Whole-genome sequencing in autism identifies hot spots for de novo germline mutation.

De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We investigated global patterns of germline mutation by whole-genome sequencing of monozygotic twins concordant for ASD and their parents. Mutation rates varied widely throughout the genome (by 100-fold) and could be explained by intrinsic characteristics of DNA sequence and chromatin structure. Dense clusters of mutations within individual genomes were attributable to compound mutation or gene conversion. Hypermutability was a characteristic of genes involved in ASD and other diseases. In addition, genes impacted by mutations in this study were associated with ASD in independent exome-sequencing data sets. Our findings suggest that regional hypermutation is a significant factor shaping patterns of genetic variation and disease risk in humans.

Shifts in the Distribution of Births by Gestational Age: United States, 2014-2022.

Objectives-This report presents changes in the distribution of singleton births by gestational age in the United States for 2014-2022, by maternal age and race and Hispanic origin. Methods-Data are based on all birth certificates for singleton births registered in the United States from 2014 to 2022. Gestational age is measured in completed weeks using the obstetric estimate and categorized as early preterm (less than 34 weeks), late preterm (34-36 weeks), total preterm (less than 37 weeks), early term (37-38 weeks), full term (39-40 weeks), and late- and post-term (41 and later weeks). Data are shown by maternal age and race and Hispanic origin. Single weeks of gestation at term (37-41 weeks) are also examined. Results-Despite some fluctuation in most gestational age categories during the pandemic years of 2020-2022, trends from 2014 to 2022 demonstrate a shift towards shorter gestational ages. Preterm and early-term birth rates rose from 2014 to 2022 (by 12% and 20%, respectively), while full-term and lateand post-term births declined (by 6% and 28%, respectively). Similar shifts for each gestational age category were seen across maternal age and race and Hispanic-origin groups. By single week of gestation at term, the largest change was for births at 37 weeks (an increase of 42%).

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.

Infant Mortality in the United States, 2021: Data From the Period Linked Birth/Infant Death File.

Objective-This report presents 2021 infant mortality statistics by age at death, maternal race and Hispanic origin, maternal age, gestational age, leading causes of death, and maternal state of residence. Trends in infant mortality are also examined. Methods-Descriptive tabulations of data are presented and interpreted for infant deaths and infant mortality rates using the 2021 period linked birth/infant death file. The linked birth/infant death file is based on birth and death certificates registered in all 50 states and the District of Columbia. Results-A total of 19,928 infant deaths were reported in the United States in 2021, up 2% from 2020. The U.S. infant mortality rate was 5.44 infant deaths per 1,000 live births, essentially unchanged from the rate of 5.42 in 2020. The neonatal mortality rate was essentially unchanged from 3.56 in 2020 to 3.49 in 2021, but the postneonatal mortality rate increased from 1.86 to 1.95. The overall infant mortality rate increased for infants of Asian non-Hispanic women and declined for infants of Dominican women in 2021 compared with 2020; changes in rates for the other race and Hispanic-origin groups were not significant. Infants of Black non-Hispanic women had the highest mortality rate (10.55) in 2021, followed by infants of Native Hawaiian or Pacific Islander non-Hispanic and American Indian or Alaska Native non-Hispanic (7.76 and 7.46, respectively), Hispanic (4.79), White non-Hispanic (4.36), and Asian non-Hispanic (3.69) women. By gestational age, infants born very preterm (less than 28 weeks of gestation) had the highest mortality rate (353.76), 170 times as high as that for infants born at term (37-41 weeks of gestation) (2.08). The five leading causes of infant death in 2021 were the same as in 2020. Infant mortality rates by state for 2021 ranged from a low of 2.77 in North Dakota to a high of 9.39 in Mississippi.

Births: Final Data for 2021.

Objectives-This report presents 2021 data on U.S. births according to a variety of characteristics. Trends in fertility patterns and maternal and infant characteristics are described and interpreted.

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.

Single-cell proteomics reveals decreased abundance of proteostasis and meiosis proteins in advanced maternal age oocytes.

Advanced maternal age is associated with a decline in oocyte quality, which often leads to reproductive failure in humans. However, the mechanisms behind this age-related decline remain unclear. To gain insights into this phenomenon, we applied plexDIA, a multiplexed data-independent acquisition, single-cell mass spectrometry method, to analyze the proteome of oocytes from both young women and women of advanced maternal age. Our findings primarily revealed distinct proteomic profiles between immature fully grown germinal vesicle and mature metaphase II oocytes. Importantly, we further show that a woman's age is associated with changes in her oocyte proteome. Specifically, when compared to oocytes obtained from young women, advanced maternal age oocytes exhibited lower levels of the proteasome and TRiC complex, as well as other key regulators of proteostasis and meiosis. This suggests that aging adversely affects the proteostasis and meiosis networks in human oocytes. The proteins identified in this study hold potential as targets for improving oocyte quality and may guide future studies into the molecular processes underlying oocyte aging.

Cause-of-death Data From the Fetal Death File,2018-2020.

Objectives-This report presents data on fetal cause of death by maternal age, maternal race and Hispanic origin, fetal sex, period of gestation, birthweight, and plurality.

Infant Mortality in the United States, 2020: Data From the Period Linked Birth/Infant Death File.

Objectives-This report presents 2020 infant mortality statistics by age at death, maternal race and Hispanic origin, maternal age, gestational age, leading causes of death, and maternal state of residence. Trends in infant mortality are also examined.

REPRODUCTIVE AGEING: Altered histone modification landscapes underpin defects in uterine stromal cell decidualization in aging females.

In Brief: Advanced maternal age is associated with a higher rate of pregnancy complications that are unrelated to karyotypic abnormalities of the oocyte. This study shows that the murine uterine stroma undergoes profound epigenetic changes affecting active and repressive histone modification profiles that are associated with impaired endometrial functionality and underpin the decline in reproductive performance of aged females. Abstract: Decidualization describes the transformation of the uterine stroma in response to an implanting embryo, a process critical for supporting the development of the early embryo, for ensuring normal placentation and ultimately for a healthy reproductive outcome. Maternal age has been found to impede the progression of decidualization, heightening the risk of reproductive problems. Here, we set out to comprehensively characterize this deficit by pursuing transcriptomic and epigenomic profiling approaches specifically in the uterine stromal cell (UtSC) compartment of young and aged female mice. We find that UtSCs from aged females are globally far less responsive to the decidualization stimulus triggered by exposure to the steroid hormones estrogen and progesterone. Despite an overall transcriptional hyperactivation of genes that are differentially expressed as a function of maternal age, the hormonally regulated genes specifically fail to be activated in aged UtSCs. Moreover, even in their unstimulated 'ground' state, UtSCs from aged females are epigenetically distinct, as determined by genomic enrichment profiling for the active and repressive histone marks H3K4me3 and H3K9me3, respectively. We find that many hormone-inducible genes exhibit a profound lack of promoter-associated H3K4me3 in aged UtSCs, implying that a significant enrichment of active histone marks prior to gene stimulation is required to enable the elicitation of a rapid transcriptional response. With this combination of criteria, our data highlight specific deficits in epigenetic marking and gene expression of ion channels and vascular markers. These results point to fundamental defects in muscle-related and perivascular niche functions of the uterine stroma with advanced maternal age.

Childhood adversity and the risk of gestational diabetes: A population-based cohort study of nulliparous pregnant women.

AIMS: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications, and though it may be linked to childhood adversity, the effect of different types of adversity remains unclear. Childhood adversity is linked to a younger maternal age, which may hide the overall impact of adversity on GDM risk. We therefore aimed to explore the association between different types of childhood adversity and GDM while accounting for the potential impact of maternal age. METHODS: We used Danish nation-wide register data, including 208,207 women giving birth for the first time from 2004 to 2018. Five adversity groups were used to examine the effect of childhood adversity on GDM risk: (1) low (referent group), (2) early life material deprivation, (3) persistent deprivation, (4) loss or threat of loss within the family and (5) high adversity. RESULTS: 5375 women were diagnosed with GDM in the study population (2.6% absolute risk). Compared to women who experienced low adversity, the other adversity groups had a higher GDM risk (absolute difference [%]) directly; early material deprivation (0.64% [95% CI 0.44; 0.84]), persistent deprivation (0.63% [0.41; 0.86]), loss or threat of loss (0.73% [0.42; 1.05]) and high adversity (0.80% [0.32; 1.27]). The indirect effect of maternal age attenuated the total effect of childhood adversity on GDM by an absolute difference of 0.25%-0.46%. CONCLUSIONS: Experiencing childhood adversity to any extent is associated with a higher risk of GDM. Interventions aimed at preventing childhood adversity may have a positive effect in reducing GDM burden and the associated health risks.

Impact of aneuploidy on reproductive success in young infertile women: prospective analysis.

RESEARCH QUESTION: What is the clinical outcome of the first attempt at conception between two embryo selection methods, blastocyst morphology and preimplantation genetic testing for aneuploidies (PGT-A), chosen at the initial physician IVF consultation? DESIGN: In this prospective analysis, a clinical decision regarding embryo selection, blastocyst morphology (group A) or PGT-A (group B) was made during initial physician IVF consultation. Female infertility patients were matched based on maternal age (mean 32.6 ± 3.6 years; range 25-43 years) and a similar time frame of oocyte retrieval. The primary outcome was live birth rate from the initial consultation to the first conception attempt for all female patients and for a subset analysis of patients aged <35 years. RESULTS: The inclusion of PGT-A (group B) for embryo selection during the initial physician IVF consultation resulted in 23 additional women out of the total 100 achieving a healthy live birth following the first conception attempt in this maternally age-matched infertile population (group B = 72.0% versus group A = 49.0%; P = 0.0014). This same benefit was observed for age-matched, younger infertility patients (<35 years), with live birth rates from the initial consultation being significantly higher when the upfront clinical decision included PGT-A for embryo selection (group B = 76.7% versus group A = 53.4%; P = 0.0052). Interestingly, 17 women from group B would have received an aneuploid embryo transfer if selection had been determined by blastocyst morphology alone, as their best-grade embryo was aneuploid. CONCLUSIONS: This prospective analysis from the initial physician IVF consultation revealed that euploid embryo selection significantly improved live birth potential with the first conception attempt, even for younger women with infertility.

The ovarian stimulation regimen does not affect aneuploidy or blastocyst rate.

RESEARCH QUESTION: Could the total dose (<3000 IU or ≥3000 IU) and type of exogenous gonadotrophin (i.e. recombinant FSH and/or human menopausal gonadotrophin [HMG]) influence aneuploidy and blastulation rates and produce different reproductive outcomes? DESIGN: This retrospective, observational, multicentre cohort study included a total of 8466 patients undergoing IVF using autologous oocytes and preimplantation genetic testing for aneuploidies. Participants were divided according to the dosage of total gonadotrophins and stratified by maternal age. RESULTS: The aneuploidy rates, pregnancy outcomes and cumulative live birth rates (CLBR) were similar among women who received total gonadotrophin dosages of <3000 or ≥3000 IU. No statistical differences were reported in the blastulation rate with lower or higher gonadotrophin dosages. Women receiving a higher amount of HMG during ovarian stimulation had a lower aneuploidy rate (P = 0.02); when stratified according to age, younger women with a higher HMG dosage had lower aneuploidy rates (P< 0.001), while no statistical differences were observed in older women with higher or lower HMG dosages. No significant differences were observed in IVF outcomes or CLBR. CONCLUSIONS: High doses of gonadotrophins were not associated with rate of aneuploidy. However, an increased fraction of HMG in younger women was associated with a lower aneuploidy rate. The study demonstrated that the total gonadotrophin dosage did not influence aneuploidy, reproductive outcomes or CLBR. The increased gonadotrophin and HMG dosages used for ovarian stimulation did not precede aneuploidy, and the use of HMG should be evaluated on a case-by-case basis, according to the individual's characteristics and infertility type.

Ongoing pregnancy rates in single euploid frozen embryo transfers remain unaffected by female age: a retrospective study.

RESEARCH QUESTION: Is female age a significant factor in the likelihood of an ongoing pregnancy in single euploid frozen embryo transfers (FET)? DESIGN: Retrospective study of 1923 single euploid FET cycles in 1464 women, either in a natural cycle or a hormone replacement therapy cycle. The primary outcome was the ongoing pregnancy rate (OPR). RESULTS: There were 990 (51.48%) ongoing pregnancies among 1923 included transfers. The OPR were 51.4%, 49.1%, 53.3% and 52.3% for women aged ≤35, >35-≤37, >37-≤40 and >40 years at oocyte retrieval (OCR), without a significant trend for decreasing OPR (P = 0.679). No significant differences in female age at embryo transfer (P = 0.609) and female age at OCR (P = 0.816) were found between the groups (ongoing pregnancy versus no pregnancy or miscarriage). Women who received good-quality embryos (P < 0.001), had a lower body mass index (BMI) (P < 0.001), had achieved at least one pregnancy previously (P < 0.001), and underwent natural cycle endometrial preparation (P < 0.001) were more likely to achieve an ongoing pregnancy. Multivariable regression analysis (adjusted for BMI, embryo quality and endometrial preparation) did not show a significant effect of female age at OCR on achieving an ongoing pregnancy. Compared with women aged ≤35 years, none of the age groups had significantly higher or lower OPR. A multinomial regression analysis showed that BMI, embryo quality and endometrial preparation were associated with miscarriage/no pregnancy versus ongoing pregnancy (P = 0.001, 0.001 and 0.001, respectively). Female age had no significant association with either outcome. CONCLUSIONS: Female age in itself does not have a substantial impact on the OPR in single euploid FET cycles, but the OPR is impacted significantly by embryo quality, BMI, previous parity, and a natural cycle endometrial preparation protocol.

Twenty-four-hour urinary protein excretion in uncomplicated singleton pregnancy.

BACKGROUND: Twenty-four-hour urinary total protein excretion is an essential parameter used for evaluation of renal function and early detection of gestational complications. However, data on reference ranges of 24-hour urinary total protein excretion in normal pregnancy are scarce. OBJECTIVE: This study aimed to determine reference ranges for 24-hour urinary total protein excretion in a population with uncomplicated singleton pregnancies using a standard method for urinary total protein. In addition, the values of 24-hour urinary total protein were stratified by maternal age and prepregnancy body mass index. STUDY DESIGN: This study was based on a prospective cohort study in Shenzhen, China. The pregnant women were enrolled at their first prenatal clinical visit. All the participants were instructed to collect 24-hour urine samples during the following successive gestational periods: 6+0 to 13+6, 14+0 to 27+6, and 28+0 to 41+6 weeks. Total urinary protein excretion was analyzed by a colorimetric method. Ultimately, the study encompassed a total of 4844 pregnant women with uncomplicated pregnancies. The nonparametric percentile method was used to determine reference ranges for 24-hour urinary total protein excretion during different trimesters in women with uncomplicated pregnancies (excluding those with previous kidney disorders, gestational or chronic hypertension, preeclampsia, and pregestational diabetes mellitus, among others). RESULTS: The 24-hour urinary total protein levels expressed as medians and percentiles (5th, 95th) for each trimester were as follows: 72.0 (28.4, 165.0), 88.0 (34.0, 185.0), and 108.0 (37.5, 258.0) mg in the first, second, and third trimesters, respectively. A significant increase in 24-hour urinary total protein excretion was observed throughout pregnancy (all P values <.001). Moreover, 24-hour urinary total protein levels were higher in the older (≥35 years) than in the younger (<35 years) group from mid-gestation. Specifically, the median (interquartile range) 24-hour urinary total protein levels by age were 72.2 (50.6-100.0) vs 70.5 (50.5-100.0) mg, 85.8 (62.0-117.0) vs 96.0 (68.0-127.8) mg, and 106.6 (76.0-146.2) vs 114.7 (81.5-153.6) mg in the first, second, and third trimesters, respectively. In addition, 24-hour proteinuria was significantly increased in higher-weight (overweight or obese) subgroups compared with lower-weight (underweight or normal-weight) subgroups (all P values <.05). CONCLUSION: Our study provides reference values for 24-hour urinary total protein excretion with apparently uncomplicated pregnancies. Understanding these changes in low-risk pregnancies is essential for optimizing maternal management.

Maternal and Perinatal Factors Associated With Childhood Brain Tumors: A Case-Control Study in Vietnam.

INTRODUCTION: Brain cancer is the leading cause of cancer-related deaths in children and the majority of childhood brain tumors are diagnosed without determination of their underlying etiology. Little is known about risk factors for childhood brain tumors in Vietnam. The objective of this case-control study was to identify maternal and perinatal factors associated with brain tumors occurring in young Vietnamese children and adolescents. METHODS: We conducted a hospital-based case-control study at Viet Duc University Hospital in Hanoi, Vietnam. Cases consisted of children with brain tumors aged 0-14 years old admitted to the hospital from January 2020 to July 2022 while the controls were age and sex-matched hospitalized children diagnosed with head trauma. Perinatal characteristics were abstracted from hospital medical records and maternal medical, behavioral, and sociodemographic factors were collected through in-person interviews. Conditional logistic regression models were used to examine maternal and perinatal factors associated with childhood brain tumors. RESULTS: The study sample included 220 children (110 cases and 110 controls) whose average age was 8.9 years and 41.8% were girls. Children born to mothers aged greater than 30 years at the time of the child's birth had a higher risk of childhood brain tumors compared to those born to mothers aged from 18 to 30 years old (OR = 2.55; 95% CI: 1.13-5.75). Additionally low maternal body mass index prior to the current pregnancy of <18.5 kg/m2 significantly increased the odds of having a child with a brain tumor in relation to normal maternal body mass index from 18.5-22.9 kg/m2 (OR = 3.19; 95% CI: 1.36 - 7.50). CONCLUSION: Advanced maternal age and being markedly underweight were associated with an increased odds of having a child with a brain tumor. A population-based study with larger sample size is needed to confirm and extend the present findings.

History of multifetal gestation and long-term maternal mortality.

BACKGROUND: Multifetal gestation could be associated with higher long-term maternal mortality because it increases the risk of pregnancy complications such as preeclampsia and preterm birth, which are in turn linked to postpartum cardiovascular risk. OBJECTIVES: We examined whether spontaneously conceived multifetal versus singleton gestation was associated with long-term maternal mortality in a racially diverse U.S. METHODS: We ascertained vital status as of 2016 via linkage to the National Death Index and Social Security Death Master File of 44,174 mothers from the Collaborative Perinatal Project (CPP; 1959-1966). Cox proportional hazards models with maternal age as the time scale assessed associations between history of spontaneous multifetal gestation (in the last CPP observed pregnancy or prior pregnancy) and all-cause and cardiovascular mortality, adjusted for demographics, smoking status, and preexisting medical conditions. We calculated hazard ratios (HR) for all-cause and cause-specific mortality over the study period and until age 50, 60, and 70 years (premature mortality). RESULTS: Of eligible participants, 1672 (3.8%) had a history of multifetal gestation. Participants with versus without a history of multifetal gestation were older, more likely to have a preexisting condition, and more likely to smoke. By 2016, 51% of participants with and 38% of participants without a history of multifetal gestation had died (unadjusted all-cause HR 1.14, 95% confidence interval [CI] 1.07, 1.23). After adjustment for smoking and preexisting conditions, a history of multifetal gestation was not associated with all-cause (adjusted HR 1.00, 95% CI 0.93, 1.08) or cardiovascular mortality (adjusted HR 0.99, 95% CI 0.87, 1.11) over the study period. However, history of multifetal gestation was associated with an 11% lower risk of premature all-cause mortality (adjusted HR 0.89, 95% CI 0.82, 0.96). CONCLUSIONS: In a cohort with over 50 years of follow-up, history of multifetal gestation was not associated with all-cause mortality, but may be associated with a lower risk of premature mortality.

Mother's age at menarche is associated with odds of preterm delivery: A case-control study.

OBJECTIVE: There is a secular trend towards earlier age of menarche in the US and globally. Earlier age at menarche (AAM) has been associated with metabolic disorders that increase risk for preterm delivery (PTD), yet no studies in the US have investigated whether AAM influences risk of PTD. This study tested the hypothesis that AAM is associated with PTD. DESIGN: A case-control study. SETTING: The Boston Medical Center (BMC) in Boston, Massachusetts. POPULATION OR SAMPLE: 8264 mother-newborn dyads enrolled at birth at BMC between 1998 and 2019, of which 2242 mothers had PTD (cases) and 6022 did not have PTD (controls). METHODS: Multivariable-adjusted logistic regression models and restricted cubic splines were used to examine the association between AAM and risk of PTD. The combined impact of AAM and age at delivery on the risk of PTD was also examined. MAIN OUTCOME MEASURES: Preterm delivery and gestational age (GA) was defined by maternal last menstrual period and early ultrasound documented in medical records. RESULTS: Maternal age at delivery was 28.1 ± 6.5 years and AAM was 12.85 ± 1.86 years. Multivariable-adjusted cubic spline suggested an inverse dose-response association of AAM with odds of PTD and, consistently, a positive association with GA. A 1-year earlier AAM was associated with 5% (95% CI 2%-8%) higher odds of PTD, after adjustment for maternal year of birth, parity, maternal place of birth, education, smoking status and Mediterranean-style diet score. The association between AAM and PTD was stronger among older mothers whose age at delivery was ≥35 years. CONCLUSIONS: Earlier AAM is associated with higher odds for PTD, and this association is stronger among women at advanced reproductive age.

Association between maternal age and sex-based neonatal free triiodothyronine levels.

BACKGROUND: Advanced maternal age may affect the intrauterine environment and increase the risk of neurodevelopmental disorders in offspring. Thyroid hormones are critical for fetal neurological development but whether maternal age influences fetal thyroid hormone levels in euthyroid mothers is unknown. OBJECTIVE: This study evaluated the association between cord blood thyroid hormones and maternal age, fetal sex, maternal thyroid function, and other perinatal factors. METHODS: The study population consisted of 203 healthy women with term singleton pregnancies who underwent elective cesarean section. Maternal levels of free T3 (fT3), free T4 (fT4) and TSH before delivery, and cord levels of fT3, fT4 and TSH were measured. Spearman's correlation coefficient and multiple linear regression analyses were performed to determine the correlation between cord thyroid hormone parameters and maternal characteristics. RESULTS: There were no significant differences in maternal serum or cord blood thyroid hormone levels between male and female births. In multivariate linear regression analysis, maternal age and maternal TSH values were negatively associated with the cord blood levels of fT3 in all births, after adjusting for confounding factors. Maternal age was more closely associated with the cord blood levels of fT3 in female than in male births. CONCLUSION: The inverse association between maternal age and cord blood levels of fT3 in euthyroid pregnant women suggested an impact of maternal aging on offspring thyroid function.

Mothers' school starting age and infant health.

We study the effects of women's school starting age on the infant health of their offspring. In Spain, children born in December start school a year earlier than those born the following January, despite being essentially the same age. We follow a regression discontinuity design to compare the health at birth of the children of women born in January versus the previous December, using administrative, population-level data. We find small and insignificant effects on average weight at birth, but, compared to the children of December-born mothers, the children of January-born mothers are more likely to have very low birthweight. We then show that January-born women have the same educational attainment and the same partnership dynamics as December-born women. However, they finish school later and are (several months) older when they have their first child. Our results suggest that maternal age is a plausible mechanism behind our estimated impacts of school starting age on infant health.