[Prenatal diagnosis of fetal microdeletion and microduplication syndromes among pregnant women with advanced maternal ages].

OBJECTIVE: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes. METHODS: A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children's Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out. RESULTS: CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%). CONCLUSION: The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.

Births: Final Data for 2022.

Objectives- This report presents 2022 data on U.S. births by selected characteristics. Trends in fertility patterns and maternal and infant characteristics are described. Methods-Descriptive tabulations based on birth certificates of the 3.67 million births registered in 2022 are shown by 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 also are shown. Trends for 2010 to 2022 are presented for selected items, and by race and Hispanic origin for 2016-2022. Results-A total of 3,667,758 births occurred in the United States in 2022, essentially unchanged from 2021. The general fertility rate declined 1% from 2021 to 56.0 births per 1,000 females ages 15-44 in 2022. The birth rate for females ages 15-19 declined 2% from 2021 to 2022; birth rates fell 7% for women ages 20-24, rose 1% to 5% for women ages 25-29 and 35-44, and rose 12% for women ages 45-49 (the first increase since 2016). The total fertility rate declined less than 1% to 1,656.5 births per 1,000 women in 2022. Birth rates declined for unmarried women but increased for married women from 2021 to 2022. Prenatal care beginning in the first trimester declined to 77.0% in 2022; the percentage of women who smoked during pregnancy declined to 3.7%. The cesarean delivery rate was unchanged in 2022 (32.1%); Medicaid was the source of payment for 41.3% of births. The preterm birth rate declined 1% to 10.38%; the low birthweight rate rose 1% to 8.60%. The twin birth rate was unchanged in 2022 (31.2 per 1,000 births); the 2% decrease in the triplet and higher-order multiple birth rate.

Effect of maternal age on ATP content and distribution of mitochondria in bovine oocytes.

Our objective was to understand how maternal age influences the mitochondrial population and ATP content of in vivo matured bovine oocytes. We hypothesized that in vivo matured oocytes from older cows would have altered mitochondrial number and distribution patterns and lower cytoplasmic ATP content compared to the oocytes obtained from younger cows. Follicles ≥5mm were ablated in old cows (13 to 22 yrs, Old Group, n = 7) and their younger daughters (4 to 10 years old, Young Group; n = 7) to induce the emergence of a new follicular wave. Cows were treated twice daily with eight doses of FSH starting 24 hr after ablation (Day 0, day of wave emergence). Prostaglandin F2alpha (PGF) was given on Days 3 and 3.5, LH on Day 4.5, and cumulus-oocyte-complexes were collected 18-20 hours post-LH by ultrasound-guided follicular aspiration. Oocytes were either processed for staining with MitoTracker Deep Red FM or for ATP assay. Stained oocytes were imaged with a Zeiss LSM 710 confocal microscope, and mitochondria were segmented in the oocyte volume sets using Imaris Pro 7.4. In vivo matured oocytes obtained from old cows were similar in morphological grades to those from young cows. However, the oocytes of COC from older cows had 23% less intracellular ATP (27.4±1.9 vs 35.7±2.2 pmol per oocyte, P = 0.01) than those of young cows. Furthermore, the average volume of individual mitochondria, indicated by the number of image voxels, was greater (P<0.05) in oocytes from older cows than in those from younger cows. Oocytes from older cows also tended to have a greater number of mitochondrial clusters (P = 0.06) and an increased number of clusters in the central region of the oocytes (P = 0.04) compared to those from younger cows. In conclusion, our study demonstrated that maternal age was associated with a decrease in the cytoplasmic ATP content of in vivo mature oocytes and an altered distribution of mitochondrial structures. These findings suggest that maternal age may negatively influence the developmental competence of oocytes from older cows.

[Factors associated with breastfeeding at birth in maternity hospitals linked to the Rede Cegonha, Brazil, 2016-2017]. / Fatores associados ao aleitamento materno ao nascer em maternidades vinculadas à Rede Cegonha, Brasil, 2016-2017.

Breastfeeding (BF) is a human right, and it must start from birth. The adequacy of Rede Cegonha (RC) strategies can contribute to the promotion of BF. The objective was to identify factors associated with BF in the first and 24 hours of live births at full-term maternity hospitals linked to CR. Cross-sectional study with data from the second evaluation cycle 2016-2017 of the RC that covered all of Brazil. Odds ratios were obtained through binary logistic regression according to a hierarchical model, with 95% confidence intervals and p-value < 0.01. The prevalence of BF in the first hour was 31% and in the 24 hours 96.6%. The chances of BF in the first hour increased: presence of a companion during hospitalization, skin-to-skin contact, vaginal delivery, delivery assistance by a nurse and accreditation of the unit in the Baby-Friendly Hospital Initiative. Similar results at 24 hours, and association with maternal age below 20 years. BF in the first hour was less satisfactory than in the 24 hours, probably due to the high prevalence of cesarean sections, a factor associated with a lower chance of early BF. Continuous training of professionals about BF and the presence of an obstetric nurse during childbirth are recommended to expand BF in the first hour.

O aleitamento materno (AM) é um direito humano e deve ser iniciado desde o nascimento. A adequação das estratégias da Rede Cegonha (RC) pode contribuir na promoção do AM. O objetivo foi identificar os fatores associados ao AM na primeira e nas 24 horas de nascidos vivos a termo em maternidades vinculadas à RC. Estudo transversal com dados do segundo ciclo avaliativo 2016-2017 da RC, que abrangeu todo o Brasil. Foram obtidas razões de chance por meio de regressão logística binária segundo modelo hierarquizado, com intervalos de confiança a 95% e p-valor < 0,01. A prevalência de AM na primeira hora foi de 31%, e nas 24 horas, de 96,6%. Aumentaram as chances de AM na primeira hora: presença de acompanhante na internação, contato pele a pele, parto vaginal, assistência ao parto por enfermeira e acreditação da unidade na Iniciativa Hospital Amigo da Criança. Resultados semelhantes nas 24 horas, e associação com idade materna inferior a 20 anos. O AM na primeira hora foi menos satisfatório do que nas 24h, provavelmente pela elevada prevalência de cesariana, fator associado à menor chance de AM precoce. A capacitação dos profissionais sobre AM de forma contínua e a presença de enfermeiro obstetra no parto são recomendadas para ampliar o AM na primeira hora.

Analysis of Down syndrome newborn outcomes in three neonatal intensive care units in Rio de Janeiro, Brazil.

OBJECTIVE: The aim of this study was to analyze the outcomes of newborns with Down syndrome admitted to three neonatal intensive care units in the city of Rio de Janeiro, Brazil. METHODS: A retrospective cohort study was conducted by analyzing the medical records between 2014 and 2018 of newborns with Down syndrome admitted to three neonatal intensive care units. The following variables were analyzed: maternal and perinatal data, neonatal malformations, neonatal intensive care unit intercurrences, and outcomes. RESULTS: A total of 119 newborns with Down syndrome were recruited, and 112 were selected for analysis. The most common maternal age group was >35 years (72.07%), the most common type of delivery was cesarean section (83.93%), and the majority of cases were male (53.57%). The most common reasons for neonatal intensive care unit hospitalization were congenital heart disease (57.66%) and prematurity (23.21%). The most common form of feeding was a combination of human milk and formula (83.93%). The second most common malformation was duodenal atresia (9.82%). The most common complications during neonatal intensive care unit hospitalization were transient tachypnea of the newborn (63.39%), hypoglycemia (18.75%), pulmonary hypertension (7.14%), and sepsis (7.14%). The mean length of stay in the neonatal intensive care unit was 27 days. The most common outcome was discharge (82.14%). Furthermore, 12.50% of newborns were transferred to an external neonatal intensive care unit, and 6% died. CONCLUSION: Newborns with Down syndrome are more likely to be admitted to the neonatal intensive care unit, and the length of hospital stay is longer due to complications related to congenital malformations common to this syndrome and prematurity.

Epidemiology of congenital malformations of the external ear in Hunan Province, China, from 2016 to 2020.

To describe the epidemiology of congenital malformations of the external ear (CMEE). Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016 to 2020. The prevalence of CMEEs is defined as the number of cases per 1000 fetuses (births and deaths at 28 weeks of gestation and beyond) (unit: ‰). Prevalence and 95% confidence intervals (CI) were calculated by the log-binomial method. Chi-square trend tests (χ2trend) were used to determine trends in prevalence by year. P < .05 was considered statistically significant. Crude odds ratios (ORs) were calculated to examine the association of sex, residence, and maternal age with CMEEs. Our study included 847,755 fetuses, and 14,459 birth defects were identified, including 1227 CMEEs (accounted for 8.49% of birth defects). The prevalences of birth defects and CMEEs were 17.06‰ (95%CI: 16.78-17.33) and 1.45‰ (95%CI: 1.37-1.53), respectively. A total of 185 microtia-anotias were identified, accounting for 15.08% of CMEEs, with a prevalence of 0.22‰ (95%CI: 0.19-0.25). And 1042 other CMEEs were identified, accounting for 84.92% of CMEEs. From 2016 to 2020, the prevalences of birth defects were 18.20‰, 18.00‰, 16.31‰, 16.03‰, and 16.47‰, respectively, showing a downward trend (χ2trend =8.45, P < .01); the prevalences of CMEEs were 1.19‰, 1.62‰, 1.80‰, 1.21‰, and 1.35‰, respectively, with no significant trend (χ2trend =0.09, P = .77). CMEEs were more common in males than females (1.60‰ vs 1.27‰, OR = 1.26, 95%CI: 1.12-1.41), in urban areas than in rural areas (1.77‰ vs 1.23‰, OR = 1.45, 95%CI: 1.29-1.62). The prevalences of CMEEs for maternal age < 20, 20-24, 25-29, 30-34, and ≥ 35 were 1.75‰, 1.27‰, 1.44‰, 1.47‰, and 1.58‰, respectively, with no significant difference (P > .05, reference: 25-29). Most CMEEs were diagnosed by clinical examinations (92.34%), and most CMEEs were diagnosed postpartum (within 7 days) (96.25%). In summary, we have presented the epidemiology of CMEEs in Hunan Province, China. CMEEs were more common in males than females, in urban areas than rural areas, whereas there was no significant difference in prevalence of CMEEs by maternal age. We inferred that CMEEs may be mainly related to genetics, and the mechanism needs to be examined in the future.

Prenatal cannabis use disorder and gastroschisis in California, 2007-19.

BACKGROUND: Gastroschisis is a congenital anomaly of the abdominal wall with an unknown aetiology. Recent trends in the prevalence of gastroschisis suggest that changing environmental or behavioural factors may contribute. We examined whether prenatal cannabis use disorder was associated with gastroschisis. METHODS: The Study of Outcomes of Mothers and Infants is a population-based cohort compiled of California birth records that have been linked to Department of Health Care Access and Information hospitalization, emergency department and ambulatory surgery records. We included 2007-19 singleton live births (n = 5 774 656). Cannabis use disorder was measured by diagnosis codes at any visit during pregnancy or at birth. Gastroschisis was measured by diagnosis or surgical repair procedure codes at birth or during the first year of life. RESULTS: The prevalence of cannabis use disorder was about 1%. The prevalence of gastroschisis was 0.14% and 0.06% among those with and without cannabis use disorder, respectively. There were positive associations between cannabis use disorder and gastroschisis when using a multivariable model [adjusted risk ratio (aRR) = 1.3, 95% confidence interval (CI) 1.0, 1.7) and a matched sample approach (aRR = 1.5, 95% CI 1.1, 2.1). The association varied by maternal age and was largest among people aged >34 years (aRR = 2.5, 95% CI 1.0, 5.8). CONCLUSIONS: We confirm findings of a positive association between cannabis exposure and gastroschisis and add that it is strongest when maternal age is greater than 34 years. More investigation into whether the association is causal, and why the association varies by maternal age, is encouraged.

Advanced maternal age alters cardiac functional and structural adaptations to pregnancy in rats.

A significant number of pregnancies occur at advanced maternal age (>35 yr), which is a risk factor for pregnancy complications. Healthy pregnancies require massive hemodynamic adaptations, including an increased blood volume and cardiac output. There is growing evidence that these cardiovascular adaptations are impaired with age, however, little is known about maternal cardiac function with advanced age. We hypothesized that cardiac adaptations to pregnancy are impaired with advanced maternal age. Younger (4 mo; ∼early reproductive maturity in humans) and aged (9 mo; ∼35 yr in humans) pregnant Sprague-Dawley rats were assessed and compared with age-matched nonpregnant controls. Two-dimensional echocardiographic images were obtained (ultrasound biomicroscopy; under anesthesia) on gestational day 19 (term = 22 days) and compared with age-matched nonpregnant rats (n = 7-9/group). Left ventricular structure and function were assessed using short-axis images and transmitral Doppler signals. During systole, left ventricular anterior wall thickness increased with age in the nonpregnant rats, but there was no age-related difference between the pregnant groups. There were no significant pregnancy-associated differences in left ventricular wall thickness. Calculated left ventricular mass increased with age in nonpregnant rats and increased with pregnancy only in young rats. Compared with young pregnant rats, the aortic ejection time of aged pregnant rats was greater and Tei index was lower. Overall, the greater aortic ejection time and lower Tei index with age in pregnant rats suggest mildly altered cardiac adaptations to pregnancy with advanced maternal age, which may contribute to adverse outcomes in advanced maternal age pregnancies.NEW & NOTEWORTHY We demonstrated that even before the age of reproductive senescence, rats show signs of age-related alterations in cardiac structure that suggests increased cardiac work. Our data also demonstrate, using an in vivo echocardiographic approach, that advanced maternal age in a rat model is associated with altered cardiac function and structure relative to younger pregnant controls.

Epidemiology of congenital polydactyly and syndactyly in Hunan Province, China.

OBJECTIVE: To describe the prevalence and epidemiology of congenital polydactyly and syndactyly in Hunan Province, China, 2016-2020. METHODS: Data were obtained from the Birth Defects Surveillance System in Hunan Province, China, 2016-2020. Prevalence of birth defects (polydactyly or syndactyly) is the number of cases per 1000 births (unit: ‰). Prevalence and 95% confidence intervals (CI) were calculated by the log-binomial method. Chi-square trend tests (χ2trend) were used to determine trends in prevalence by year. Crude odds ratios (ORs) were calculated to examine the association of each demographic characteristic with polydactyly and syndactyly. RESULTS: Our study included 847,755 births, and 14,459 birth defects were identified, including 1,888 polydactyly and 626 syndactyly cases, accounting for 13.06% and 4.33% of birth defects, respectively. The prevalences of total birth defects, polydactyly, and syndactyly were 17.06‰ (95%CI: 16.78-17.33), 2.23‰ (95%CI: 2.13-2.33), and 0.74‰ (95%CI: 0.68-0.80), respectively. Most polydactyly (96.77%) and syndactyly (95.69%) were diagnosed postnatally (within 7 days). From 2016 to 2020, the prevalences of polydactyly were 1.94‰, 2.07‰, 2.20‰, 2.54‰, and 2.48‰, respectively, showing an upward trend (χ2trend = 19.48, P < 0.01); The prevalences of syndactyly were 0.62‰, 0.66‰, 0.77‰, 0.81‰, and 0.89‰, respectively, showing an upward trend (χ2trend = 10.81, P = 0.03). Hand polydactyly (2.26‰ vs. 1.33‰, OR = 1.69, 95%CI: 1.52-1.87) and hand syndactyly (0.43‰ vs. 0.28‰, OR = 1.42, 95%CI: 1.14-1.76) were more common in males than females. Polydactyly (2.67‰ vs. 1.93‰, OR = 1.38, 95%CI: 1.26-1.51) and syndactyly (0.91‰ vs. 0.62‰, OR = 1.47, 95%CI: 1.26-1.72) were more common in urban areas than in rural areas. Compared to maternal age 25-29, hand polydactyly was more common in maternal age < 20 (2.48‰ vs. 1.74‰, OR = 1.43, 95%CI: 1.01-2.02) or ≥ 35 (2.25‰ vs. 1.74‰, OR = 1.30, 95%CI: 1.12-1.50). CONCLUSION: In summary, we have described the prevalence and epidemiology of polydactyly and syndactyly from hospital-based surveillance in Hunan Province, China, 2016-2020. Our findings make some original contributions to the field, which may be valuable for future research.

Developmental programming of reproduction in the female animal.

Successful reproduction is a cornerstone in food animal industry in order to sustain food production for human. Therefore, various methods focusing on genetics and postnatal environment have been identified and applied to improve fertility in livestock. Yet there is evidence indicating that environmental factors during prenatal and/or neonatal life can also impact the function of reproductive system and fertility in the animals during adulthood, which is called the developmental programming of reproduction. The current review summarizes data associated with the developmental origins of reproduction in the female animals. In this regard, this review focuses on the effect of plane of nutrition, maternal body condition, hypoxia, litter size, maternal age, parity, level of milk production and milk components, lactocrine signaling, stress, thermal stress, exposure to androgens, endocrine disrupting chemicals, mycotoxins and pollutants, affliction with infection and inflammation, and maternal gut microbiota during prenatal and neonatal periods on the neuroendocrine system, puberty, health of reproductive organs and fertility in the female offspring. It is noteworthy that these prenatal and neonatal factors do not always exert their effects on the reproductive performance of the female by compromising the development of organs directly related to reproductive function such as hypothalamus, pituitary, ovary, oviduct and uterus. Since they can impair the development of non-reproductive organs and systems modulating reproductive function as well (e.g., metabolic system and level of milk yield in dairy animals). Furthermore, when these factors affect the epigenetics of the offspring, their adverse effects will not be limited to one generation and can transfer transgenerationally. Hence, pinpointing the factors influencing developmental programming of reproduction and considering them in management of livestock operations could be a potential strategy to help improve fertility in food animals.

Comparison of miscarriage rates in low prognosis patients according to the POSEIDON criteria.

OBJECTIVE: The POSEIDON criteria stratified patients with poor ovarian response into four subgroups with exclusive characteristics and assisted reproductive technology success rates. However, limited studies focused on miscarriage in the POSEIDON population. This study aimed to explore whether the miscarriage rate different among low prognosis patients according to POSEIDON criteria. MATERIALS AND METHODS: This is a retrospective observational study. All clinical pregnancies achieved after in vitro fertilization or intracytoplasmic sperm injection treatment between January 1998 and April 2021 were analyzed. The primary outcome was miscarriage, defined as the pregnancy loss before 20 weeks of gestation age. Miscarriage rate was estimated per clinical pregnancy and gestational sac. RESULTS: A total of 1222 clinical pregnancies from 1088 POSEIDON patients met the inclusion criteria. The miscarriage rates per clinical pregnancy in each POSEIDON subgroup were as follows: Group 1: 11.7 %, Group 2: 26.5 %, Group 3: 20.9 %, and Group 4: 37.5 %. The miscarriage rate per gestational sac showed a similar trend as the clinical miscarriage rate. Multivariate regression analysis showed that advanced maternal age is an independent factor for miscarriage (Group 2 vs. 1: OR 2.476; Group 4 vs. 3: OR 2.252). Patients with diminished ovarian reserve (DOR) have higher miscarriage risks but without significance (Group 3 vs. 1: OR 1.322; Group 4 vs. 2: OR 1.202). CONCLUSION: Miscarriage rates differed among low prognosis patients according to the POSEIDON criteria. Age remains a determined risk for miscarriage. DOR might be a potential factor for miscarriage, but it didn't account for a significant impact in POSEIDON patients.

[Advanced maternal age as a risk factor for adverse maternal and perinatal outcomes] / Edad materna avanzada como factor de riesgo de resultados adversos maternos y perinatales.

Introduction: A progressive increase in the age of women at first pregnancy is observed, a situation that has been associated with a greater risk of adverse maternal and perinatal effects. Objective: The aim of this study was to describe the characteristics and the maternal and perinatal outcomes of nulliparas of 40 years and older and compare them with those of nulliparas under 40. Study design: This was a retrospective cohort analysis of a database of pregnancy population who had attended their deliveries in a private university hospital. Results: An association was observed between maternal age ≥ 40 with the maternal compound adverse outcome (OR 1,3; 95% CI: 1,1-1,6), gestational diabetes (OR 3,6; 95% CI: 1,80-3,7), hypertensive disorders/preeclampsia (OR 2,2; 95% CI: 1,6-3,1) and postpartum hemorrhage (4,7; 95% CI: 1,2-16,3), with advanced maternal age persisting as an independent risk factor for the maternal compound adverse outcome (OR 1,3; 95% CI: 1,1 -1,6) and the perinatal compound adverse outcome (OR 1,40; 95% CI: 1,2-1,7) in the multivariate analysis. A higher rate of preterm birth was observed in the group of older nulliparas (OR 1,6; 95% CI: 1,3-2,0) with a higher requirement for admission to NICU for their newborns (OR 1,3; 95% CI: 1,0-1,8). Conclusions: Women with advanced maternal age constitute a high-risk population, whose attention and follow-up would require a differential approach aiming to improve maternal and perinatal outcomes.

Introducción: Se observa un progresivo aumento en la edad de las mujeres al primer embarazo, situación que se ha asociado con mayor riesgo de efectos maternos y perinatales adversos. Objetivo: Describir las características y los resultados maternos y perinatales de nulíparas de 40 años y mayores y compararlos con los de nulíparas menores de 40. Material y métodos: Cohorte retrospectiva de embarazos que atendieron su parto en un hospital privado universitario mediante revisión de registros. Diseño: Se observó asociación entre la edad materna ≥ 40 con el resultado adverso compuesto materno (OR 1.3; IC 95%: 1,1-1,6), DBT g (OR 3,6; IC 95%: 1,8-3,7), enfermedad hipertensiva/PE (OR 2,2; IC 95%: 1,6-3,1) y hemorragia postparto (4,7; IC 95%: 1,2-16.3), persistiendo la edad avanzada como factor de riesgo independiente para el resultado adverso compuesto materno (OR 1,3; IC 95%: 1,1-1,6) y perinatal (OR 1,4; IC 95%: 1,2-1,7) en el análisis multivariado. Se observó mayor tasa de parto pretérmino en el grupo de nulíparas añosas (OR 1,6; IC 95%: 1,3-2,0) con mayor requerimiento de ingreso a UCIN para sus recién nacidos (OR 1,3; IC 95%: 1,0-1,8). Conclusiones: Las mujeres con edad materna avanzada constituyen una población de alto riesgo, cuya atención y seguimiento requeriría un enfoque diferencial que tenga como objetivo mejorar los resultados maternos y perinatales.

Insights into non-informative results from non-invasive prenatal screening through gestational age, maternal BMI, and age analyses.

The discovery of cell-free fetal DNA fragments in the maternal plasma initiated a novel testing method in prenatal care, called non-invasive prenatal screening (NIPS). One of the limitations of NIPS is the necessity for a sufficient proportion of fetal fragments in the analyzed circulating DNA mixture (fetal fraction), otherwise, the sample is uninterpretable. We present the effect of gestational age, maternal body mass index (BMI), and maternal age on the fetal fraction (FF) of the sample. We retrospectively analyzed data from 5543 pregnant women with a single male fetus who underwent NIPS from which 189 samples received a repeat testing due to an insufficient FF. We showed the relationship between the failure rate of the samples after the repeated analysis, the FF, and the gestational age at the first sampling. Next, we found that different maternal BMI categories affect the FF and thus the chance of an informative redraw. A better understanding of the factors affecting the FF will reduce the number of non-informative calls from repeated analyzes. In this study, we provide helpful information to clinicians on how to approach non-informative analyses.

Expanding the Massachusetts Birth Defects Monitoring Program to include additional pregnancy outcomes: Programmatic efforts and impacts on case ascertainment, 2012-2020.

BACKGROUND: Birth defects affect 1 in 33 infants in the United States and are a leading cause of infant mortality. Birth defects surveillance is crucial for informing public health action. The Massachusetts Birth Defects Monitoring Program (MBDMP) began collecting other pregnancy losses (OPLs) in 2011, including miscarriages (<20 weeks gestation) or elective terminations (any gestational age), in addition to live births and stillbirths (≥20 weeks gestation). We describe programmatic changes for adding OPLs and their impact on prevalence estimates. METHODS: Using population-based, statewide, data from the MBDMP (2012-2020), we assessed prevalence per 10,000 live births and 95% confidence intervals (CIs) with and without OPLs overall and for specific birth defects by time period, maternal age, and race/ethnicity. RESULTS: Including OPLs required amending a state statute and promulgating regulations, new data sources, and additional data processing, cleaning, and verification. Overall prevalence with OPLs increased from 257.4 (95% CI: 253.5-261.4) to 333.9 (95% CI: 329.4-338.4) per 10,000; increases were observed in all time periods, age, and race/ethnicity groups. After including OPLs, the prevalence increased for neural tube defects [3.2 (2.7-3.6) to 8.3 (7.6-9.0)], and trisomies 13 [0.5 (0.3-0.7) to 4.1 (3.6-4.6)], 18 [1.5 (1.2-1.9) to 8.2 (7.5-8.9)], and 21 [12.3 (11.4-13.2) to 28.9 (27.6-30.2)]. Cardiovascular defects increased slightly, while prevalence of eye/ear, respiratory, and gastrointestinal defects remained similar. CONCLUSIONS: Adding OPLs required substantial programmatic efforts and resulted in more complete case ascertainment, particularly for certain birth defects. More complete case ascertainment will allow for improved research, screening, and resource allocation.

Maternal Age at Menarche Genes Determines Fetal Growth Restriction Risk.

We aimed to explore the potential link of maternal age at menarche (mAAM) gene polymorphisms with risk of the fetal growth restriction (FGR). This case (FGR)-control (FGR free) study included 904 women (273 FGR and 631 control) in the third trimester of gestation examined/treated in the Departments of Obstetrics. For single nucleotide polymorphism (SNP) multiplex genotyping, 50 candidate loci of mAAM were chosen. The relationship of mAAM SNPs and FGR was appreciated by regression procedures (logistic/model-based multifactor dimensionality reduction [MB-MDR]) with subsequent in silico assessment of the assumed functionality pithy of FGR-related loci. Three mAAM-appertain loci were FGR-linked to genes such as KISS1 (rs7538038) (effect allele G-odds ratio (OR)allelic = 0.63/pperm = 0.0003; ORadditive = 0.61/pperm = 0.001; ORdominant = 0.56/pperm = 0.001), NKX2-1 (rs999460) (effect allele A-ORallelic = 1.37/pperm = 0.003; ORadditive = 1.45/pperm = 0.002; ORrecessive = 2.41/pperm = 0.0002), GPRC5B (rs12444979) (effect allele T-ORallelic = 1.67/pperm = 0.0003; ORdominant = 1.59/pperm = 0.011; ORadditive = 1.56/pperm = 0.009). The haplotype ACA FSHB gene (rs555621*rs11031010*rs1782507) was FRG-correlated (OR = 0.71/pperm = 0.05). Ten FGR-implicated interworking models were founded for 13 SNPs (pperm ≤ 0.001). The rs999460 NKX2-1 and rs12444979 GPRC5B interplays significantly influenced the FGR risk (these SNPs were present in 50% of models). FGR-related mAAM-appertain 15 polymorphic variants and 350 linked SNPs were functionally momentous in relation to 39 genes participating in the regulation of hormone levels, the ovulation cycle process, male gonad development and vitamin D metabolism. Thus, this study showed, for the first time, that the mAAM-appertain genes determine FGR risk.

Optimal timing of GnRH antagonist initiation in IVF-ET: a retrospective cohort study on advanced maternal age women.

Background: Several studies have compared the effects of fixed and flexible gonadotropin releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization and embryo transfer (IVF-ET). However, which GnRH-ant initiation strategy is better remains controversial. Moreover, no studies have assessed the optimal timing of GnRH-ant initiation in women of advanced maternal age (AMA). Methods: In this retrospective cohort study, a total of 472 infertile women aged ≥ 35 years old undergoing their first IVF cycle from August 2015 to September 2021 at a tertiary academic medical center were recruited, of whom 136 followed fixed GnRH-ant protocol and 336 followed flexible GnRH-ant protocol. The primary outcomes measured were the cumulative live birth rate (CLBR) per IVF cycle and the time to live birth (TTLB) from the date of oocyte retrieval. Cox proportional models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of CLBR regarding GnRH-ant timing. Results: No significant difference in CLBR was found between the fixed and flexible GnRH-ant groups (27.9% vs 20.5%, p=0.105). The TTLB was also comparable between groups (10.56 vs 10.30 months, p=0.782). The Kaplan-Meier analysis for CLBR also showed comparable results between groups (P=0.351, HR=0.83; 95%CI: 0.56-1.23). After establishing a multiple Cox proportional hazard model, the fixed GnRH-ant group still had comparable CLBR with the flexible GnRH-ant group (HR=0.85; 95%CI: 0.53-1.38; P=0.518). Subgroup and sensitivity analyses also demonstrated similar results. Conclusion: GnRH-ant protocols can be tailored to the needs of AMA women, and timing of GnRH-ant initiation can be adjusted flexibly.

Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

BACKGROUND: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population. METHODS: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age. RESULTS: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic. CONCLUSIONS: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.

Relationship Between Maternal Age and Macronutrient Content of Colostrum.

BACKGROUND: Little is known about the relationship between maternal age and the macronutrient content of colostrum. RESEARCH AIMS: This study aimed to evaluate the relationship between maternal age and human milk macronutrient content by comparing the concentrations of lactose, proteins, and lipids in the colostrum of women with younger, moderate, and advanced maternal age. METHODS: An observational, cross-sectional study was designed to compare the macronutrient concentrations in the colostrum of women aged < 20 years, 20 to 34 years, and > 34 years (younger, moderate, and advanced maternal age, respectively; n = 33 per group). For each participant, 3 ml of colostrum was collected by manual extraction from the right breast at 10 am, 39-48 hr after delivery, and analyzed using a Miris Human Milk Analyzer. Macronutrient concentrations were compared between the groups using analysis of variance. P < 0.05 was considered significant. RESULTS: Mothers with moderate maternal age had a higher colostrum lipid concentration than those with younger or advanced maternal age (2.3 mg, SD = 1.4 mg vs. 1.5 mg, SD = 1.0 mg vs. 1.6 mg, SD = 0.9 mg, respectively; p = 0.007). Lactose and protein contents in the analyzed samples did not differ among the three study groups. CONCLUSION: This study lends support to the potential variation of lipids in colostrum by maternal age and suggests individual adaptation to the nutritional components of milk to the needs of the infant may be beneficial.

Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age.

BACKGROUND: Pathogenic (P) copy number variants (CNVs) may be associated with second-trimester ultrasound soft markers (USMs), and noninvasive prenatal screening (NIPS) can enable interrogate the entire fetal genome to screening of fetal CNVs. This study evaluated the clinical application of NIPS for detecting CNVs among fetuses with USMs in pregnant women not of advanced maternal age (AMA). RESULTS: Fetal aneuploidies and CNVs were identified in 6647 pregnant women using the Berry Genomics NIPS algorithm.Those with positive NIPS results underwent amniocentesis for prenatal diagnosis. The NIPS and prenatal diagnosis results were analyzed and compared among different USMs. A total of 96 pregnancies were scored positive for fetal chromosome anomalies, comprising 37 aneuploidies and 59 CNVs. Positive predictive values (PPVs) for trisomy 21, trisomy 18, trisomy 13, and sex chromosome aneuploidies were 66.67%, 80.00%, 0%, and 30.43%, respectively. NIPS sensitivity for aneuploidies was 100%. For CNVs, the PPVs were calculated as 35.59% and false positive rate of 0.57%. There were six P CNVs, two successfully identified by NIPS and four missed, of which three were below the NIPS resolution limit and one false negative. The incidence of aneuploidies was significantly higher in fetuses with absent or hypoplastic nasal bone, while that of P CNVs was significantly higher in fetuses with aberrant right subclavian artery (ARSA), compared with other groups. CONCLUSIONS: NIPS yielded a moderate PPV for CNVs in non-AMA pregnant women with fetal USM. However, NIPS showed limited ability in identifying P CNVs. Positive NIPS results for CNVs emphasize the need for further prenatal diagnosis. We do not recommend the use of NIPS for CNVs screening in non-AMA pregnant women with fetal USM, especially in fetuses with ARSA.