelated barriers to maternal health care and birth registration. We focus on stateless persons and irregular migrants, populations that are especially at risk of being “left behind” in United Nations member states’ efforts to “provide legal identity to all” as part of the 2030 Sustainable Development Agenda. Drawing on qualitative fieldwork conducted in Sabah, Malaysia, we model delays in accessing maternal health care and birth registration as an integrated, cyclical process. We identify the political and legal barriers that stateless or migrant families confront while deciding to make institutional contact (Phase I), identifying and reaching health or registering institutions (Phase II), and receiving adequate and appropriate treatment (Phase III). We find that exclusion from one system raises the risk of exclusion from the other, resulting in a range of negative consequences, including increased health risks, governments’ impaired ability to monitor population health, and the perpetuation of intergenerational cycles of legal exclusion. In 2016, the United Nations made it a target “to provide legal identity to all, including birth registration” by 2030 as part of its Sustainable Development Goals (SDG) agenda, which succeeds the Millennium Development Goals of 1990–2015. In many respects, the achievement of universal birth registration is key to actualizing the SDGs’ pledge to “leave no one behind.” For one, the SDGs explicitly prioritize birth registration, because it provides individuals with their first—and often their most fundamental—form of legal identity, defined herein as the recognition of one’s personhood before the law , using Sabah, Malaysia, as a case study. A stateless person is defined by the 1954 Convention Relating to the Status of Stateless Persons as someone “who is not considered as a national by any State under the operation of its law.” We use the term “irregular migrants” to refer to people who engage in movement across an international border outside of the legal frameworks of their sending, transit, or receiving countries . Having undergone rapid economic development since the 1970s, Malaysia has made significant advances in improving its population health. For example, Malaysia’s reported infant mortality rate in 2019 was 7.2 infant deaths per 1000 live births, down from 67.2 in 1960 . This 2019 estimate is almost half that of the average for upper middle-income countries (11.6) and nearly five times as low as the global average (29.4) . The easternmost state of Sabah, where the majority of this research was conducted, has the highest ratio of citizens to non-citizens: nearly 1–3 , with the non-citizen population composed predominantly of persons of Indonesian and Filipino descent. These figures, however, may not take into account the significant yet unknown number of LMPs—stateless persons, irregular migrants, and their descendants—residing in the country who not only are left unaccounted for in official statistics but also are potentially deprived of a legal identity. Statelessness is a “homegrown” problem in Malaysia in that it is not only experienced by migrants and refugees, but also by several categories of people born and raised in Malaysia Liew, . One majProjek/Project IC).Under-registration in Sabah is more than a problem of lack of resources or technical capacity; it is intimately tied to questions of national identity and belonging Cheong, . LocatedExisting research on the intersections between health and registration status in Malaysia, and in particular Sabah, is scant. In their review article, Lasimbang et al.  lamentedBirths and Deaths Registration Act 1957 (Revised 1983), which mandates that “the birth of every child born in Malaysia shall be registered.”Registration of Births and Deaths Ordinance of 1951, which also makes no distinction as to the rights and obligations to register the births of citizens versus non-citizens. Civil registration and identity documentation matters in Malaysia are overseen by the National Registration Department , which was established in 1948 under the Ministry of Home Affairs and which implements the administrative procedures for registering births in Peninsular Malaysia, Sabah, and Sarawak.Civil registration in Peninsular Malaysia is governed by the In Malaysia, the onus for registering a birth is solely demand-driven, meaning that it is up to the parent, legal guardian, or “person having knowledge of the birth” to approach a National Registration Department office when a child is born. A successful registration of birth is dependent not only on whether an applicant reports its occurrence at a National Registration Department office, but also on the provision of necessary supporting documentation. In Sabah, a “normal registration of birth,” which occurs within 14 days of birth,Sabah Registration of Births and Deaths Ordinance of 1951.5The two forms issued by the National Registration Department at the time of registration are Form A and Form N1. Form A is the Citizenship Application Form , which is issued in accordance with the Federal Constitution Articles 15(1), 16, and 16A.Applicants are also required to produce forms that are issued by formal healthcare providers. These include the confirmation of birth form from the hospital, issued by the doctor, or certification of home birth from the midwife who attended the birth. The confirmation of birth contains information about the date and time of birth, the child’s weight and height, sex, method of delivery, and details about the doctor or midwife. Additionally required is a prenatal card : also known as a maternal examination book, which is issued by both public and private health facilities in Malaysia, this card tracks information about both mother and baby throughout the pregnancy stage. Finally, the applicant must also furnish the child’s health and immunization card, which contains information about the date of immunizations received, provided by the health worker who administered the immunizations.Documents are required from both biological parents. If the parents are Malaysian citizens, they must produce their MyKads, the national identity card that is compulsory for all Malaysian adult citizens to hold. Non-citizen parents are otherwise asked to provide their valid passports and entry permits. They are also required to provide a marriage certificate, divorce certificate, or death certificate(s) to determine the legitimacy of the child.The successful registration of a birth is, therefore, dependent on the acquisition of a number of documentary prerequisites. The complete set of medical documents can be obtained only through regular and sustained contact with a recognized healthcare provider throughout the prenatal and postnatal period, and not only during the event of birth itself. Furthermore, despite the legal mandate to register every child born within Malaysia, non-citizens are required to furnish their passports and entry permits, which effectively renders parents’ authorized status a prerequisite for the child’s recognition of birth. The National Registration Department’s complex and strict administrative requirements for registering a child’s birth create several opportunities for non-registration to occur, with non-citizens and LMPs being at a pronounced disadvantage.This study is based on ethnographic observations and 105 household interviews conducted with LMPs who faced challenges applying for vital documents and citizenship. This included undocumented migrants, asylum seekers, as well as undocumented and/or stateless persons who were born in Malaysia but were denied citizenship and/or the documentation to prove their claims. Interviews were conducted using an interviewing instrument that we call a “document inventory.” A document inventory is a qualitative, semi-structured interview framework that prompts families to take stock of the material evidence they possess to substantiate their legal identities and existence. We explored how families’ lives were shaped by documents over the course of a semi-structured interview about the household’s migration histories, everyday experiences living in Malaysia, the limitations and challenges they face, and the nature and frequency of their interaction with government institutions ; documentation ; and experiences and attitudes with regard to citizenship, migration, legal status, and residence.6Before proceeding with a discussion of our findings, we provide a brief overview of the demographic characteristics of the sample under study. Here, we report the characteristics of mothers and their children, given this study’s focus on maternal health. Of the 105 households captured during our fieldwork, 87 contained women who had at least 1 child, and 5 contained women who were pregnant at the time of the first interview.Based on the thematic coding of our qualitative data, we propose an integrated three delays framework that synthesizes and extends upon Thaddeus and Maine  and alsoBy transposing the three delays framework to the study of civil registration access in Indonesia, Bennouna et al.  demonstrParticularly instructive was Bennouna et al.’s  observatIn this study, we heed such recommendations about the importance of contact with healthcare institutions as a determinant of birth registration by explicitly modeling access to maternal health care and birth registration as cyclical co-determinants of one another, using the case of LMPs in Sabah, Malaysia. We venture that improving access to health care and improving governments’ ability to monitor population health via expanding civil registration coverage are mutually constitutive goals: Incomplete civil registration systems make it difficult to produce accurate vital statistics and population health indicators, such as infant and maternal mortality. Without vital documents, such as birth certificates, individuals, may face challenges establishing a legal identity, without which it may become difficult to regularize one’s status or even claim a nationality. The deprivation of legal identity is associated with an inability to enjoy its associated rights and benefits, including health care. Exclusion from healthcare systems raises the risk of mortality and morbidity, as well as the probability that such events play out beyond the knowledge of governing bodies. Out-of-system pregnancies and births increase infants’ risk of going unregistered, which can perpetuate an intergenerational cycle of exclusion Fig. .Fig. 2ThOur extension of the three delays framework brings to light previously undertheorized causes of delays to accessing both maternal health care and birth registration: those stemming from legal and political factors. Focusing on the experiences of LMPs in the Malaysian context compels us to avoid taking for granted the notion that access to basic rights, such as healthcare and identity documentation, are allocated on the basis of legal status. While Thaddeus and Maine  explicitMore recent research about maternal healthcare access, much of which is guided by the three delays approach, also privileges social, cultural, and economic barriers . Reliance on traditional midwives during both pregnancy and birth was a common strategy for women seeking to avoid costly institutionalized care completely. While bidan kampung, who often were elderly women from the coethnic community, played important and respected roles, they tended to lack professional training and certification, and often  practiced beyond the regulatory reach of the Ministry of Health. Exclusion from formal healthcare providers has not only exposed women who are LMPs to health risks, but has also meant that their pregnancies and births take place without the proper documentary proof that these had occurred in Malaysia.Indeed, many interview participants expressed strong preferences for giving birth outside of a formal medical facility, with a common alternative being giving birth with the attendance of a According to existing literature, the decision to have home births might typically be attributed to sociocultural factors, such as distrust of mainstream institutions by rural-based or uneducated mothers. However, it was not uncommon for women to have given birth inside a medical institution in their home countries, or prior to the hiking of foreigner fees in Malaysia, and then later having to resort to home births due to financial constraints. These patterns suggest that migrant women might have opted for within-institution births if it had been financially feasible to do so. For example, one Timorese Indonesian mother of four gave birth to her first two children in a government hospital in Sabah at a time when hospital fees were still manageable. Her third and fourth children, however, were born at home after it became unaffordable to give birth at the hospital.Other women referenced instances of relatives or neighbors struggling with financial burdens after giving birth in a hospital, which informed their own decisions to attempt home births. One Filipino Muslim woman recounted how her daughter-in-law was invoiced 3000 Ringgit ($750 USD) by the government hospital for her emergency breech delivery. She stated that even vaccinations, which cost 40 Ringgit ($10 USD) each for non-Malaysians, would be difficult to afford for poor migrants, such as herself.bidan and would only go to the hospital in the case of an emergency during labor. She alluded to the compounded difficulties of being not only a foreigner but one without legal status: “Because we do not have passports, we need to pay an expensive fee. It’s so hard without a passport.” Witnessing or hearing rumors about family, friends, and neighbors being served exorbitant bills by hospitals—and, in some cases, nevertheless having adverse pregnancy outcomes—served to discourage some interview participants from frequenting clinics and hospitals themselves.One pregnant Timorese Indonesian, who was 19 years at the time of our interview, was determined to give birth with the assistance of a Financial barriers arising from their legalized exclusion exerted a comparatively more indirect influence on households when it came to birth registration. LMPs who are mothers are disincentivized from registering their children’s births in part by the high opportunity costs associated with attempting to do so. To reiterate an earlier point, in the Malaysian context, birth registration is not an automatic process. That is, the onus falls upon the child’s parents to travel to the National Registration Department to apply for a birth certificate. Extensive and stringent documentary evidence is required to register a birth; without this evidence, applications are denied  by the authorities on the way to or even at the hospital. The concern among irregularly statused households that hospitals could function as surveilling agents is a legitimate one. In September 2001, the Ministry of Health released a circular to state health directors outlining guidelines for the reporting of pendatang tanpa izin  to the police by all staff members employed by the Ministry.For example, Maria, a stateless woman of East Timorese descent who was pregnant for the first time, was discouraged by her mother-in-law from planning to give birth at the hospital in the nearest town. Maria was born in Sabah to undocumented immigrants from Indonesia who had come to Sabah to work on a palm oil plantation. Without a birth certificate or any other form of documentation, and having never been to Indonesia, Maria felt that her stateless status is not reflective of her affective ties to Malaysia. Maria decided to heed her mother-in-law, an Indonesian migrant worker with an expired visa, who feared that Maria would get Contrary to the commonly expressed belief among development agencies and even scholars that marginalized families do not apply for birth certificates for their children out of ignorance, the families we spoke to were highly aware of the importance of securing their children’s legal identity through birth registration. The lack of documentation and legal status constrained LMPs in many aspects of their lives, serving as constant reminders of the stakes involved in failing to obtain documentation for their newborn children. Likewise, pregnant mothers placed high value on formal prenatal and obstetric services, regardless of whether they were able to afford them. Rather than explain away unregistered births and out-of-system pregnancies as consequences of lack of knowledge or awareness on behalf of uneducated and impoverished parents, we instead draw attention to the political and legal forces that constrain individuals’ abilities to act in their own and on behalf of their families’ best interests.Legalized exclusion from the public safety net and fears of arrest informed LMPs’ perceptions of their ineligibility for accessing both health care and registering services due to their irregular status. “It’s hard for non-citizens,” said Mariana—a young expectant mother who was born in Indonesia but brought to Sabah as a child—with regard to accessing hospitals. “Even if you have a valid passport, you need to pay an expensive fee to go to the hospital,” she reflected, going on to note that she did not even have a passport, valid or expired. Another Indonesian migrant couple explained that they did not have birth certificates for their youngest three children, because they were all born at home. Without proof from the hospital that their children were in fact born on Malaysian soil, the couple knew that any attempts to apply for birth certificates for them would be refused by the National Registration Department.Knowledge about legal eligibility for subsidized health care, and about the documentary requirements for registering births in Malaysia, were circulated via social and familial networks. Families also acquired awareness of their legal and bureaucratic constraints through failed firsthand attempts at applying for birth certificates or accessing health services. In the next section, we discuss the major challenges that LMPs encountered upon deciding to make institutional contact with public healthcare providers or registering bodies.Thaddeus and Maine  define PIn the foregoing section discussing Phase I delays, LMPs were discouraged from venturing into public spaces due to fears of arrest, detention, and possible deportation. For those who decide to take the risk—for example, in cases of health emergencies—potential apprehension presents itself at every step of the journey, rendering illegality a major constraint to geographic mobility.Roadblocks are one strategy employed by the Malaysian authorities for finding unauthorized immigrants. In 2020, after the outbreak of the COVID-19 pandemic, the government launched Ops Benteng, a joint operation involving the Armed Forces, the Royal Malaysian Police, the Malaysian Maritime Enforcement Agency, and the Malaysian Border Control Agency to “ensure the country’s borders are safeguarded, and to eliminate cross-border crimes and to prevent the spread of COVID-19.”13The spatial distribution of public services in relation to the residential patterns of LMPs is not random or accidental but politically designed. In this section, we note that the Malaysian National Registration Department is not the only governmental body that has registering capacities. People of Filipino and Indonesian descent can theoretically avail themselves of civil registration and passport services provided by their countries’ consulates. We describe this access as theoretical, because it is not feasible for the vast majority of immigrants and their families to bridge the geographical gap that separates foreign nationals from their consular representatives.akta kelahiran (birth certificates). These efforts are supported by local civil society actors, who conduct much of the local grassroots organizing prior to the arrival of consular missions. However, the demand for consular assistance far outpaces the frequency of these missions, leaving families without consular assistance for months at a time or potentially without ever receiving assistance.In the case of Indonesian migrants, the Indonesian government has two consular offices in the state of Sabah: one in the capital city of Kota Kinabalu, and the other on the opposite coast in the city of Tawau. Indonesian migrant workers, particularly those living on remote palm oil plantations in the interior of the state, are often unable to travel to these urban centers for the various legal and resource-related reasons already discussed. To expand their service coverage, Indonesian consular representatives often arrange outreach missions to remote plantation areas to conduct campaigns to supply Sabah-born children of Indonesian descent with documents called The Filipino consulate also conducts regular outreach missions on a rotating schedule of locations across Sabah, which are commonly learned about by word of mouth or on social media. In contrast with the Indonesian government, however, there is no permanent diplomatic presence of the Philippines on Sabahan soil owing to long-standing competing political claims over the territory of Sabah between the Filipino and Malaysian governments  were bureaucratic in addition to geographical. For legally marginalized populations seeking to obtain birth certificates for their children, the process is often circuitous and riddled with dead ends, resulting in long delays or unsuccessful registration outcomes.To obtain a Malaysian birth certificate, families must be able to furnish several pieces of supporting documentary evidence , as she is a non-citizen according to her birth certificate. When it came time to enroll her son in primary school, his birth certificate was allegedly confiscated by an education officer who questioned the boy’s right to attend a government school. By then, the boy’s father had become estranged from the family, leaving Hasnia the sole caregiver to their son. When Hasnia went to the National Registration Department and attempted to obtain an extract of her son’s birth certificate, bringing along with her a photocopy of the original, she was, according to her recollection, accused by the officer of attempting to fraudulently obtain a birth certificate. Without legal status of her own and thus fearing for her safety, Hasnia fled the office and has avoided government officers ever since. Her son remains without possession of his birth certificate.Without valid legal status, LMPs in Sabah were at times met with threats of arrest upon arrival at healthcare facilities or registering offices, though such occurrences were comparatively rare in our fieldwork. Hasnia, a Sabah-born stateless woman of Filipino descent, gave birth to a boy in 2011. The boy’s father, a member of the While frontline healthcare providers, such as doctors and nurses, tended to be less discerning of patients’ legal status due to a professional obligation to provide care to the best of their ability, hospital administration staff faced greater pressure to assess individuals’ ability to afford care. People of Filipino and Indonesian descent, especially those with lower socioeconomic status, contend with presumptions of undocumented status in their everyday interactions, a process that scholars have described as the “racialization of illegality” . That iOther participants reported being able to give birth at government hospitals but were saddled with hefty fees afterwards. Wati, an Indonesian woman with an expired passport, recalled being charged 1700 Ringgit ($425 USD) for a normal birth and a 1-day stay at the hospital, which she estimated to be equivalent to around 3-month salary for her household. Though her family is striving to pay off their debt to the hospital in instalments, Wati harbors shame from the experience. “People can still give birth at the hospital if their passport has expired, but the staff at the hospital will be angry,” Wati recalled when describing the belittling treatment she received as an undocumented patient. “They will ask, ‘Why did not you renew your passport?’”Even when frontline workers are properly doing their jobs, formal laws and administrative procedures work to perpetuate the disadvantage and exclusion of LMPs. In our discussion of Phase I delays, we detail study participants’ sense of futility in being able to register their children or afford public health services due to insufficient documentation. This anticipation of rejection is not merely borne out of conjecture. As we show in our section on Phase II delays, households expended significant amounts of time, energy, and money trying—and often failing—to satisfy government agencies’ documentary requirements. Delays in Phase III stem from the stringent bureaucratic requirements that are enforced at the National Registration Department and other governmental bodies, which structurally disadvantage legally marginalized populations.In addition to passports and visas, participants commonly identified prenatal health cards as an essential document, as well as one that was difficult to obtain. Being in possession of the full repertoire of documents would require women not only to give birth inside a healthcare facility, but also to be in regular contact with healthcare providers throughout the prenatal stage. In our ethnographic observations, we witnessed parents being summarily turned away from National Registration Department counters if they did not possess all the documents required for birth registration, even if they had brought their babies with them. The high burden of documentary proof demanded by the National Registration Department stems from political pressures to safeguard Malaysian citizenship from “illegal” immigrants. The politicization of birth registration in Sabah, however, has led to the deprivation of the fundamental right to a legal identity among children born on Malaysian soil.The “inter-linkages and integrated nature of the SDGs” reflect the belief that poverty eradication with the aim to “leave no one behind” requires a holistic and inclusive approach (United Nations, This being said, such experiences of exclusion do not affect all non-citizens equally or in the same way across Malaysia. The legally marginalized population in Malaysia is not homogenous, and their experiences and characteristics vary significantly. LMPs in Sabah have experiences that are distinctive from LMPs in Peninsular Malaysia due to the historical politicization within the state of immigration- and particularly documentation-related issues, as well as the protracted nature of citizenship exclusion among various communities. LMPs within Sabah itself can be further disaggregated into groups with distinctive vulnerabilities. Indonesian migrants, for example, have comparatively better access to Indonesian consular services in Sabah compared to Filipino migrants, whose government does not have a permanent consular presence in the state for political reasons. At the same time, persons of Filipino descent whose ancestors, or who themselves, had fled Mindanao to Sabah during the 1960s and 1970s are eligible for Sabah government-issued IMM13 cards as de facto recognition of their status as asylum seekers, which provides a modicum of rights that immigrants from other countries and time periods do not have. IMM13 eligibility and recognition, however, is temporary and is liable to be paused or revoked at the will of the state government. It is also important to distinguish between irregular migrants and their children who may be eligible to claim a nationality—for example, migrant workers whose visas have lapsed but who may still possess familial, cultural, or even documentary ties to their sending countries—and those in Sabah who are without any viable pathways out of being stateless—such as descendants of IMM13 refugees or undocumented foundlings. Thus, access to health care, birth registration, and other rights and protections must be considered through an intersectional lens and with consideration for the particular nature of legal exclusion that different non-citizen minorities face in Sabah and in Malaysia as a whole.This leads to questions about the extent to which, and how, the integrated three delays model can be generalized beyond the Sabah context. Sabah may upon first glance seem like an outlier in terms of the number, long-standing nature, and vulnerability of its non-citizen members. However, this case is an example of broader global trends in recent years of rising international displacement, particularly among countries in the Global South (International Organization for Migration, Enhancing protections for the health of non-citizens and lowering administrative barriers to civil registration will contribute to improving maternal and infant health, empowering governments’ abilities to monitor population health, and reducing the occurrence of statelessness. Measures that governments can take to improve the right to health and to a legal identity include adopting more flexible and inclusive bureaucratic requirements for registering births and other events—such as community-based approaches to verifying the occurrence and characteristics of a child’s birth—to lower barriers to the recognition of LMPs. Both sending and receiving states should coordinate with one another to improve protections for the right to health among migrants, including overseas migrant workers, and their children. This includes providing affordable and accessible health insurance and expanding both emergency and preventative maternal health services to migrant families.Research about the causes and consequences of exclusion from CRVS systems is rapidly growing in the Sustainable Development Goals era, garnering wide interdisciplinary interest. While our qualitative approach enables us to detail and trace the complex factors and processes that lead to under-registration or out-of-system births, our small sample size prevents us from generating any reliable statistical estimates of the scale or prevalence of these phenomena. Second, our model is based on a single case study and cannot necessarily be generalized to other cases without first making adaptations to suit their particular legal and administrative contexts or demographic compositions. That being said, our qualitative study is intended to complement well-established quantitative demographic research in this subfield and to serve as a call for the continued methodological diversification of inquiries into CRVS-related issues.


Background: Twin pregnancies are associated with an increased risk of adverse maternal and neonatal outcomes, mainly owing to prematurity. Few studies have evaluated the risk factors for preterm birth (PTB) in Chinese population. The objective of this study is to present the short-term maternal-neonatal outcomes, investigating the potential risk factors associated with preterm birth in Chinese twin pregnancies.Methods: A multi-center retrospective study of women pregnant with twins ≥28 weeks of gestation was conducted. Maternal and neonatal outcomes were analyzed. Logistic regression was used to identify potential risk factors for PTB before 37, 34, and 32 weeks, respectively.Results: A total of 3,288 twin pregnancies and 6,576 neonates were included in 99,585 pregnancies. The rate of twin pregnancy was 3.3%, while the PTB rate before 37, 34, and 32 weeks among this population were 62.1, 18.8, and 10.4%, respectively. Logistic regression revealed that monochorionicity , gestational weight gain (GWG) <10 kg  and GWG between 10 and 15 kg , preeclampsia (PE) , and intrahepatic cholestasis of pregnancy (ICP)  were the risk factors for PTB before 37 weeks. Monochorionicity , age < 25 years , and GWG <10 kg  were risk factors for PTB before 34 weeks. Monochorionicity , age younger than 25 years , and GWG <10 kg  were the risk factors for PTB before 32 weeks.Conclusions: Monochorionicity and GWG <10 kg were two major risk factors for PTB before 32, 34, and 37 weeks, whereas maternal age, PE, and ICP were also risk factors for PTB in specific gestational age. Globally, twin pregnancies account for ~2–4% of all births and it has been reported that the incidence has increased dramatically over the past few decades –4. PatieA better understanding of perinatal maternal and neonatal complications and outcomes of twin pregnancies will undoubtedly enhance clinical practices. In addition, the proper identification of patients at higher risk of preterm birth would enable optimization of the available interventions to reduce the adverse perinatal outcomes associated with preterm birth. Meanwhile, the availability of a risk stratification system will help to decrease unnecessary interventions in low-risk patients and improve the therapeutic efficiency in those at high risk of preterm birth. Methods for predicting preterm birth and risk factors for preterm birth in twin pregnancy have long been studied. A history of preterm birth , maternaHowever, research involving twin pregnancies is mainly conducted in western countries, and data on the perinatal outcomes of twin pregnancies among Chinese women are limited; few studies have evaluated the risk factors for preterm birth in this large population. We aimed to analyze the maternal and neonatal outcomes among Chinese twin pregnancies in a large multi-center cohort and to identify the potential risk factors for preterm birth in this population.This study was conducted in 14 representative medical centers  from 10 provinces in the four major economic regions of China from October 1, 2016 to September 30, 2017. Complete medical information for each birth, including maternal demographics, medical and obstetric history, and maternal and perinatal outcome information were retrospectively registered into a prospectively designed network-based standardized data acquisition system obtained from digital and written medical records. The medical records from the 14 participating hospitals in this study were standardized before the research was initiated. This retrospective birth registry study was approved by the Ethics Committee of Peking Union Medical College Hospital . The need for informed consent was waived due to the retrospective nature of the study. All pregnant women aged 18–55 years, who had their first antenatal visit in the first trimester and gave birth to twins ≥28 weeks of gestation, were eligible for inclusion. Women without data on the exact age and gestational age at delivery were excluded. Data including demographic factors, clinical characteristics including maternal height and weight, GWG, methods of conception, chorionicity, gestational age at delivery, pre-pregnancy and pregnancy complications, medical treatment, pregnancy outcomes, and mode of delivery were collected from the medical records and confirmed by the treating physician. Neonatal birth weight, length, Apgar scores at 1, 5, and 10 min, outcomes  were recorded.2), normal (18.5–23.99 kg/m2), overweight (24–27.99 kg/m2), and obese (BMI ≥ 28 kg/m2) according to the Chinese BMI categorization  . Early pmal 18.5–.99 kg/m2Pre-pregnancy complications referred to a history of preterm birth or late abortion or other related comorbidities such as thyroid disorders, diabetes mellitus, hypertension, liver diseases, iron deficiency anemia, autoimmune diseases, and heart disease. Pregnancy complications included gestational hypertension, preeclampsia superimposed on chronic hypertension, preeclampsia, and eclampsia, gestational diabetes mellitus (GDM), and intrahepatic cholestasis of pregnancy (ICP), and premature rupture of membrane (PROM). Hypertensive disorders of pregnancy (HDP) were classified according to the ISSHP classifications . DeliverThe main outcome of the study was the preterm birth before 37, 34, and 32 weeks in twin pregnancy. The secondary outcomes included maternal pregnancy and delivery complications, and neonatal outcomes. The neonatal outcomes included LBW, SGA, neonatal asphyxia, sIUGR, RDS, admission to NICU, pneumonia, neonatal infection, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), and major congenital malformations.The schedule used for planned delivery in our study was according to the Chinese guideline on the management of twin pregnancy. Uncomplicated monochorionic diamniotic twin gestations underwent delivery between 34 and 37 weeks of gestation and uncomplicated monochorionic monoamniotic twin gestations underwent delivery between 32 and 34 weeks of gestation. In those patients with uncomplicated dichorionic diamniotic twin gestations, we terminated the pregnancy after 37 weeks of gestation. In cases of patients with other complications such as HDP or ICP, the timing of the planned delivery was adjusted according to those comorbidities. Women with mild preeclampsia or chronic hypertension, gestational hypertension were planned delivery after 37 weeks of gestation. The pregnancy was terminated if the condition was unstable or reached 34 weeks of gestation in patients with severe preeclampsia. At ≥34 weeks of gestation, pregnancy was terminated if there were serious complications such as placental abruption, and intrauterine fetal death that threatened maternal and neonatal safety. Pregnancy was also terminated at ≥34 weeks if fetal growth was restricted and accompanied by abnormal umbilical cord blood flow and oligohydramnios. In mild ICP, pregnancy was terminated between 38 and 39 weeks of gestation. In severe ICP, the pregnancy was terminated between 34 and 37 weeks of gestation, but the treatment response and presence of a combination of fetal distress, twin births, or other maternal complications were taken into account.All participants were regularly followed-up by the perinatal health care management teams in corresponding hospitals. The framework for maternal antenatal care was consistent with WHO recommendations and Chinese practical guidelines . Patientt-test or the Mann-Whitney U-test, depending on their distribution. Categorical variables were compared using the chi-squared test or Fisher's exact test. Variables in the univariate analysis with P-values < 0.2 were selected for potential inclusion in the multivariate logistic regression. Forward, stepwise logistic regression was performed to determine potential risk factors for preterm birth. Odds ratios (OR) with 95% confidence intervals (CI) and P-values were calculated. A two-tailed P-value < 0.05 was considered significant. Statistical analysis was conducted using SPSS  or GraphPad Prism (Version 8.0) software.Continuous variables are described by means ± standard deviation (range) if they were normally distributed or as medians and interquartile ranges (IQRs) if they were abnormally distributed. Discrete variables are expressed as counts (percentage). Variables were compared between the two outcomes (preterm birth or full-term birth) using univariate analysis. Continuous variables were compared using the Student's The rate of twin pregnancy was 3.3% in our cohort (mean age: 30.9 ± 4.4 years (range: 18–53 years), mean height: 161.3 ± 4.8 cm). Natural conception occurred in 60.3% of participants, whereas the remaining 39.7% conceived using ART. Sixty-eight patients had a history of preterm birth, with 23 experiencing preterm birth two times or more. Dichorionic diamnioticity  was the most predominant twin subtype, followed by monochorionic diamnioticity , and monochorionic monoamnioticity . The rate of preterm birth < 37, 34, and 32 weeks among this population was 62.1, 18.8, and 10.4%, respectively, with an average gestation of 35.6 ± 2.4 weeks. The incidence of spontaneous and iatrogenic preterm birth before 34 and 32 weeks was 5.0 and 2.8%, and 13.8 and 7.6%, respectively. Other maternal characteristics are listed in Pre-pregnancy complications and complications during pregnancy are also shown in Delivery related complications were also recorded. One hundred and nine patients experienced postpartum hemorrhage , and 91 were severe cases defined as blood loss of >1,000 mL within 24 h after delivery. Management for PPH included arterial intervention embolism (7 cases), uterine B-lynch suture (43 cases), uterine packing (55 cases), uterine arterial ligation (25 cases), and a total hysterectomy (2 cases). Some patients received more than one method of treatment for PPH in our study. There were twin-related complications in 130 patients . Three of the cases of the stillbirth of one fetus were complicated by TTTS. One case of fetal to maternal transfusion syndrome was also noted. No amniotic fluid embolism occurred.After delivery, 12 women were transferred to the intensive care unit but there was no fatality.The mean weight of the 6,576 neonates enrolled in the study was 2,369.3 ± 523.4 g, and their average length was 45.8 ± 3.6 cm. The median birth weight and length were 2,426 g and 47 cm, respectively. The 5, 10, 25, 75, 90, and 95 percentiles were 1,370, 1,650, 2,090, 2,702, 2,950, and 3,100 g for birth weight and 39, 40, 45, 48, 50, and 50 cm, for birth length. The incidence of SGA was 3.7% (204) in our research. Two hundred and eighty-four (4.3%) newborns were diagnosed with asphyxia on delivery, and the incidence of RDS was 1.1% (75 cases). The incidence of Apgar scores <7 and 5 at 1 min was 4.3 and 1.5%, respectively. The average Apgar scores at 1, 5, and 10 min were 9.25 ± 0.8, 9.51 ± 0.9, and 9.60 ± 1.2, respectively. The rate of normal birth weight, low birth weight, very low birth weight, and extremely low birth weight were 44.8 48.3, 6.1, and 0.9%, respectively. Almost half of the newborns were transferred to the neonatal intensive care unit  and 55.5% were uneventfully discharged. Pneumonia (5.0%) and neonatal infection (3.3%) were two common complications among neonates. Respiratory distress syndrome (1.1%), congenital deformity (0.6%), retinopathy of prematurity (0.8%), and necrotizing enterocolitis (2 cases) were also recorded. The perinatal death rate was 0.7%  and GWG between 10 and 15 kg , PE , and  were the risk factors for preterm birth before 37 weeks in further multivariate logistic regression.The results of the univariate and multivariate analyses identified risk factors associated with preterm birth before 37 weeks , univariP < 0.001), age <25 years , and GWG <10 kg  remained statistically significant. Subgroup analysis concerning the impact of chorionicity on spontaneous and iatrogenic preterm birth before 34 weeks are shown in P < 0.001) and 3.037 , respectively.The potential factors for predicting preterm birth before 34 weeks are shown in P = 0.007), height (P = 0.013), chorionicity (P < 0.001), GWG (P < 0.001), and HDP (P = 0.034) were significantly associated with preterm birth before 32 weeks, whereas parity, HDP, and ICP were likely to predict preterm birth. These factors were further used for multivariable analysis, where monochorionicity , age younger than 25 years , and GWG <10 kg  were the risk factors for preterm birth before 32 weeks were statistically associated with increased risk for preterm birth before 32 weeks. Moreover, GWG between 10 and 15 kg slightly increased the risk of preterm birth before 32 weeks . The impact of chorionicity on spontaneous and iatrogenic preterm birth before 32 weeks was also conducted using multivariate logistic regression (P < 0.001) and iatrogenic preterm birth .When we analyzed preterm birth <32 gestational weeks, factors that may affect preterm birth are summarized in gression . CompareP = 0.037). Moreover, the risk for preterm birth before 32 weeks in patients with GWG between 10 and 15 kg were not significantly different compared with those with GWG between 15 and 20 kg. In contrast, GWG above 20 kg was associated with a decreased risk for preterm birth before 32  and 34 weeks . Intrahepatic cholestasis of pregnancy  was associated with a decreased risk of preterm birth before 32 weeks. The incidence of AFLP and autoimmune diseases were too low to be interpreted by logistic regression due to low event rates.There was no significant difference in pre-pregnancy BMI and proportions of different pre-pregnancy BMI categories between patients with or without preterm birth before 32, 34, and 37 weeks of gestation. However, some factors associated with reduced risk of preterm birth were also identified by logistic regression analysis. Maternal height ≥170 cm appeared to be a protective factor for preterm birth before 37 weeks . The need for informed consent was waived due to the retrospective nature of the study.SL wrote the manuscript and participated in data analysis. JHe, YT, XL, and YC conducted data collection and quality control at their medical centers. JHu and XC participated in data analysis. JG conceived and designed the study. JL participated in designing the study and revising the language. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Variations in cardiovascular disease risk (CVD) are suggested to be partly influenced by factors that affect prenatal growth patterns and outcomes, namely degree of maternal investment . Using the life history trajectory model, this study investigates whether maternal investment in early prenatal life associates with menarcheal age and whether maternal investment affects CVD risk in adulthood and predicts adult size and adiposity levels.A cross-sectional study was conducted among 94 healthy Emirati females. Birth weight, gestational age and menarcheal age were obtained. Anthropometrical measurements, body composition analysis, and blood pressure values were collected. Regression analyses were conducted to establish associations.β = 1.342 cm, 95% CI , p = 0.032) and leg length , p = 0.034). Menarcheal age was significantly and inversely associated with fat mass index (FMI) , p = 0.002), but not with waist circumference and fat free mass index (FFMI) (p > 0.05). Birth weight SDS was positively and significantly associated with waist circumference , p = 0.009), FMI , p = 0.027), and FFMI , p = 0.003). Birth weight SDS was not significantly associated with either systolic blood pressure (SBP) or diastolic blood pressure (DBP) (p > 0.05). However, FMI, waist circumference, and FFMI were positively and significantly associated with SBP. Regarding DBP, the relationship was negatively and significantly associated with only FFMI , p = 0.002).There was no association between birth weight standard deviation score (SDS) and age at menarche. When investigating the associations of birth weight SDS and age at menarche with growth indices, it was found that only birth weight was positively and significantly associated with both height (Although the results do not fully support that Emirati females fast-life history is associated with increased chronic disease risk, the data does suggest a link between restricted fetal growth in response to low maternal investment and metabolic and reproductive health.The online version contains supplementary material available at 10.1186/s12889-021-11182-0. Current World Health organization (WHO) statistics have reported Cardiovascular Disease (CVD) to be the leading cause of mortality worldwide with an estimation of 17.9 million deaths each year . The aetHypertension is a highly prevalent condition that affects up to 1.13 billion adults all over the world and is highly incriminated in increased risk of CVD amongst other chronic conditions . Normal Adiposity-related health consequences are well known and documented, and high adiposity levels have been linked to numerous chronic diseases including CVD . Body MaThe risk factors explored above are only able to predict disease risk up to a limited point. So far, the lifestyle model has only been successful in partly explaining CVD risk by exploring lifestyle interactions with underlying genetic influences . Other tHales and Barker , in accoAlthough past studies have shown that biological programming in prenatal life as a response to nutritional affluence or lack of is an important factor to consider, it is important to also take into account how lifestyle measures later on in life affect the degree of disease manifestation. To address this issue, Wells et al.  went on  faster pace of life history  lower adult height, higher energy stores for reproduction and lower metabolic health. In other words, low birth  weight earlier maturation + shorter height  later increased adiposity. The opposite holds true for those receiving high maternal investment and optimal nutrition in fetal life [During critical windows in gestation, “epigenetic processes are thought to alter gene expression in the fetus based on maternal environmental cues”  in ordertal life . In 2018tal life . Bleil etal life  reportedtal life . Anothertal life . Maternatal life . For thetal life .Low birth weight, which is an indicator of poor fetal growth and low maternal investment, has been found to result in lower fat free mass (FFM) in adulthood –40. ThisTo the best of our knowledge, this study is the first one of its kind in the UAE. It investigates how maternal investment shapes the life history pace of the offspring. This will offer us a chance to study the extent that maternal investment influences life history pace and generates the trade-off between maturation/adiposity versus growth/homeostatic maintenance. It then looks at whether this trade-off increases risk of CVD in adulthood.Those who were on the receiving end of poor maternal investment (characterized by lower birth weight standard deviation score (SDS)) during the fetal period would develop earlier maturation (proxied by earlier age of menarche).Lower maternal investment, coupled with an earlier maturational timing (proxied by earlier age of menarche), would then lead to reduced growth .Lower maternal investment, coupled with an earlier maturational timing (proxied by lower birth weight SDS and earlier age at menarche), would then lead to elevated CVD risk  and lower fat free mass index (FFMI).Reduction in metabolic capacity (proxied by low birth weight) in addition to a high metabolic load (proxied by elevated adult adiposity and lower FFMI) would lead to higher risk of CVD (proxied by elevated BP).In healthy women from the UAE, based on the interpretations of the life history theoretical framework, we hypothesized that:This was a cross-sectional study that involved 94 females aged between 17 and 27 years with a gestational age exceeding 37 weeks. The study used convenience sampling method for selecting healthy, Emirati females enrolled in various governmental (public) universities in the UAE. The consent of participants was obtained, and data collection was carried out in the body composition laboratory at Zayed University, Dubai-UAE. The study was reviewed and received full ethical clearance by the Zayed University Research Ethics Committee (ZU16_016_F). Exclusion criteria included current smokers, twins, pregnant or lactating females, those with metal parts in their body , those who reported a weight gain or loss of more than 3 kg in the 3 months leading up to the screening, and those with medical conditions known to impact body composition or metabolism such as diabetics, renal patients, hypertensives and females with hormonal imbalances.A structured questionnaire was used to obtain personal data such as date of birth, sex, ethnicity, marital status, birth order, gestational age, weight at birth, menarcheal age, medical history, list of medications taken if any, and family history of disease . The difference between sitting and standing height was then calculated to represent leg length . Both si2. WHO classifies overweight as BMI values between 25 and 29.9 kg/m2, and obesity ≤30 kg/m2 [2 and FFMI = fat free mass (kg)/height (m)2.Waist circumference was measured at the narrowest position using a nonelastic flexible tape, taken to the nearest 0.1 cm over light clothing . BMI was30 kg/m2 . The use30 kg/m2 ; therefo30 kg/m2 . These v30 kg/m2 . FMI is BP was measured using an automatic monitor  whilst the subject was seated. The reading was taken three times (a few minutes apart) and the average of the 3 measurements was used in analysis. The American Heart Association (AHA) classifies hypertension as > 140 mmHg systolic and > 90 mmHg diastolic .p–values < 0.05 were considered statistically significant.Data was analyzed using Statistical Package for the Social Sciences (SPSS) software Version 27. Birth weight was adjusted for gestational age, where birth weight SDS were calculated using the LMS method . Linear A total of 94 participants were recruited in this study. Due to 6 missing measurements, the analysis for sitting height and leg length was done on 88. The mean age of the participants was 19.9 years, while the mean birth weight was found to be 3.1 kg. All those analyzed were born to term according to conventional criteria (> 37 weeks gestation). Regarding BMI, 19 participants (20.2%) were found to be overweight and 8 (8.5%) were obese, and 12.8% had a waist circumference measurement equal to or above 80 cm, which classifies them as having an increased risk of metabolic complications  according to WHO classifications . The meaβ= − 0.184 years, 95% CI , p = 0.261).Table β = 1.342 cm, 95% CI , p = 0.032) and leg length , p = 0.034). Age at menarche, on the other hand, did not show the same relationship with both growth indices (Table When investigating the associations of birth weight SDS and age at menarche with growth indices (height and leg length), it was found that birth weight SDS was positively and significantly associated with both height , p = 0.002), indicating higher adult adiposity with earlier puberty. Menarcheal age was not significantly associated with waist circumference and FFMI (p > 0.05). On the other hand, birth weight SDS was positively and significantly associated with waist circumference , p = 0.009), FMI , p = 0.027), and FFMI , p = 0.003). The highest birth weight SDS is predicted to be associated with 1.16 cm increase in waist circumference compared to the lowest birth weight SDS. This is not an insignificant amount, though it is within the sample’s standard deviation in waist circumference which is 9.4 cm. When age was accounted for in the models, it showed significant result only with FFMI , p = 0.011). In this same model, age at menarche showed significant association with FFMI as well , p = 0.029), where β-coefficient of age at menarche dropped from − 0.181  to − 0.222  with a change in p-value to < 0.05. When duration of breast feeding (months) was introduced to the models, positive but not significant associations were found (p > 0.05) with waist circumference, FMI and FFMI.Table p > 0.05). However, all indices of adult adiposity (FMI and waist circumference) and FFMI were positively and significantly associated with SBP. Regarding DBP, the relationship was only negatively and significantly associated with FFMI , p = 0.002). When age was introduced to the BP regression models, no significant changes in the associations were found.Table p > 0.05). Birth weight SDS was positively and significantly associated with waist circumference, FMI, and FFMI. All indices of adult adiposity (FMI and waist circumference) and FFMI were positively and significantly associated with SBP. Regarding DBP, the relationship was negatively and significantly associated with FFMI only.This study was set out to test the hypothesis that maternal investment in utero would shape the life history pace of the offspring. An accelerated life history pace  would cause the individual to prioritize reproduction overgrowth and homeostatic maintenance. In other words, the individual develops higher energy stores for reproductive purposes, and present with reduced growth and increased risk for chronic disease through poorer BP regulation, lower FFMI and higher central adiposity. In a sample of 94 young Emirati women (17–27 years), our results showed that birth weight SDS was positively and significantly associated with both height and leg length, while age at menarche did not show the same relationship. Body fat was inversely associated with menarcheal age, but not waist circumference . Leg length was not significantly predictive of FFMI, FMI, SBP, and DBP. Additionally, those born small for gestational age and achieving shorter height were found to be associated with elevated sympathetic nerve activity [Moreover, our findings support the hypothesis stating that lower maternal investment (lower birth weight) is linked to reduction in growth (proxied by height and leg length). This finding is consistent with earlier studies that reported the effect of birth weight on adult height , 59. Thiactivity . This isactivity ; not excIn our analysis, lower birth weight was not linked to elevated adult adiposity levels, in fact the data showed the opposite association: the higher the birth weight, the higher the adult central adiposity (waist circumference). On the other hand, an earlier menarche was found to be associated with higher adult adiposity markers when adjusted for age. Our results are consistent with other findings reported in the meta-analysis conducted by Prentice and Viner in 2013 . HoweverClinical and experimental studies revealed that IUGR is associated with a significantly higher incidence of metabolic, renal and CVD in adult life where ‘IUGR directly cause cardiovascular alterations independent of pre-existing metabolic disease’ . It has However, indices of adult adiposity were found to be positively and highly significantly linked to SBP. This stresses the importance of ‘metabolic load’ and post-natal environmental stressors on the development of disease rather than just birth weight. It is also important to note that while some studies have supported the link between birth weight and increased blood pressure, these findings were inconsistent. A study looking into the association between intrauterine growth and obesity suggested that it could be more useful to assess weight at birth “relative to genetic potential, indicated by the size of the parents or by the individuals body height” . This isWaist circumference was found to be positively associated with birth weight SDS. This indicates that higher birth size equates to higher adult central adiposity. Some studies had found inverse associations between birth weight and abdominal obesity in adulthood than not –18.Size at birth was also significantly and positively associated with FFMI. To explain why those who are born smaller end up with less adult fat free tissue mass, it has been suggested that suboptimal nutrition in prenatal period would restrict insulin secretions by causing hypoglycemia and so an upsurge in protein breakdown and a reduction in protein accretion . AnotherIt is important to note that although this type of study may offer us a chance to explore the links between maternal influences in prenatal period and adult disease risk, the issue remains much more multifaceted and there exist numerous limitations that make interpretation more complex. It is difficult to determine whether the heightened risk was due to lack of maternal investment and not attributable to other influences.There were several limitations to the study. First, our study was cross-sectional, hence the inability to make causal relationship between early life events and their effect on later life outcomes . Second,This is a pioneer study in the UAE that sheds the light on the link between the intrauterine environment and potential disease risk. Although the study did not provide evidence for the proposed link between degree of maternal investment and menarcheal age, predictors of low maternal investment resulted in shorter height in adulthood. Earlier maturation was linked to higher adult adiposity but was not indicative of fat distribution. As for CVD risk, elevated blood pressure and adult central adiposity were linked to higher birth weight and/or gestational age, negating the hypothesis that weak maternal investment would result in hypertension. On the other hand, those born small were found to have lower FFM, which is indicative of higher CVD risk through possible interaction with glucose uptake mechanisms. Higher adult adiposity was also found indicative of higher SBP. This reiterates the role a higher metabolic load has on risk of disease. Over the past years, the UAE has witnessed developmental leaps and considerable changes in different life aspects naming health, economy, industry, education and most importantly lifestyle and eating habits . What maAdditional file 1. Questionnaire and data collection form.


MYO5B or STX3 gene. MVID is a disease that is difficult to manage with clinical heterogeneity. Therefore, knowledge about factors influencing MVID morbidity and mortality is urgently needed. Triggered by a recent study that reported a high percentage of preterm births in twelve cases of MVID, we have conducted a comprehensive retrospective study involving 88 cases of MVID with reported gestational ages. We found that moderate to late preterm birth occurred in more than half of all cases, and this was particularly prominent in MYO5B-associated MVID. Preterm birth in MVID counterintuitively correlated with higher birth weight percentiles, and correlated with higher stool outputs and a significantly shorter average survival time. Data from this study thus demonstrate an increased risk of preterm birth in MYO5B-associated MVID, with a clinical impact on morbidity and mortality. Adverse effects associated with preterm birth should be taken into account in the care of children diagnosed with MVID. Documentation of gestational age may contribute to a better prognostic risk assessment in MVID.Microvillus inclusion disease (MVID) is a rare enteropathy caused by mutations in the  MYO5B gene [STX3 gene [STXBP2 gene [Microvillus inclusion disease (MVID) is a rare enteropathy ,2. MVID O5B gene  or bi-alTX3 gene  in ~95% TX3 gene . SymptomBP2 gene , but becMVID is uniformly fatal if left untreated. Treatment is only supportive and involves life-long maintenance of nutrition and hydration with total parenteral nutrition (TPN). Prognosis is generally poor, and most patients die within one year after birth, mostly due to sepsis or liver disease . With moRecently, Caralli and colleagues  noted a To collect all published reports on cases of MVID, we searched EMBASE and MEDLINE databases using the following search strings: ((microvill* inclusion disease) OR (microvill* atrophy)) AND case report). Data from these cases were manually analyzed (using the ‘find’ tool in Adobe reader) with regard to preterm birth (defined as parturition prior to 37 weeks of gestation) , sex, bip < 0.05. The Mann–Whitney U test was used for non-normally distributed data sets. Levene’s test was used to determine homogeneity of variances. The Shapiro–Wilk test was used to determine normality. Sex-corrected birth weight percentiles were calculated at https://www.audipog.net/Courbes-morpho. Graphs were generated at https://canva.com/graphs and with MS Excel (2103 (16.0.13901.20400)/accessed on 13 April 2021).Odds ratios (OR) were calculated as measures of association. Statistical analyses included chi-square test with Yates correction to prevent the overestimation of statistical significance for small data, Pearson’s correlations and Student’s or Welch’s two-tailed t-tests to determine statistical significance, assuming a priori statistical significance when Due to the retrospective nature of this study, data were missing in several variables because of incomplete data recording. Because our aim was to simply describe and compare subgroups of patients with different gestational ages , no method for missing data was utilized.p < 0.0001). Of the preterm births in MVID, 91% (42/46) were categorized as moderate to late preterm birth (33+0–36+6 weeks gestation)  A.X2  = 0.0443, p = 0.83).Of the preterm births in MVID for which the mode of delivery was documented, 84% (27/32) were spontaneous . Medically indicated factors linked to late preterm birth, such as intrahepatic cholestasis during pregnancy, maternal diabetes, placental abruption, placenta previa, hypertension, preeclampsia, intrauterine growth restriction or multiple gestation, were not or rarely reported. Polyhydramnios (defined as an excess amount of amniotic fluid) was reported in 22% (12/55) of MIVD patients, for which the presence or absence of polyhydramnios was documented. However, there was no significant difference in the occurrence of polyhydramnios between preterm and term births in MVID (t (62) = −4.36, p = 0.00005) (t (46) = 2.96, p = 0.005). Forty-one percent (12/29) of preterm birth weights in MVID were above the 80th centile (for term MVID cases this percentage was 12% (2/17))  (The average birth weight of MVID patients was significantly lower in preterm born patients (2584 ± 612 g versus 3191 ± 485 g (mean ± SD) for preterm and term births, respectively; 0.00005) B. Gestat0.00005) C. Notabl= 0.048) D, albeitTogether, MVID is associated with an increased risk of idiopathic preterm birth and a therewith associated higher average birth weight percentile.STX3 mutations were born preterm [MYO5B mutations were born preterm -type 6 [Bi-allelic )-type 6 ,20. Nota)-type 6 ,20.MYO5B mutations, but that not all bi-allelic MYO5B mutations increased the risk of preterm birth.These results indicate that preterm birth in MVID appeared restricted to patients with bi-allelic Clinical characteristics of MVID, such as time of onset, extent of diarrhea, TPN dependency, intrahepatic cholestasis, neonatal respiratory distress and time of death display a poorly understood inter-patient heterogeneity ,11,21. Wt (70) = 0.364, p = 0.36), but a higher average stool output was observed in preterm births when compared to term births  = −2.15, p = 0.02)  A. All MVNeonatal respiratory distress has been reported in several cases of MVID, but how often it occurred in MVID has not been investigated. In our MVID case report collection, neonatal respiratory distress was reported in 16% (14/88) of cases of MVID, often preceding the onset of diarrhea and requiring assisted ventilation. In the remaining 74 cases, there was no mention of respiratory distress, meaning that respiratory distress either did not occur or did occur but was not known to the authors. Notably, all but one of the fourteen respiratory distress cases were associated with preterm birth (range: 34–36 weeks), indicating that respiratory distress occurred in at least 28% (13/46) of preterm births in MVID.MYO5B mutations carried by the patient and/or may be a complication of the TPN [A life-threatening extra-intestinal symptom of MVID is intrahepatic cholestasis ,22,23. I the TPN ,22,23,24t (38) = −3.26, p = 0.0329), but not birth weight (r (27) = 0.1499, p = 0.46) or stool output (r (34) = −0.045, p = 0.79), was associated with a shorter average survival time (6.25 months for preterm births versus 16.31 months for at term births)  B.This retrospective study revealed moderate to late preterm birth in more than half of all reported MVID cases. This is ~5-fold higher when compared to the world average (~10%) . On a caModerate to late preterm birth is generally associated with higher rates of infant morbidity and mortality when compared to full term birth . A higheThe gastrointestinal system is subject to rapid growth and maturation in the final weeks before birth. Consequently, moderate to late preterm birth is associated with immaturity of the gastrointestinal system. Preterm birth can be expected to contribute to, aggravate or complicate gastrointestinal symptoms in MVID neonates.Neonatal respiratory distress was noted in at least one third of all reported moderate to late preterm MVID births. The risk of respiratory distress associated with preterm birth in general is well known, but it occurs predominantly in early preterm birth and much less in moderate to late preterm birth . The reWhy MVID patients were at risk of preterm birth is an outstanding question. There was no correlation between preterm birth in MVID and reported maternal risk factors or complications during pregnancy. Antenatal symptoms  occurredSeveral maternal factors associated with preterm birth risk, such as maternal age, size or smoking behavior were not typically reported in published case studies. However, there is no reason to believe that these factors were unevenly distributed between parents of MVID patients and non-MVID patients. It is also unlikely that the high percentage of preterm birth in MVID was related to the patients’ country of origin, as the range of average preterm birth percentages between high- and low-income countries is 9–12%, respectively, and none of the reported MVID patients originated from world regions with the highest preterm birth rate .SLC26A3 mutations was associated with very (29%) and moderate to late (59%) preterm birth, polyhydramnios and IUGR [MVID belongs to a subgroup of congenital diarrheal disorders ,31. Thesand IUGR . While land IUGR , MVID waand IUGR , suggestMYO5B mutations may be independent risk factors for preterm birth. Little is known about genes associated with preterm birth [MYO5B mutations. We found no link between MYO5B and other genes associated with diseases with preterm birth as a phenotype . Interestingly, EBF1, which encodes a transcription factor for—among many others—MYO5B, was identified in a genome-wide association study searching for loci associated with gestation age and preterm birth [MYO5B gene on embryonal and fetal development, and on the function of the placenta in which MYO5B is highly expressed . Such studies may contribute to a better understanding of genetic and cell biological mechanisms that can lead to preterm birth.Possibly, some rm birth . Pretermrm birth . As timiMYO5B-associated MVID, and, moreover, put this finding in a clinical perspective with regard to MVID morbidity and mortality. Preterm birth and therewith associated adverse effects should thus be considered in the care of children diagnosed with MVID. Documentation of gestation age may contribute to a better prognostic risk assessment in MVID.In conclusion, we demonstrated a high percentage of idiopathic preterm births in


Transcutaneous electrical nerve stimulation (TENS) has been used as analgesic therapy in many diseases. It is already known that studies that have observed the relationship between pain and cytokines have found that patients who report less severe pain have less production of proinflammatory cytokines. However, one another accepted mechanism is that decreasing proinflammatory cytokines results in decreased pain intensity. Analyzing the literature, the authors describe that, in addition to the analgesic effect, TENS has shown systemic effects, and clinically, the reduction of proinflammatory cytokines could be a protective factor against inflammation. To test the inflammatory effect of TENS, we researched the literature for clinical conditions that suggest that proinflammatory cytokines are one of the main mediators of the disease process. Chronic inflammation is one of the risk factors mentioned for the development of a new cancer; at the same time, it is indicated as an indicator of the worst prognosis. Studies also suggest that the worst prognosis of breast cancer, one of the types with the highest incidence in the world, may be related to increased inflammatory activity. Considering that inflammation is increased in breast cancer and that TENS can reduce proinflammatory cytokines even without blocking the pain pathway, our hypothesis is that the anti-inflammatory effect of TENS can bring benefits to these patients. The aim of this study will be to evaluate the effect of TENS on blood reduction of proinflammatory cytokines in breast cancer patients. μs, and intensity (mA)—maximum tolerated by the patient), and the data will be analyzed in the pre- and postintervention of each patient. The application has a total duration of 30 minutes, and 8 ml of blood will be collected before and after the intervention. Proinflammatory  and anti-inflammatory  cytokines will be analyzed. As a primary endpoint, we will analyze the reduction in blood concentration of proinflammatory cytokines, and as secondary endpoints, we will analyze the size of the effect according to each type of proinflammatory cytokine, describe the effect size of the reduction according to the breast cancer immunohistochemistry, and analyze the effect of TENS on anti-inflammatory cytokines. This study is approved by the Research Ethics Committee  and registered in the Brazilian Clinical Trials (Search text: RBR-10jbwh47). This study will evaluate at least 59 patients, over 18 years of age, diagnosed with breast cancer, but who have not yet started any treatment. All patients will be submitted to TENS intervention (Ibramed, Model Neurodyn III, parameters: VIF—turn on, frequency—2-247 Hz, pulse size—50-500  Used since 1970 as an adjunct therapy to control acute and chronic pain in a lot of medical and surgical conditions, transcutaneous electrical nerve stimulation (TENS) is a noninvasive physiotherapeutic resource that acts to block pain through the central nervous system .After pain is present, there are two mechanisms of action that may be involved: (i) blocking nociception reduces the production of proinflammatory cytokines or (ii) decreasing proinflammatory cytokines that decrease pain intensity –8.It is already known that studies that have observed the relationship between pain and cytokines have found that patients who report less intense pain have less production of proinflammatory cytokines , 10.The mechanism block pain described above was thought of for the hypothesis that the TENS, a physiotherapeutic resource that acts in the path of pain, could reduce cytokines. To answer the question, a systematic review of randomized clinical trials was carried out, and it was found in the meta-analysis that TENS significantly reduced blood proinflammatory cytokines compared to the control group .Analyzing the literature, the authors describe that in addition to the analgesic effect, the electric current has also shown systemic effects, and one of those that is mentioned is the anti-inflammatory effect , 12–15.In the systematic review, we observed that one article evaluated the reduction of cytokines and pain . The othIn the research of Wang et al. , for exaBy analyzing the studies related to chronic disease –19, it wFor testing the effect of TENS on cytokines without block pain, we searched the literature for clinical conditions suggesting that the proinflammatory cytokines are one of the main mediators of the disease process.The chronic inflammatory process can be related to an increased risk to develop cancer, since it implies changes in the tissue microenvironment , 21. ThiWhenever inflammatory cells secrete a variety of factors, including chemokines and cytokines , they fuThe cancer immune system is related to the production of catabolic signals and stimulation of the production of proinflammatory cytokines and growth factors by tumor cells. The increase of Tumor necrosis factor alpha (TNF-α) paired increase of interleukins might be related a worst prognosis in cancer. The chronic inflammation can result in an increased possibility of developing a new cancer .Several types of cancer are studied in the literature, but the relationship between chronic inflammation and cytokines was initially observed in breast cancer , 21, 28.Breast cancer is one of the types with the highest incidence in the world, and because of that, several topics are developed to identify potential risk factors and protection against cancer –31.Considering that inflammation is increased in breast cancer and that TENS can reduce proinflammatory cytokines even without blocking the pain pathway, our hypothesis is that the anti-inflammatory effect of TENS can cause benefit for these patients. The aim of this study will be to evaluate the effect of TENS on blood reduction of proinflammatory cytokines in patients with breast cancer.TENS is a noninvasive, easy-to-apply, and low-cost therapeutic resource. Several studies have pointed out the benefits of TENS in a variety of pathologies, and, so far, no deleterious effects of the use of TENS are known.The main clinical benefit would be that the reduction of proinflammatory cytokines (protective factor against inflammation) could be applied in diseases that have inflammatory causes or inflammatory complications. We could use TENS as a regulator of the inflammatory process.Regarding the research risks, we can mention complications resulting from procedures such as skin irritations and a small cutaneous hematoma during blood collection.A protocol of clinical trials was developed following the guidelines of Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) . The cheThe objective of this study is carried out to assess the reduction of proinflammatory cytokines after TENS application in patients with breast cancer. A nonrandomized, open, single-arm clinical trial with paired analysis will be developed. The study design is described in A minimum of 59 patients is expected. All subjects will receive a single application of TENS for 30 minutes. Assessments will be made before and after application. Screening data will be reviewed to determine subject eligibility. Individuals who meet all of the inclusion criteria and none of the exclusion criteria will be included in the study. The total duration of the subject's participation will be one day .The endpoints for the study are described below:Primary Endpoint. The primary endpoint is to analyze the reduction in blood concentration of proinflammatory cytokines.Secondary Endpoint. The secondary endpoints are to analyze the effect size according to each type of proinflammatory cytokine, describe the effect size of the reduction according to breast cancer immunohistochemistry, and analyze the effect on anti-inflammatory cytokines.Women diagnosed with breast cancer who meet the inclusion and exclusion criteria will be eligible to participate in this study. The eligibility criteria are described in The study will be carried out on the premises of the clinical research site , and these patients will be recruited as they arrive at the site to be evaluated in the protocols.Patients are referred to the research site by doctors and partner hospitals who have already been informed of ongoing breast cancer studies. The research criteria have already been passed to all partners, and as soon as a patient is identified, they are invited to go to the research site where all the information is explained in more detail.The consent form will be obtained as the first procedure from all participants by the study coordinator. The confidentiality of the data will be guaranteed until the end of the research.The study will not be randomized. All patients will be submitted to TENS intervention, and the data will be analyzed in the pre- and postintervention of each patient.Since it is a sensory current, patients will be blinded regarding the modulation of the current , but not for the sensation and intensity that must be perceived during the application. All of the patients will be asked about the tingling perception that the current causes, and the intensity limit will be the maximum sensation that is tolerated.The laboratory technicians will be blinded about the study design and will receive the samples identified by number and the indication of pre and post.A single application will be performed for only 30 minutes on each patient.The area chosen for application will not expose parts of the body and will be easy to apply. To standardize the application, anatomical points will be used as a reference. The location of the placement of the self-adhesive electrodes (5 cm) will be shown in TENS equipment  will be used during the study.The parameters of application of TENS can be adjusted in several ways, but studies have already shown that patients tend to show sensitivity accommodation with a continuous stimulus. Studies that evaluated the decrease in pain compared to control groups obtained better results using the TENS modality with variable intensity and frequency (VIF). These results suggest that it is important to adjust the pulse amplitude during the application of TENS to obtain maximum and longer-lasting analgesic effects when compared to fixed parameter modalities , 34.Regarding the intensity adjustment, a study that evaluated dose response in relation to pain showed that stronger intensities had greater effect. For this reason, it is suggested that the intensity of TENS be applied at the highest possible intensity to obtain maximum pain relief .For the application of the TENS current, the programming is stipulated as described in All procedures will be performed within the premises of Pesquisare Saúde , in the space already equipped and suitable for carrying out international clinical research, and the analysis of blood will be made by the Clinical Analysis Laboratory of the Centro Universitário FMABC (Brazil).On the day of treatment (D1), after signing the informed consent form (ICF), women will complete an evaluation questionnaire with sociodemographic information, medical history, behavioral habit history, and history of breast cancer . The questionnaire is described in Supplementary Material α), and TNF alpha (TNF-α) and the anti-inflammatory cytokines interleukin 4 (IL-4), interleukin 4 (IL-10), interleukin 13 (IL-13), and transforming growth factor β (FTCβ).The blood will be collected and sent to the clinical laboratory. The study's dependent variables will be the proinflammatory cytokines interleukin 7 (IL-7), interleukin 6 (IL-6), interleukin 2 (IL-2), interleukin 1 . After collection, the samples will be sent on the same day, at room temperature, to the Clinical Analysis Laboratory of the Centro Universitário FMABC .Quantitative analysis of serum levels of proinflammatory cytokines will be performed using the enzyme-linked immunosorbent assay (ELISA) technique , following the manufacturer's guidelines and adopting the instructions in the manual as a reference value.The sample size was based on the calculation of the sample size in pilot studies proposed by Viechtbauer et al. : 5% probp ≥ 0.05) will be presented as means, standard deviations, and 95% confidence intervals, while those that do not present normal distribution according to the Shapiro-Wilk test (p < 0.05) will be presented as medians and respective 95% confidence intervals and 25th and 75% percentiles.For the characterization of the sample, a descriptive analysis of the data will be performed; therefore, the qualitative variables will be described by absolute and relative frequency; the quantitative variables that present normal distribution according to the Shapiro-Wilk test  version 11.0®.RBR-10jbwh47).The study was approved by the Independent Ethics Committee  and is also registered in the Brazilian Clinical Trials ), according to resolution 466/2012 of the National Health Council. The present project has been already approved by the Ethics Research Committee.TENS acts on afferent nerve fibers blocking the nerve transmission of pain—an effect known as gate theory —or stimuRegarding studies with TENS and pain reduction –5, the rIn order to test this hypothesis of the pain blockade (TENS)/cytokine pathway, we developed a systematic review with meta-analysis . The effThe researches indicate that acupuncture or electroacupuncture facilitates the release of certain neurotransmitters, especially opioids . The samα, IL-1, and IL-6 [As opioid receptors are also present on immune cells, TENS-induced opioid release could directly modulate these cells (neuroimmune interaction) . The actand IL-6 .The systemic inhibition of immunity via parasympathetic flow is the path that would explain the anti-inflammatory effect of several nonpharmaceutical modalities  . We hypoRecent research indicates that the neoplasic environment arises from sites of infection, chronic irritation, and inflammation and that inflammation is a component of tumor progression. Coussens and Werb, cited by Kavoussi and Ross , report The primary objective of this protocol is to assess whether TENS can reduce proinflammatory cytokines in an inflammatory disease. Cancer was chosen as the study pathology, considering that studies describe that the chronic inflammation present in the tumor microenvironment increases the risk of developing or disseminating cancer –23. AmonOur hypothesis is that if we have a successful conclusion of the proposed clinical trial, we will identify this anti-inflammatory effect on TENS possibly related to a parasympathetic nerve pathway. We pretend to explore the results and calculate the sample size for other clinical trials that can test and increase the power of evidence of TENS (anti-inflammatory effect) in the treatment of inflammatory diseases.


ObjectivesThere is limited evidence on the infants' postoperative complications who have undergone surgical repair of duodenal atresia and stenosis. This study aimed to identify the factors associated with poor surgical outcomes after the initial repair.MethodsWe retrospectively reviewed the data of 82 patients who underwent surgery for duodenal atresia and stenosis between January 1994 and December 2013 at our institution. Gestational age, birth weight, fetal growth, and other associated anomalies were recorded. Multivariate regression analyses were used to identify the factors associated with surgical outcomes, including postoperative complications and time to full oral intake.ResultsThe median gestational age was 37.6 weeks, with 30 (37%) preterm (<37 weeks) and 11 (13%) early preterm (<34 weeks) infants. The median birth weight was 2531 g, with 27 (33%) patients < 2000 g and 10 (12%) patients < 1500 g. Postoperative surgical complications were identified in 18 (22%) cases, of which 12 (15%) required additional operations. Multivariate regression analysis revealed that a combination of very low birth weight (<1500 g) and early preterm was significantly associated with both surgical and non-surgical postoperative complications  and a prolonged time to full oral intake postoperatively (p = 0.013).ConclusionVery low birth weight and early preterm were significantly associated with postoperative complications and a prolonged time to full oral intake. Congenital duodenal atresia and stenosis are common causes of congenital intestinal obstruction. Surgical treatment for duodenal atresia and stenosis is usually performed during the neonatal period. The survival rate of patients who undergo surgical treatment for duodenal atresia and stenosis has remarkably improved from 45% to 96% over the last 50 years due to improvements in diagnosis, neonatal intensive care, and surgical management .Previous studies on patients who had undergone surgical treatment for esophageal atresia and congenital heart disease have reported that postoperative complications and mortality are associated more with a low birth weight than with normal birth weight -6. OtherPatient selection and data collectionA total of 89 patients underwent surgical treatment for duodenal atresia and stenosis between 1994 and 2013 at Osaka Women’s and Children’s Hospital, Izumi, Japan. After excluding seven patients who underwent laparoscopic surgery, the medical records of the remaining 82 patients were reviewed to retrospectively collect the following clinical data: estimated gestational age (GA), birth weight, antenatal diagnosis, sex, age at the initial operation, clinical presentation , surgical approach, postoperative complications, and death within 90 days.Primary and secondary outcome measuresThe primary outcome measures were complications and deaths within 30 and 90 postoperative days, respectively. All postoperative complications were stratified as being either surgical or non-surgical and were graded I, II, IIIa, IIIb, IVa, IVb, or V according to the Clavien-Dindo classification system . RespiraThe secondary outcome measures for poor surgical outcomes included delays in full oral intake and the length of hospital stay postoperatively. The length of hospital stay was adjusted by subtracting the number of days from a GA of 37 weeks and zero days to eliminate the potential influence of a lower GA.Variables that were analyzed as potential risk factors for the above outcomes included sex, estimated GA, birth weight (BW), chromosomal abnormalities, other associated anomalies, fetal growth , operative time, bleeding, and postoperative morbidities.DefinitionsVery low birth weight was defined as birth weight < 1500 g. The term, preterm, and early preterm were defined as GA ≥ 37 weeks, 34-37 weeks, and <34 weeks, respectively. Fetal growth was categorized into three groups: SGA, AGA, and LGA. SGA and LGA were defined according to the Japanese neonatal anthropometric charts for GA at birth as birth weight below the 10th percentile and that above the 90th percentile, respectively .Statistical analysesContinuous variables were expressed as medians with ranges. Logistic regression analysis was used to assess the association of each factor with postoperative complications, which were expressed as the odds ratio (OR) with a 95% confidence interval (CI). Multicollinearity was assessed by multivariate logistic regression. Due to the significant multicollinearity in the statistical analyses and the significant overlap between very low birth weight and early preterm patients , we combined these two variables for further statistical analyses. Time to full oral intake and the length of postoperative hospital stay were analyzed using the Kaplan-Meier method and the log-rank test. A Cox proportional-hazards model was used to identify the association of each factor with secondary outcomes, which were expressed as the hazard ratio (HR) with a 95% CI. All analyses were performed using the JMP Pro software, version 15.0 . Values of P < 0.05 were considered statistically significant.This study was presented at the Pacific Association of Pediatric Surgeons (PAPS) 2015 Annual Meeting and reviewed by our institutional review board at the time, who waived the need for approval due to the retrospective nature of the investigation.The preoperative features of the patients are shown in Table The details of the associated congenital anomalies are presented in Table The surgical outcomes are shown in Table The details of surgical and non-surgical complications that occurred within 30 postoperative days are described in Table The results of the logistic regression analyses to determine factors associated with postoperative complications are presented in Table The results of the multivariate regression analyses to determine factors associated with the secondary outcome measures indicated that the presence of other associated anomalies and a combination of very low birth weight and early preterm were significantly associated with a prolonged time to full oral intake  and compared patient characteristics and outcomes Table . The onlSecond, we divided our patients according to the association with trisomy 21 and compared the patient characteristics and outcomes Table . There wIn this study, we retrospectively analyzed the data collected over 20 years from a single-institution cohort of 82 patients with congenital duodenal atresia and stenosis who were surgically managed during their neonatal period. Our results revealed that a combination of very low birth weight (<1500 g) and early preterm (<34 weeks) was significantly associated with postoperative surgical complications and non-surgical complications; this patient group experienced a high incidence of complications compared to the remaining patient group. The presence of chromosomal abnormalities was also significantly associated with postoperative non-surgical complications.Prior studies have reported that survival after surgical repair of duodenal atresia and stenosis has improved by up to 96% over the last 50 years due to advances in neonatal surgical care ,12. In tSurgeries in premature neonates continue to be a challenge as these patients are at a greater risk of undesirable postoperative outcomes. Preterm or low birth weight neonates usually have immature organ function and are, therefore, highly vulnerable to invasive procedures and stressors . HoweverA retrospective study investigating intestinal atresia, including a duodenal atresia subset, showed that patients with a birth weight < 2000 g and those with associated anomalies were at an increased risk of prolonged hospital stay and mortality . HoweverRegarding secondary outcome measures, the presence of other associated anomalies and a combination of very low birth weight and early preterm were significantly associated with a prolonged time to full oral intake. No significant risk factors were identified for a prolonged hospital stay postoperatively. A previous study reported that delayed oral intake in patients with duodenal atresia and stenosis was significantly associated with GA < 35 weeks, congenital heart disease, and malrotation ; these rA successful surgical approach for duodenal atresia and stenosis in a cohort that is particularly susceptible to postoperative morbidities has not yet been fully established . RecentlOur findings suggest that patients with severe prematurity are at an increased risk of postoperative complications and a prolonged time to full oral intake. Based on our results, we would like to endorse a slightly conservative approach for the management of stable patients with duodenal atresia and stenosis in which a thorough systematic search for any features that may affect their outcomes, along with proactive medical management to stabilize any physiological disturbances, is prioritized before taking a surgical decision. Very low birth weight and early preterm patients with duodenal atresia and stenosis may benefit from being transferred and treated in highly experienced tertiary neonatal centers comprising specialized surgeons and anesthesiologists. In cases where other associated anomalies that require earlier surgical correction - such as complex cardiac anomalies or esophageal atresia/tracheoesophageal fistulas - are present, we suggest that the duodenal obstruction be repaired later. During the initial anomaly intervention, these patients are maintained on parenteral nutrition without adverse liver effects .The limitations of this study include its retrospective nature and its relatively small cohort size. On the other hand, the data from our study population were taken over a 20-year follow-up, in which consistent treatment guidelines (at a single center) were followed. There was no significant difference in patient characteristics and outcomes over the study period, except for the improved antenatal diagnosis in recent years Table . As the In summary, we conducted a retrospective analysis of data from patients who underwent surgical treatment for duodenal atresia and stenosis to identify the predictors of poor postoperative outcomes. Based on our findings, we conclude that early preterm and very low birth weight are associated with a high incidence of postoperative complications and a prolonged time to full oral intake in patients with duodenal atresia and stenosis. Future studies should focus on the risk stratification among a cohort of infants with duodenal atresia and stenosis and optimization of the operative management strategies accordingly to mitigate the surgical risk of susceptible infants.