The Genetic Determinants of Axial Length: From Microphthalmia to High Myopia in Childhood.

The axial length of the eye is critical for normal visual function by enabling light to precisely focus on the retina. The mean axial length of the adult human eye is 23.5 mm, but the molecular mechanisms regulating ocular axial length remain poorly understood. Underdevelopment can lead to microphthalmia (defined as a small eye with an axial length of less than 19 mm at 1 year of age or less than 21 mm in adulthood) within the first trimester of pregnancy. However, continued overgrowth can lead to axial high myopia (an enlarged eye with an axial length of 26.5 mm or more) at any age. Both conditions show high genetic and phenotypic heterogeneity associated with significant visual morbidity worldwide. More than 90 genes can contribute to microphthalmia, and several hundred genes are associated with myopia, yet diagnostic yields are low. Crucially, the genetic pathways underpinning the specification of eye size are only now being discovered, with evidence suggesting that shared molecular pathways regulate under- or overgrowth of the eye. Improving our mechanistic understanding of axial length determination will help better inform us of genotype-phenotype correlations in both microphthalmia and myopia, dissect gene-environment interactions in myopia, and develop postnatal therapies that may influence overall eye growth.

The impact of China's universal two-child policy on total, preterm, and multiple births: a nationwide interrupted time-series analysis.

BACKGROUND: Although years have passed since the implementation of China's universal two-child policy, the effectiveness of this policy remains unclear. To address this knowledge gap, we, here, assessed the impact of the two-child policy on total live births, preterm births, and multiple live births. METHODS: Data identifying pregnancies resulting in at least one live birth between April 1 2013 and December 31 2018 were collected from the Hospital Quality Monitoring System database. Using an interrupted time-series analysis, we estimated immediate level changes and long-term trends in total, preterm (birth before 37 weeks' gestation), and multiple live births that had occurred after July 2016, when the universal two-child policy had taken effect. RESULTS: A total of 8,273,622 live births were reported during the study time frame. The number of live births (p = 0.277), preterm births (p = 0.052), and multiple births (p = 0.856) per month slightly increased immediately after July 2016, but these increases did not meet statistical significance. Further, all three outcomes showed a significant downward trend that lasted until the end of 2018 (p < 0.0001 for all). Among all live births, the percentage of preterm births remained stable (p = 0.101), while the percentage of multiple live births that were preterm significantly increased (trend change = 0.21% per month, 95% CI 0.14 to 0.28, p < 0.0001). The percentage of live multiple births among all live births significantly decreased (p for trend = 0.0039). CONCLUSIONS: Overall, our data reveal a transient baby boom, as well as an increase in the proportion of live multiple births that were preterm, after China's two-child policy took effect. The latter should be noted by healthcare professionals due to the high risk of complications and special medical care required by preterm babies.

The needs of multiple birth families during the first 1001 critical days: A rapid review with a systematic literature search and narrative synthesis.

OBJECTIVE: Supporting families during the first 1001 days from conception to the age of two is vital for setting the emotional, cognitive, and physical building blocks for children's futures. Families with twins, triplets, or higher order multiples (multiple birth families) have unique challenges due to caring for more than one baby at the same time. Therefore, identifying the needs of multiple birth families is necessary to provide optimum support during the first 1001 critical days. DESIGN: A rapid review was undertaken to synthesize knowledge of the needs of multiple birth families in the United Kingdom (UK) during the first 1001 critical days. Findings from five databases (MEDLINE, APA PsycArticles, APA PsycInfo, CINAHL, and Web of Science) for peer-reviewed studies and grey literature published between 2012 and 2022 were synthesized. Fifteen studies were reviewed using narrative synthesis. RESULTS: Multiple birth families have unique and complex emotional and practical needs across the first 1001 critical days, and in particular, the first-year post birth, impacted further by complicated pregnancies and prematurity. Needs were identified within the four key themes: high risk pregnancy and birth; transformed reality of raising multiples; inadequate support; and positively affecting experiences. Health professional support was inconsistent and particularly lacking in intrapartum, postnatal, and community care including transition. CONCLUSION: Multiple birth families' needs should be considered in the design and delivery of care within the first 1001 critical days, especially within the first year after birth. Multiples specific advice across the first 1001 critical days is needed and training for health professionals to adapt universal advice for this population is one way to achieve this. Further research is needed to ensure this advice is evidence based and effective.

Births: Final Data for 2019.

Objectives-This report presents 2019 data on U.S. births according to a wide variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. Methods-Descriptive tabulations of data reported on the birth certificates of the 3.75 million births that occurred in 2019 are presented. Data are presented for maternal age, livebirth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates by age are also shown. Trend data for 2010 through 2019 are presented for selected items. Trend data by race and Hispanic origin are shown for 2016-2019. Results-A total of 3,747,540 births were registered in the United States in 2019, down 1% from 2018. The general fertility rate declined from 2018 to 58.3 births per 1,000 women aged 15-44 in 2019. The birth rate for females aged 15-19 fell 4% between 2018 and 2019. Birth rates declined for women aged 20-34 and increased for women aged 35-44 for 2018-2019. The total fertility rate declined to 1,706.0 births per 1,000 women in 2019. Birth rates declined for both married and unmarried women from 2018 to 2019. The percentage of women who began prenatal care in the first trimester of pregnancy rose to 77.6% in 2019; the percentage of all women who smoked during pregnancy declined to 6.0%. The cesarean delivery rate decreased to 31.7% in 2019 (Figure 1). Medicaid was the source of payment for 42.1% of all births in 2019. The preterm birth rate rose for the fifth straight year to 10.23% in 2019; the rate of low birthweight was essentially unchanged from 2018 at 8.31%. Twin and triplet and higher-order multiple birth rates both declined in 2019 compared with 2018.

Multiple births and low birth weight: Evidence from South Korea.

OBJECTIVE: The proportion of multiple births has risen rapidly worldwide. Multiple births are likely to affect birth weight, which results in low birth weight (LBW) of less than 2500 g, possibly, because multiples are more likely to be born prematurely or less than 37 weeks into pregnancy. Using data from South Korea, this study aims to estimate the contribution of the rise in multiples to the rise in LBW incidence. METHODS: Based on data from 2000 to 2017, we estimated the effect of multiples on LBW rates using linear regression analysis. Based on the regression analysis and the change in the proportion of multiples during this period, we calculated the contribution of the rise in multiples to the rise in LBW incidence using the total differential. In other words, we divided the change in LBW during the period due to the change in multiples by the total change during the period. The data are from the birth registry of the National Statistical Office, which contains information on the 8.4 million live births during the period 2000-2017. RESULTS: We found that a 1 percentage point increase in multiples increases the proportion of LBWs by 0.495 percentage points. In addition, because the changes in the proportion of multiples and LBWs from 2000 to 2017 are 2.2 and 2.4 percentage points, respectively, 1.1 percentage points or 45.8% of the increase in LBWs over the period is due to the increase in multiples. CONCLUSION: Since the Korean government introduced a measure to reduce the number of transferred embryos recently, one may expect that multiples in Korea would reduce in the near future, as it did in other countries. Subsequently, the incidence of LBW children is also likely to reduce, which is desirable in terms of the children's health outcomes.

Associated regions for multiple birth in Brown Swiss and Original Braunvieh cattle on chromosomes 15 and 11.

Twin and multiple births have negative effects on the performance and health of cows and calves. To decipher the genetic architecture of this trait in the two Swiss Brown Swiss cattle populations, we performed various association analyses based on de-regressed breeding values. Genome-wide association analyses were executed using ~600 K imputed SNPs for the maternal multiple birth trait in ~3500 Original Braunvieh and ~7800 Brown Swiss animals. Significantly associated QTL were observed on different chromosomes for both breeds. We have identified on chromosome 11 a QTL that explains ~6% of the total genetic variance of the maternal multiple birth trait in Original Braunvieh. For the Brown Swiss breed, we have discovered a QTL on chromosome 15 that accounts for ~4% of the total genetic variance. For Original Braunvieh, subsequent haplotype analysis revealed a 90-kb window on chromosome 11 at 88 Mb, where a likely regulatory region is located close to the ID2 gene. In Brown Swiss, a 130-kb window at 75 Mb on chromosome 15 was identified. Analysis of whole-genome sequence data using linkage-disequilibrium estimation revealed possible causal variants for the identified QTL. A presumably regulatory variant in the non-coding 5' region of the ID2 gene was strongly associated with the haplotype for Original Braunvieh. In Brown Swiss, an intron variant in PRDM11, one 3' UTR variant in SYT13 and three intergenic variants 5' upstream of SYT13 were identified as candidate variants for the trait multiple birth maternal. In this study, we report for the first time QTL for the trait of multiple births in Original Braunvieh and Brown Swiss cattle. Moreover, our findings are another step towards a better understanding of the complex genetic architecture of this polygenic trait.

Under age five children survival times in Nigeria: a Bayesian spatial modeling approach.

BACKGROUND: Nigeria is among the top five countries in the world with the highest under-five mortality rates. In addition to the general leading causes of under-five mortality, studies have shown that disparity in sociocultural values and practices across ethnic groups in Nigeria influence child survival, thus there is a need for scientific validation. This study quantified the survival probabilities and the impact of socioeconomic and demographic factors, proximate and biological determinants, and environmental factors on the risk of under-five mortality in Nigeria. METHODS: The Kaplan-Meier survival curve, Nelson Aalen hazard curve, and components survival probabilities were estimated. The Exponential, Gamma, Log-normal, Weibull, and Cox hazard models in a Bayesian mixed effect hierarchical hazard modeling framework with spatial components were considered, and the Deviance and Watanabe Akaike information criteria were used to select the best model for inference. A [Formula: see text] level of significance was assumed throughout this work. The 2018 Nigeria Demographic and Health Survey dataset was used, and the outcome variable was the time between birth and death or birth and the date of interview for children who were alive on the day of the interview. RESULTS: Findings show that the probability of a child dying within the first two months is 0.04, and the probability of a boy child dying before attaining age five is 0.106, while a girl child is 0.094 probability. Gender, maternal education, household wealth status, source of water and toilet facility, residence, mass media, frequency of antenatal and postnatal visits, marital status, place of delivery, multiple births, who decide healthcare use, use of bednet are significant risk factors of child mortality in Nigeria. The mortality risk is high among the maternal age group below 24 and above 44years, and birth weight below 2.5Kg and above 4.5Kg. The under-five mortality risk is severe in Kebbi, Kaduna, Jigawa, Adamawa, Gombe, Kano, Kogi, Nasarawa, Plateau, and Sokoto states in Nigeria. CONCLUSION: This study accentuates the need for special attention for the first two months after childbirth as it is the age group with the highest expected mortality. A practicable way to minimize death in the early life of children is to improve maternal healthcare service, promote maternal education, encourage delivery in healthcare facilities, positive parental attitude to support multiple births, poverty alleviation programs for the less privileged, and a prioritized intervention to Northern Nigeria.

Single Center Outcome of Multiple Births in the Premature and Very Low Birth Weight Cohort in Singapore.

OBJECTIVE: The aim of this study is to compare neonatal mortality and morbidity in multiple and singleton preterm/very low birthweight (PT/VLBW) multiethnic Asian infants. STUDY DESIGN: Cohort study of 676 singleton and 299 multiple PT/VLBW infants born between 2008 and 2012 at KK Women's and Children's Hospital, the largest tertiary perinatal center in Singapore with further stratification by gestational ages 23 to 25 (Group 1), 26 to 28 (Group 2), and ≥29 (Group 3) weeks. Outcome measures included predischarge mortality and major neonatal morbidity. RESULTS: Overall survival to discharge was comparable for singletons 611/676 (90%) and multiples 273/299 (91%). Use of assisted reproductive technologies (47 vs. 4%), antenatal steroids (80 vs. 68%), and delivery by cesarean section (84 vs. 62%) were significantly higher (p < 0.001) in multiples while pregnancy induced hypertension (8.7 vs. 31.6%, p < 0.001) and maternal chorioamnionitis (31 vs. 41%, p < 0.01) were seen less commonly compared with singleton pregnancies. Survival was comparable between singletons and multiples except for a lower survival in multiples in Group 2 (81.7 vs. 92.4%, p = 0.007). Major neonatal morbidities were comparable for multiples and singletons in the overall cohort. Presence of hemodynamically significant patent ductus arteriosus (HsPDA) requiring treatment (88.9 vs. 72.5%), air leaks (33 vs. 14.6%, p = 0.02), NEC (30 vs. 14.6%, p = 0.04), and composite morbidity (86 vs. 66%, p = 0.031) were significantly higher in multiples in Group 1. A significantly higher incidence of HsPDA (68.1 vs. 52.4%, p = 0.008) was also observed in multiples in Group 2. Multiple pregnancy was not an independent predictor of an adverse outcome on regression analysis (OR: 0.685, 95% confidence interval: 0.629-2.02) even in GA ≤25 weeks. CONCLUSION: Neonatal mortality and morbidity were comparable in our cohort of PT/VLBW singletons and multiple births, but preterm multiple births ≤25 weeks had a higher incidence of neonatal morbidity. KEY POINTS: · Use of assisted reproductive technologies was significantly higher in multiples as compared to singletons.. · Major neonatal morbidities and mortality were similar between singletons and multiples in our cohort.. · In gestations less than 25 weeks multiples had higher neonatal morbidities than their singleton counterparts..

Supporting multiple birth families: Perceptions and experiences of health visitors.

OBJECTIVE: To explore the current practice and perceptions of health visitors in supporting multiple birth families. DESIGN AND SAMPLE: Practicing health visitors across the United Kingdom were invited to complete a cross-sectional, descriptive, online survey. The questionnaire covered multiple birth caseload, education received about multiples and the experience of working with families. Two-hundred and ninety health visitors completed the questionnaire. Descriptive and inferential statistics were used for analysis of the quantitative components and thematic analysis for the qualitative data. RESULTS: Most health visitors had twins on their current workload. Most health visitors had not received any specific training or continuing professional development regarding the needs of multiple birth families. Supporting the families within the confines of reduced time and increased workload was challenging. Daily tasks of caring for multiples were the main areas that health visitors and parents wanted more information about. CONCLUSIONS: In the United Kingdom, health visitors are uniquely positioned to support multiple birth families, in particular during the more challenging early years. However, the findings of this study suggest that many health visitors are aware that the care and support that they are able to provide multiple birth families falls short of meeting their needs.

Birth characteristics and childhood leukemia in Switzerland: a register-based case-control study.

PURPOSE: Initial genetic alterations in the development of childhood leukemia occur in utero or before conception; both genetic and environmental factors are suspected to play a role. We aimed to investigate the associations between childhood leukemia and perinatal characteristics including birth order, birth interval to older siblings, parental age, birth weight, and multiple birth. METHODS: We identified cases diagnosed between 1981 and 2015 and born in Switzerland between 1969 and 2015 from the Swiss Childhood Cancer Registry and randomly sampled five controls per case from national birth records matched on date of birth, sex, and municipality of residence at birth. We used conditional logistic regression to investigate associations between perinatal characteristics and leukemia at ages 0-15 and 0-4 years, and the subtypes acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). RESULTS: The study included 1,403 cases of leukemia. We observed increased risks associated with high birth weight (adjusted OR 1.37, 95% CI 1.12-1.69) and multiple birth (1.89, 1.24-2.86). These associations were similar for ALL and stronger for leukemia at ages 0-4 years. For AML, we observed an increased risk for higher birth order (3.08, 0.43-22.03 for fourth or later born children). We found no associations with other perinatal characteristics. CONCLUSION: This register-based case-control study adds to the existing evidence of a positive association between high birth weight and risk of childhood leukemia. Furthermore, it suggests children from multiple births are at an increased risk of leukemia.

Outcomes of Infants with Very Low Birth Weight Associated with Birthplace Difference: A Retrospective Cohort Study of Births in Japan and California.

OBJECTIVE: To determine whether outcomes among infants with very low birth weight (VLBW) vary according to the birthplace (Japan or California) controlling for maternal ethnicity. STUDY DESIGN: Severe intraventricular hemorrhage (IVH) and mortality were ascertained for infants with VLBW born at 24-29 weeks of gestation during 2008-2017 and retrospectively analyzed by the country of birth for mothers and infants (Japan or California). RESULTS: Rates of severe IVH, mortality, or combined IVH/mortality were lower in the 24 095 infants born in Japan (5.1%, 5.0%, 8.8% respectively) compared with infants born in California either to 157 mothers with Japanese ethnicity (12.5%, 9.7%, 17.8%) or to a comparison group of 6173 non-Hispanic white mothers (8.4%, 8.8%, 14.6%). ORs for adverse outcomes were increased for infants born in California to mothers with Japanese ethnicity compared with infants born in Japan for severe IVH (OR, 3.31; 95% CI, 1.93-5.68), mortality (3.73; 95% CI, 2.03-6.86), and the combined outcome (3.26; 95% CI, 2.02-5.27). The odds of these outcomes also were increased for infants born in California to non-Hispanic white mothers compared with infants born in Japan. Outcomes of infants born in California did not differ by Japanese or non-Hispanic white maternal ethnicity. CONCLUSIONS: Low rates of severe IVH and mortality for infants with VLBW born in Japan were not seen in infants born in California to mothers with Japanese ethnicity. Differences in systems of regional perinatal care, social environment, and the quality of perinatal care may partially account for these differences in outcomes.

Births: Final Data for 2018.

Objectives-This report presents 2018 data on U.S. births according to a wide variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. Methods-Descriptive tabulations of data reported on the birth certificates of the 3.79 million births that occurred in 2018 are presented. Data are presented for maternal age, live-birth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates by age also are shown. Trend data for 2010 through 2018 are presented for selected items. Trend data by race and Hispanic origin are shown for 2016-2018. Results-3,791,712 births were registered in the United States in 2018, down 2% from 2017. Compared with rates in 2017, the general fertility rate declined to 59.1 births per 1,000 women aged 15-44. The birth rate for females aged 15-19 fell 7% in 2018. Birth rates declined for women aged 20-34 and increased for women aged 35-44. The total fertility rate declined to 1,729.5 births per 1,000 women in 2018. Birth rates for both married and unmarried women declined from 2017 to 2018. The percentage of women who began prenatal care in the first trimester of pregnancy rose to 77.5% in 2018; the percentage of all women who smoked during pregnancy declined to 6.5%. The cesarean delivery rate decreased to 31.9% in 2018 following an increase in 2017. Medicaid was the source of payment for 42.3% of all 2018 births, down 2% from 2017. The preterm birth rate rose for the fourth straight year to 10.02% in 2018; the rate of low birthweight was unchanged at 8.28%. Twin and triplet and higher-order multiple birth rates declined in 2018 (Figure 1).

Celebrating 30 years of ART in Latin America; and the 2018 report.

RESEARCH QUESTION: What are the trends in patient characteristics, effectiveness and safety of assisted reproductive technology (ART) performed in Latin America over the past three decades, as well as the detailed outcomes of procedures initiated in 2018? DESIGN: Retrospective collection of multinational data including epidemiology and outcomes of ART performed between 1990 and 2018. RESULTS: Over these 30 years we report 955,117 initiated cycles, 191,191 deliveries and 238,045 live births. In 1990, 66.5% of women were ≤34 years and 8.7% ≥40 years; in 2018, 26.4% of women were ≤34 years and 32.0% were ≥40 years. In 1990, 60.4% of transfers included ≥3 embryos, falling to 13.5% in 2018, and single embryo transfer (SET) increased from 13.8% to 30.4% between 1990 and 2018. Delivery rate per fresh transfer increased from approximately 17% in the 1990s to 25% in 2018, with a meaningful drop in high-order multiples, from 5-9% in the 1990s to 0.4% in 2018. This drop is associated with increasing use of frozen embryo transfer (FET) (57% in 2018) compared with 10% in 2000. In 2018, delivery rate in FET was 28.3%, reaching 31.2% in freeze-all cycles; and the cumulative live birth rate (fresh + FET) was 41.9%. Elective SET also increased, from 0.9% in 2010 to 10% in 2018. The delivery rate in elective SET (31.7%) was only 5.4% lower than elective double embryo transfer (DET) (37.1%); however, multiple births increased from 2.1% to 25.5% twins and 0.4% triplets in elective DET. CONCLUSION: The Latin American Registry of Assisted Reproduction (RLA) celebrates 30 years of voluntary reporting from a total of nearly 200 centres in 15 countries. This South-South Cooperation network has proven to be an efficient and safe system for technological transfer and regional growth.

Cerebral palsy in twins and higher multiple births: a Europe-Australia population-based study.

AIM: To describe the birth prevalence, temporal trends, and clinical outcomes of twins, triplets, or quadruplets with cerebral palsy (CP). METHOD: This was a cross-sectional study using data for twins, triplets, and quadruplets with prenatally or perinatally acquired CP and pooled from the Surveillance of Cerebral Palsy in Europe network (born 1992-2009) and Australian Cerebral Palsy Register (born 1993-2009). Children were at least 4 years old at time of registration. Children born in regions with population ascertainment and available denominator data were included in prevalence calculations (n=1033 twins, 81 triplets, and 11 quadruplets). Clinical data from children registered in all participating registers were described, including 2163 twins (56% male), 187 triplets (59% male), and 20 quadruplets (45% male). RESULTS: The birth prevalence of CP was higher with increasing plurality (twins 6.5 per 1000 live births [95% confidence interval {CI} 6.1-6.9], triplets 17.1 [95% CI 13.6-21.2], quadruplets 50.7 [95% CI 25.6-88.9]); however, prevalence by gestational age was similar across all pluralities. Between 1992-1994 and 2007-2009, prevalence of CP among twins declined (p=0.001) but prevalence of CP among triplets did not change significantly over time (p=0.55). The distributions of Gross Motor Function Classification System, epilepsy, and impairments of intellect, vision, and hearing were similar regardless of plurality. INTERPRETATION: The data combined from two CP register networks indicated that triplets and quadruplets had increased risk of CP compared to twins. The higher prevalence of CP in triplets and quadruplets is due to their higher risk of preterm birth. Prevalence of CP among twins significantly declined in Europe and Australia. Clinical outcomes were similar for all multiple births.

Survival and early complications of preterm infants with birthweight less than 500 grams during a 10-year period in Hungary.

BACKGROUND: There are limited data available on the survival and early complications of preterm infants with less than 500 g birthweight. To estimate the outcomes for these infants, it is important for caregivers to be aware of perinatal factors that may affect survival. OBJECTIVES: We assessed the mortality and certain early complications of preterm infants born with less than 500 g in Hungary between 2006 and 2015. METHODS: We reviewed data of 486 infants from the database of the Hungarian Central Statistical Office and in parallel of 407 infants from the "NICU database." The study period was divided into two epochs: 2006-2010 and 2011-2015. RESULTS: The survival was 27.1% in the first epoch and 39.1% in the second epoch, and the incidence of early complications was slightly higher in the second epoch. In the surviving group (first and second epoch combined), gestational age (25.1 vs 23.7 weeks), birthweight (458 vs 447 g) antenatal steroid treatment (66.3% vs 52.3%), surfactant therapy (95.1% vs 84.3%), median Apgar scores (6 vs 3 and 8 vs 5 at 1 and 5 minutes, respectively) and proportion of caesarean delivery (89.3% versus 68.5%) were higher than in the non-surviving group (first and second epoch combined). The proportion of multiple births was lower in the surviving group (15.7% vs 33.4%). CONCLUSIONS: Survival of infants with less than 500 g improved between 2006-2010 and 2011-2015 in Hungary. The slightly higher occurrence of early complications might be associated with improving survival.

Naturally monozygotic quadruplets in a Braford cow confirmed by DNA analysis: A case report.

Cattle are a monotocous species, despite naturally conceived multiple births are sometimes observed. Although the number of twins has consistently increased, triplet and quadruplet pregnancies represent 0.015% and 0.004% of the total births, respectively. Multiple births are the result of multiple ovulation and/or the spontaneous cleavage of one fertilized oocyte, which is known as monozygotic (MZ) twinning. In cattle, approximately 5% to 14% of all twin births are MZ, and births with more than two MZ calves are extremely rare. Monozygotic animals are genetically identical, and those derived from two or more zygotes are genetically different. Furthermore, the presence of placental vascular anastomosis can result in foetal chimerism. Notwithstanding, animals born as single calves can be chimeras when one of the foetal twins dies undetected in utero. Here, we used DNA testing to study the zygotic condition of an unusual female quadruplet born from a Braford cow bred in a multi-sire natural mating system without hormone stimulation. Two tissues with different embryological origin were sampled to test zygosity and possible chimerism. The results showed an identical genotype, confirming they all originated in an MZ pregnancy and suggesting the lack of chimerism in all animals. The use of MZ twins in breeding and selection systems provides an alternative to the conventional progeny testing. Some works have suggested a genetic background of MZ twins in humans. This female and her daughters could be the founders of a lineage to study the possible inheritance of MZ multiple births in cattle.

The New West Japan Twins and Higher Order Multiple Births Registry.

The new West Japan Twins and Higher Order Multiple Births Registry was established by recruiting young twins and multiple births and by referrals from public health centers in the 1990s. The participants included in the survey comprised over 7800 twins and 4241 higher order multiples, and their families. Specifically, the present registry contains one of the largest triplet samples in the world. For these twins and multiples, data on year of delivery, mode of delivery, gestational age, intrapartum complications, longitudinal physical measures, motor milestones, cerebral palsy and feeding methods were obtained from records in the Maternal and Child Health Handbooks and schools. Participating mothers were asked to indicate family structure, parental educational history, maternal sleeping time, maternal health condition, maternal and paternal age at multiple delivery, complications during pregnancy, handedness of multiples and age at menarche of multiples. However, the zygosity differed among the various collaborating public health centers according to factors such as the time of investigation. Follow-up questionnaires have been mailed out every 3-4 years for longitudinal studies. This article describes the goals of this registry, recruitment of multiples and the focus of the study. The goals of this registry are not only to conduct research on human genetics and maternal and child health, but also to contribute to providing appropriate information for families with multiples.

Database of Families with Twins and Higher Order Multiples in Japanese Twins Mothers Clubs.

It is desirable for twin researchers to be aware of the needs and concerns of families of multiples and provide participants with appropriate and useful feedback and advice based on scientific evidence. Our most recent database on families with twins throughout Japan is based on a questionnaire survey conducted in 2016. Mailed questionnaires, consisting of over 500 items, were used to collect the basic data. The response rate was 38% (566/1478). This is part of a nationwide study designed to assess the long-term effect of perinatal conditions on mothers of multiples. Its aim was to study the growth and development of multiples in childhood, and for the creation of a multifetal mother and child health handbook, and to conduct a genetic epidemiologic study to test the developmental origin of health and disease hypothesis. One of the ultimate aims of this research was to provide evidence-based information on parenting of multiples for families with multiples.

The East Flanders Prospective Twin Survey (EFPTS): 55 Years Later.

The East Flanders Prospective Twin Survey (EFPTS) is a registry of multiple births in the province of East Flanders, Belgium. Since its start in 1964, over 10,000 twin-pairs have been registered. EFPTS has several unique features: it is population-based and prospective, with the possibility of long-term follow-up; the twins (and higher order multiple births) are recruited at birth; basic perinatal data are recorded; chorion type and zygosity are established; since 1969, placental biopsies have been taken and frozen at -20°C for future research. Since its origin, the EFPTS has included placental data and allows differentiation of three subtypes of monozygotic twins based on the time of the initial zygotic division: the dichorionic-diamniotic pairs (early, with splitting before the fourth day after fertilization), the monochorionic-diamniotic pairs (intermediate, splitting between the fourth- and the seventh-day postfertilization) and the monochorionic-monoamniotic pairs (late, splitting after the eighth day postfertilization). Studies can be initiated taking into account primary biases, those originating 'in utero'. Such studies could throw new light on the consequences of early embryological events and the gene-environment interactions as far as periconceptional and intrauterine environment are concerned.

Breast Milk for Preterm Multiples: More Proteins, Less Lactose.

Exclusive breastfeeding is currently recommended until at least 6 months of postnatal age, due to maternal breast milk (BM) unique composition and beneficial properties. In fact, BM modifies itself according to gestational age (GA) at birth, adapting its composition to neonatal requests during lactation. Multiple births represent about 3% of the whole pregnancies; such neonates result more vulnerable than full-term newborns, due to lower GA and birth weight (BW) and the higher incidence of perinatal complications. Although an adequate nutrition is fundamental for twins and other multiples, studies on this topic are lacking. We collected and analyzed BM from mothers of 19 twins and 5 triplets showing GA < 33 weeks and BW < 1500 g, comparing it to a control group of 28 preterm singletons. As a result, at GA ≤ 28 weeks, we observed that protein content is higher in BM for multiples (1.53 vs. 1.29 g per 100 ml), lactose concentration is greater in BM for singletons (6.72 vs. 6.34 g per 100 ml) and GA results the most relevant factor influencing BM protein composition. BM for multiples results higher in proteins and lower in lactose, if compared with singleton's samples; this could promote and sustain growth and organ development in this vulnerable category. BM from multiples shows a trophic and immunologic role, since these neonates often show lower GA and BW instead of singletons. These findings could help in optimizing nutritional strategies and improving BM individualized fortification.