Relationship between the natural cessation time of umbilical cord pulsation in full-term newborns delivered vaginally and maternal-neonatal outcomes: a prospective cohort study.

BACKGROUND: To analyze the impact of the time of natural cessation of the umbilical cord on maternal and infant outcomes in order to explore the time of clamping that would be beneficial to maternal and infant outcomes. METHODS: The study was a cohort study and pregnant women who met the inclusion and exclusion criteria at the Obstetrics and Gynecology Department of Qilu Hospital of Shandong University from September 2020 to September 2021. Analysis using Kruskal-Wallis rank sum test, Pearson's Chi-squared test, generalized linear mixed model (GLMM) and repeated measures ANOVA. If the difference between groups was statistically significant, the Bonferroni test was then performed. A two-sided test of P < 0.05 was considered statistically significant. RESULTS: A total of 345 pregnants were included in this study. The subjects were divided into the ≤60 seconds group (n = 134), the 61-89 seconds group (n = 106) and the ≥90 seconds group (n = 105) according to the time of natural arrest of the umbilical cord. There was no statistically significant difference in the amount of postpartum hemorrhage and the need for iron, medication, or supplements in the postpartum period between the different cord spontaneous arrest time groups for mothers (P > 0.05). The weight of the newborns in the three groups was (3316.27 ± 356.70) g, (3387.26 ± 379.20) g, and (3455.52 ± 363.78) g, respectively, and the number of days of cord detachment was 12.00 (8.00, 15.75) days, 10.00 (7.00, 15.00) days and 9.00 (7.00, 13.00) days, respectively, as the time of natural cessation of the cord increased. The neonatal lymphocyte ratio, erythrocyte pressure, and hemoglobin reached a maximum in the 61-89 s group at (7.41 ± 2.16) %, (61.77 ± 8.17) % and (194.52 ± 25.84) g/L, respectively. Lower incidence of neonatal hyperbilirubinemia in the 61-89 s group compared to the ≥90s group 0 vs 4.8 (P < 0.05). CONCLUSIONS: In full-term singleton vaginal births, maternal and infant outcomes are better when waiting for 61-89 s after birth for the cord to stop pulsating naturally, suggesting that we can wait up to 90s for the cord to stop pulsating naturally, and if the cord does not stop pulsating after 90s, artificial weaning may be more beneficial to maternal and infant outcomes.

Antenatal screening for thyroid dysfunction: pre-term birth, low birth-weight, and growth restriction.

OBJECTIVE: To assess pre-term birth, low birth-weight and growth restriction according to maternal thyroid screening results and subsequent treatment. METHODS: This is a nonintervention nested case-control study derived from 10,052 asymptomatic women previously screened during the first trimester marker with anti-thyroid peroxidase antibodies, serum thyroid stimulating hormone, and free thyroxine. Screening results had been classified as positive with one or more markers outside the normal range and referred to an endocrinologist. Cases were 512 women with positive results and information on recommended treatment: 204 thyroxine, propylthiouracil or surgery, and 308 no treatment or only iodine. Controls were a sequential sample of 1292 women with negative results. All cases and controls had information on gestation at delivery or birth-weight. Outcome measures were pre-term birth (<37 weeks), low birth-weight (<2.5 kg) and, for singletons, small for gestational age (SGA; <10th percentile). RESULTS: Among singleton pregnancies, there was a higher prevalence of both pre-term birth (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.21-2.36, p < .002) and low birth-weight (RR 1.72, 95% CI 1.13-2.62, p < .02) in cases compared with controls. An increase in low birth-weight was also present in term pregnancies, but not significant (RR 1.80, 95% CI 0.78-4.14, p = .16), and there was no difference in SGA prevalence (1.24, 95% CI 0.93-1.65, p = .14). Among cases there was no significant difference in these rates according to treatment even after logistic regression, allowing for the individual screening marker levels and maternal weight. CONCLUSIONS: Women with positive thyroid screening results are at increased risk of pre-term birth regardless of thyroid dysfunction or subsequent treatment. An association with low birth-weight is probably secondary to early delivery.

Application of Artificial Intelligence in Infant Movement Classification: A Reliability and Validity Study in Infants Who Were Full-Term and Preterm.

OBJECTIVE: Preterm infants are at high risk of neuromotor disorders. Recent advances in digital technology and machine learning algorithms have enabled the tracking and recognition of anatomical key points of the human body. It remains unclear whether the proposed pose estimation model and the skeleton-based action recognition model for adult movement classification are applicable and accurate for infant motor assessment. Therefore, this study aimed to develop and validate an artificial intelligence (AI) model framework for movement recognition in full-term and preterm infants. METHODS: This observational study prospectively assessed 30 full-term infants and 54 preterm infants using the Alberta Infant Motor Scale (58 movements) from 4 to 18 months of age with their movements recorded by 5 video cameras simultaneously in a standardized clinical setup. The movement videos were annotated for the start/end times and presence of movements by 3 pediatric physical therapists. The annotated videos were used for the development and testing of an AI algorithm that consisted of a 17-point human pose estimation model and a skeleton-based action recognition model. RESULTS: The infants contributed 153 sessions of Alberta Infant Motor Scale assessment that yielded 13,139 videos of movements for data processing. The intra and interrater reliabilities for movement annotation of videos by the therapists showed high agreements (88%-100%). Thirty-one of the 58 movements were selected for machine learning because of sufficient data samples and developmental significance. Using the annotated results as the standards, the AI algorithm showed satisfactory agreement in classifying the 31 movements (accuracy = 0.91, recall = 0.91, precision = 0.91, and F1 score = 0.91). CONCLUSION: The AI algorithm was accurate in classifying 31 movements in full-term and preterm infants from 4 to 18 months of age in a standardized clinical setup. IMPACT: The findings provide the basis for future refinement and validation of the algorithm on home videos to be a remote infant movement assessment.

First-trimester and early-second-trimester transvaginal cervical length before 16 weeks among women with preterm and term birth: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the differences in first-trimester and early-second-trimester transvaginal cervical length between patients with spontaneous preterm birth and those with term birth. DATA SOURCES: PubMed, MEDLINE, Embase, and the Cochrane Library were systematically searched through August 2023. STUDY ELIGIBILITY CRITERIA: Studies had to include (1) transvaginal cervical length measurement before 16+0 weeks of gestation and (2) transvaginal cervical length measurement in a population of patients who delivered preterm and at term. Abstracts, studies with duplicated data, and those with cervical length measured by transabdominal ultrasound scan were excluded. METHODS: K.W.C. and J.L. searched for, screened, and reviewed the articles independently. The quality of the studies was assessed using the Newcastle-Ottawa scale. Mean differences were calculated using a random-effects model and pooled through a meta-analysis. RESULTS: A total of 5727 published articles were identified. Only 10 studies (which analyzed 22,151 pregnancies) met the inclusion criteria. All studies excluded iatrogenic preterm birth. Transvaginal cervical length was significantly shorter in women with spontaneous preterm birth than in those who delivered at term (mean difference, -0.97; 95% confidence interval, -1.65 to -0.29; P=.005; I2=69%). When a linear technique was used to measure transvaginal cervical length, a significantly shorter transvaginal cervical length was associated with spontaneous preterm birth as opposed to term birth (mean difference, -1.09; 95% confidence interval, -1.96 to -0.21; P=.02; I2=77%). A shorter transvaginal cervical length measured by other techniques was also associated with spontaneous preterm birth before 34 to 35 weeks (mean difference, -1.87; 95% confidence interval, -3.04 to -0.70; P=.002; I2=0%). When studies where interventions were given for a "short" cervix or studies with a mean transvaginal cervical length ≥40 mm were excluded, a significantly shorter transvaginal cervical length was observed among those with spontaneous preterm birth (mean difference, -1.13; 95% confidence interval, -1.89 to -0.37; P=.004; mean difference, -0.86; 95% confidence interval, -1.67 to -0.04; P=.04; respectively). The optimal transvaginal cervical length cutoff was 38 to 39 mm, yielding pooled sensitivity of 0.80, specificity of 0.45, positive likelihood ratio of 1.16, negative likelihood ratio of 0.33, diagnostic odds ratio of 5.12, and an area under the curve of 0.75. CONCLUSION: Women with spontaneous preterm birth had significantly shorter transvaginal cervical length before 16 weeks of gestation compared with those who delivered at term. The linear method and the 2-line method are acceptable techniques for measuring transvaginal cervical length.

Neurodevelopmental outcomes at age 3 years after moderate preterm, late preterm and early term birth: the Japan Environment and Children's Study.

OBJECTIVE: To assess the association between gestational age classification at birth and the risk of neurodevelopmental impairments at age 3 years. DESIGN: Cohort study using the Japan Environment and Children's Study database. PATIENTS: A total of 86 138 singleton children born without physical abnormalities at 32-41 weeks of gestation enrolled between January 2011 and March 2014. MAIN OUTCOME MEASURES: Neurodevelopmental impairment, evaluated using the Ages and Stages Questionnaire (third edition). METHODS: Logistic regression analysis was used to evaluate the risk of neurodevelopmental impairment in moderate preterm, late preterm and early term children compared with term children after adjusting for socioeconomic and perinatal factors. RESULTS: The respective adjusted ORs (95% CIs) of incidence of scores below the cut-off value (<-2.0 SD) at age 3 years for moderate preterm, late preterm and early term births, compared with full-term births, were as follows: communication, 2.40 (1.54 to 3.73), 1.43 (1.19 to 1.72) and 1.11 (1.01 to 1.21); gross motor, 2.55 (1.69 to 3.85), 1.62 (1.36 to 1.93) and 1.20 (1.10 to 1.30); fine motor, 1.93 (1.34 to 2.78), 1.55 (1.35 to 1.77) and 1.08 (1.01 to 1.15); problem solving, 1.80 (1.22 to 2.68), 1.36 (1.19 to 1.56) and 1.07 (1.00 to 1.14) and personal-social, 2.09 (1.29 to 3.40), 1.32 (1.07 to 1.63) and 1.00 (0.91 to 1.11). CONCLUSION: Moderate preterm, late preterm and early term births were associated with developmental impairment at age 3 years compared with full-term births, with increasing prematurity. Careful follow-up of non-full-term children by paediatricians and other healthcare providers is necessary for early detection of neurodevelopmental impairment and implementation of available intervention.

Association between early-term birth and hypoglycaemia in large-for-gestational-age neonates:A retrospective cohort study.

BACKGROUND: The effect of early-term birth on the development of hypoglycaemia in large-for-gestational-age (LGA) neonates is yet to be clarified. This study aimed to clarify the association between hypoglycaemia and early-term birth in LGA neonates. METHODS: This single-centre retrospective cohort study evaluated LGA neonates born at term at Tsurugi Municipal Handa Hospital, Japan. Blood glucose levels were measured immediately and at 1, 2, and 4 hours after birth. The association between early-term birth and hypoglycaemia was evaluated using logistic regression analysis. The prevalence of severe hypoglycaemia and hypoglycaemia according to its timing of development was analysed using Fisher's exact test. RESULTS: In total, 295 neonates were included. Among them, 113 neonates (38.3%) were born at early term and 91 infants (30.8%) had hypoglycaemia. Logistic regression analysis showed a significant association between early-term birth and hypoglycaemia (adjusted odds ratio [95% confidence interval]:2.691 [1.597 to 4.535]). However, there was no significant between-group difference among those with severe hypoglycaemia. CONCLUSIONS: Among LGA neonates, early-term birth is positively associated with neonatal hypoglycaemia. This indicates that among LGA neonates, those born at early term require more careful observation for hypoglycaemia than do those born at later term. J. Med. Invest. 70 : 476-482, August, 2023.

Impact of moderate-to-late preterm birth on neurodevelopmental outcomes in young children: Results from retrospective longitudinal follow-up with nationally representative data.

This study investigated the relationship between moderate-to-late preterm (MLPT) birth and the risk of neurodevelopmental impairments (NIs) in young children compared with the risks associated with very preterm (VPT) and full-term (FT) birth based on nationally representative large-scale population data. Retrospective follow-up was conducted over 71 months for 738,733 children who were born and participated in the Korean National Health Screening Program for Infants and Children (NHSPIC) between 2011 and 2013. Using a data linkage between the NHSPIC and Korean healthcare claim information, data on birth year, sex, delivery type, birth weight, growth abnormality, gestational age, breastfeeding history, maternal age, NIs, multiple gestation, preterm labor, premature rupture of membranes (PROM), gestational diabetes, gestational hypertension, smoking during pregnancy, and socioeconomic status were collected and included in the final analysis. Cox proportional hazards models were applied to identify the impact of gestational age on NI risk, with all variables adjusted as appropriate. Overall, 0.9% and 3.8% rates of VPT and MLPT births were identified, respectively. NI incidence was highest among VPT children (34.7%), followed by MLPT (23.9%) and FT (18.2%) children. Both VPT (hazard ratio [HR], 1.45; 95% confidence interval [CI], 1.03 to 2.05) and MLPT (HR, 1.21; 95% CI, 1.04 to 1.41) births were associated with increased NI risk. Low birth weight, PROM, and smoking during pregnancy were also associated with increased NI risk, while longer breastfeeding and higher socioeconomic status were associated with decreased risk. Special attention must be given to NIs for both VPT and MLPT children.

The association between post-term births and autism spectrum disorders: an updated systematic review and meta-analysis.

BACKGROUND: This study aimed to conduct a meta-analysis to determine whether post-term birth has an increased risk of ASD. MATERIALS AND METHODS: To retrieve eligible studies regarding the effect of post-term and ASD in children, major databases including PubMed, Scopus, and Web of Science were searched. A random effect model was used for meta-analysis. For assessing the quality of included studies, the GRADE checklist was used. RESULTS: In total, 18 records were included with 1,412,667 sample populations from 12 countries. The pooled estimates of RR and OR showed a significant association between post-term birth and ASD among children, respectively (RR = 1.34, 95% CI 1.10 to 1.58) and (OR = 1.47, 95% CI 1.03 to 1.91). There was no heterogeneity among the studies that reported the risk of ASD among children based on RR (I2 = 6.6%, P = 0.301). There was high heterogeneity in the studies reported risk of ASD based on OR (I2 = 94.1%, P = 0.000). CONCLUSION: Post-term births still occur relatively frequently (up to 5-10%) even in developed countries. Our results showed that post-term birth is an increased risk of ASD, although high heterogeneity was found among the studies reported based on adjusted and crude forms, however, after subgroup analysis by gender, this heterogeneity disappeared among males.

Educational achievement to age 11 years in children born at late preterm and early term gestations.

OBJECTIVE: To investigate the effects of being born late preterm (LPT, 34-36 weeks' gestation) or early term (37-38 weeks) on children's educational achievement between ages 5 and 11 years. DESIGN: A series of observational studies of longitudinal linked health and education data. SETTING: The Born-in-Bradford (BiB) birth cohort study, which recruited mothers during pregnancy between 2007 and 2011. PARTICIPANTS: The participants are children born between 2007 and 2011. Children with missing data, looked-after-children, multiple births and births post-term were excluded. The sample size varies by age according to amount of missing data, from 7860 children at age 5 years to 2386 at age 11 years (8031 at age 6 years and 5560 at age 7 years). MAIN OUTCOME MEASURES: Binary variables of whether a child reached the 'expected' level of overall educational achievement across subjects at the ages of 5, 6, 7 and 11 years. The achievement levels are measured using standardised teacher assessments and national tests. RESULTS: Compared with full-term births (39-41 weeks), there were significantly increased adjusted odds of children born LPT, but not early term, of failing to achieve expected levels of overall educational achievement at ages 5 years (adjusted OR (aOR) 1.72,95% CI 1.34 to 2.21) and 7 years (aOR 1.46, 95% CI 1.08 to 1.97) but not at age 11 years (aOR 1.51, 95% CI 0.99 to 2.30). Being born LPT still had statistically significant effects on writing and mathematics at age 11 years. CONCLUSIONS: There is a strong association between LPT and education at age 5 years, which remains strong and statistically significant through age 11 years for mathematics but not for other key subjects.

Association of maternal birth weight and maternal preterm birth with subsequent risk for adverse reproductive outcomes: The Women's Health Initiative.

BACKGROUND: Advancements in medical technology and pharmacologic interventions have drastically improved survival of infants born preterm and low birth weight, but knowledge regarding the long-term health impacts of these individuals is limited and inconsistent. AIM: To investigate whether an individual's birthweight or history of being born preterm increases the risk of an adverse reproductive outcome. STUDY DESIGN: Nested case-control study within the Women's Health Initiative. SUBJECTS: 79,934 individuals who self-reported their personal birthweight category and/or preterm birth status. OUTCOMES MEASURES: Self-reported pregnancy outcomes: subfertility, miscarriage, stillbirth, preeclampsia, gestational diabetes, gestational hypertension, preterm birth, low birthweight infant, high birthweight infant. Logistic regression models were used to estimate unadjusted and adjusted odds ratios (OR). RESULTS: After adjustments, individuals reporting their birthweight <6lbs. were 20 % more likely to have a stillbirth or 70 % more likely to have a low birthweight infant and were less likely to have a full-term birth or high birthweight infant during their pregnancy. Individuals reporting a birthweight ≥10 lbs. were more likely to have a high birthweight infant (OR 3.49, 95 % CI 2.73-4.39) and less likely to have a low birthweight infant (OR 0.64, 95 % CI 0.47-0.82). Individuals born preterm were at increased risk for infertility, miscarriage, preeclampsia, gestational diabetes, and delivering a preterm or low birthweight infant. CONCLUSIONS: As more individuals born preterm and/or low birthweight survive to adulthood, the incidence and prevalence of poor reproductive outcomes may increase. Women born at extremes of birthweight and prematurity may need to be monitored more closely during their own pregnancies.

Preterm or early term birth and risk of attention-deficit/hyperactivity disorder: a national cohort and co-sibling study.

PURPOSE: To examine risks of attention-deficit/hyperactivity disorder (ADHD) in preterm and early term birth survivors, and potential sex-specific differences. METHODS: A national cohort study was conducted of all 4061,795 singletons born in Sweden in 1973-2013 who survived infancy, followed up for ADHD identified from nationwide diagnoses and medications through 2018. Poisson regression was used to compute prevalence ratios (PRs), adjusting for sociodemographic and perinatal factors. Co-sibling analyses assessed for confounding by unmeasured shared familial (genetic or environmental) factors. RESULTS: ADHD prevalences by gestational age at birth were 12.1% for extremely preterm (22-27 weeks), 7.0% for moderately preterm (28-33 weeks), 5.7% for late preterm (34-36 weeks), 6.1% for all preterm (<37 weeks), 5.2% for early term (37-38 weeks), and 4.5% for full-term (39-41 weeks). Adjusted PRs comparing extremely preterm, all preterm, or early term versus full-term, respectively, were 2.35 (95% CI, 2.15-2.57), 1.28 (1.25-1.31), and 1.12 (1.10-1.13) among males, and 2.46 (2.17-2.78), 1.24 (1.20-1.28), and 1.08 (1.06-1.10) among females (P < .001 for each). These associations were virtually unchanged after controlling for shared familial factors. Both spontaneous and medically indicated preterm birth were associated with ADHD (adjusted PRs, 1.21; 95% CI, 1.18-1.24; and 1.39; 1.34-1.43, respectively). CONCLUSIONS: In this large cohort, preterm and early term birth were associated with increased risks of ADHD in males and females, independently of covariates and shared familial factors.

Cesarean sections and early-term births according to Robson classification: a population-based study with more than 17 million births in Brazil.

BACKGROUND: Cesarean section (CS) rates are increasing worldwide and are associated with negative maternal and child health outcomes when performed without medical indication. However, there is still limited knowledge about the association between high CS rates and early-term births. This study explored the association between CSs and early-term births according to the Robson classification. METHODS: A population-based, cross-sectional study was performed with routine registration data of live births in Brazil between 2012 and 2019. We used the Robson classification system to compare groups with expected high and low CS rates. We used propensity scores to compare CSs to vaginal deliveries (1:1) and estimated associations with early-term births using logistic regression. RESULTS: A total of 17,081,685 live births were included. Births via CS had higher odds of early-term birth (OR 1.32; 95% CI 1.32-1.32) compared to vaginal deliveries. Births by CS to women in Group 2 (OR 1.50; 95% CI 1.49-1.51) and 4 (OR 1.57; 95% CI 1.56-1.58) showed the highest odds of early-term birth, compared to vaginal deliveries. Increased odds of an early-term birth were also observed among births by CS to women in Group 3 (OR 1.30, 95% CI 1.29-1.31), compared to vaginal deliveries. In addition, live births by CS to women with a previous CS (Group 5 - OR 1.36, 95% CI 1.35-1.37), a single breech pregnancy (Group 6 - OR 1.16; 95% CI 1.11-1.21, and Group 7 - OR 1.19; 95% CI 1.16-1.23), and multiple pregnancies (Group 8 - OR 1.46; 95% CI 1.40-1.52) had high odds of an early-term birth, compared to live births by vaginal delivery. CONCLUSIONS: CSs were associated with increased odds of early-term births. The highest odds of early-term birth were observed among those births by CS in Robson Groups 2 and 4.

Pre-pregnancy and pregnancy disorders, pre-term birth and the risk of cerebral palsy: a population-based study.

BACKGROUND: Cerebral palsy (CP) is the most common cause of childhood physical disability whose aetiology remains unclear in most cases. Maternal pre-existing and pregnancy complications are recognized risk factors of CP but the extent to which their effects are mediated by pre-term birth is unknown. METHODS: Population-based cohort study in Sweden including 2 055 378 singleton infants without congenital abnormalities, born between 1999 and 2019. Data on maternal and pregnancy characteristics and diagnoses of CP were obtained by individual record linkages of nationwide Swedish registries. Exposure was defined as maternal pre-pregnancy and pregnancy disorders. Inpatient and outpatient diagnoses were obtained for CP after 27 days of age. Adjusted rate ratios (aRRs) were calculated, along with 95% CIs. RESULTS: A total of 515 771 (25%) offspring were exposed to maternal pre-existing chronic disorders and 3472 children with CP were identified for a cumulative incidence of 1.7 per 1000 live births. After adjusting for potential confounders, maternal chronic cardiovascular or metabolic disorders, other chronic diseases, mental health disorders and early-pregnancy obesity were associated with 1.89-, 1.24-, 1.26- and 1.35-times higher risk (aRRs) of CP, respectively. Most notably, offspring exposed to maternal antepartum haemorrhage had a 6-fold elevated risk of CP (aRR 5.78, 95% CI, 5.00-6.68). Mediation analysis revealed that ∼50% of the effect of these associations was mediated by pre-term delivery; however, increased risks were also observed among term infants. CONCLUSIONS: Exposure to pre-existing maternal chronic disorders and pregnancy-related complications increases the risk of CP in offspring. Although most infants with CP were born at term, pre-term delivery explained 50% of the overall effect of pre-pregnancy and pregnancy disorders on CP.

Paternal and maternal psychiatric history and risk of preterm and early term birth: A nationwide study using Swedish registers.

BACKGROUND: Women with psychiatric diagnoses are at increased risk of preterm birth (PTB), with potential life-long impact on offspring health. Less is known about the risk of PTB in offspring of fathers with psychiatric diagnoses, and for couples where both parents were diagnosed. In a nationwide birth cohort, we examined the association between psychiatric history in fathers, mothers, and both parents and gestational age. METHODS AND FINDINGS: We included all infants live-born to Nordic parents in 1997 to 2016 in Sweden. Psychiatric diagnoses were obtained from the National Patient Register. Data on gestational age were retrieved from the Medical Birth Register. Associations between parental psychiatric history and PTB were quantified by relative risk (RR) and two-sided 95% confidence intervals (CIs) from log-binomial regressions, by psychiatric disorders overall and by diagnostic categories. We extended the analysis beyond PTB by calculating risks over the whole distribution of gestational age, including "early term" (37 to 38 weeks). Among the 1,488,920 infants born throughout the study period, 1,268,507 were born to parents without a psychiatric diagnosis, of whom 73,094 (5.8%) were born preterm. 4,597 of 73,500 (6.3%) infants were born preterm to fathers with a psychiatric diagnosis, 8,917 of 122,611 (7.3%) infants were born preterm to mothers with a pscyhiatric diagnosis, and 2,026 of 24,302 (8.3%) infants were born preterm to both parents with a pscyhiatric diagnosis. We observed a shift towards earlier gestational age in offspring of parents with psychiatric history. The risks of PTB associated with paternal and maternal psychiatric diagnoses were similar for different psychiatric disorders. The risks for PTB were estimated at RR 1.12 (95% CI [1.08, 1.15] p < 0.001) for paternal diagnoses, at RR 1.31 (95% CI [1.28, 1.34] p < 0.001) for maternal diagnoses, and at RR 1.52 (95% CI [1.46, 1.59] p < 0.001) when both parents were diagnosed with any psychiatric disorder, compared to when neither parent had a psychiatric diagnosis. Stress-related disorders were associated with the highest risks of PTB with corresponding RRs estimated at 1.23 (95% CI [1.16, 1.31] p < 0.001) for a psychiatry history in fathers, at 1.47 (95% CI [1.42, 1.53] p < 0.001) for mothers, and at 1.90 (95% CI [1.64, 2.20] p < 0.001) for both parents. The risks for early term were similar to PTB. Co-occurring diagnoses from different diagnostic categories increased risk; for fathers: RR 1.10 (95% CI [1.07, 1.13] p < 0.001), 1.15 (95% CI [1.09, 1.21] p < 0.001), and 1.33 (95% CI [1.23, 1.43] p < 0.001), for diagnoses in 1, 2, and ≥3 categories; for mothers: RR 1.25 (95% CI [1.22, 1.28] p < 0.001), 1.39 (95% CI [1.34, 1.44] p < 0.001) and 1.65 (95% CI [1.56, 1.74] p < 0.001). Despite the large sample size, statistical precision was limited in subgroups, mainly where both parents had specific psychiatric subtypes. Pathophysiology and genetics underlying different psychiatric diagnoses can be heterogeneous. CONCLUSIONS: Paternal and maternal psychiatric history were associated with a shift to earlier gestational age and increased risk of births before full term. The risk consistently increased when fathers had a positive history of different psychiatric disorders, increased further when mothers were diagnosed and was highest when both parents were diagnosed.

Serum cytokines in second trimester pregnancy and their relationship with spontaneous preterm births in the Ribeirão Preto and São Luiz cohorts.

OBJECTIVE: To evaluate the association between second trimester plasma cytokine levels in asymptomatic pregnant women and preterm births (PTB) in an attempt to identify a possible predictor of preterm birth. METHODS: The study design was a nested case-control study including women with singleton a gestational age between 20-25(+ 6) weeks from two Brazilian cities. The patients were interviewed, Venous blood samples were collected. The participants were again evaluated at birth. A total of 197 women with PTB comprised the case group. The control group was selected among term births (426 patients). Forty-one cytokines were compared between groups. RESULTS: When only spontaneous PTB were analyzed, GRO, sCD40L and MCP-1 levels were lower in the case group (p < 0.05). Logarithmic transformation was performed for cytokines with discrepant results, which showed increased levels of IL-2 in the group of spontaneous PTB (p < 0.05). In both analyses, the incidence of maternal smoking and of a history of preterm delivery differed significantly between the case and control groups. In multivariate analysis, only serum GRO levels differed between the case and control groups. CONCLUSION: Lower second trimester serum levels of GRO in asymptomatic women are associated with a larger number of PTB. This finding may reflect a deficient maternal inflammatory response.

The relationship between extreme ambient temperature and small for gestational age: A cohort study of 1,436,480 singleton term births in China.

Studies have shown that exposure to extreme ambient temperature can contribute to adverse pregnancy outcomes, however, results across studies have been inconsistent. We aimed to evaluate the relationships between trimester-specific extreme temperature exposures and fetal growth restriction indicated by small for gestational age (SGA) in term pregnancies, and to assess whether and to what extent this relationship varies between different geographic regions. We linked 1,436,480 singleton term newborns (2014-2016) in Hubei Province, China, with a sub-district-level temperature exposures estimated by a generalized additive spatio-temporal model. Mixed-effects logistic regression models were employed to estimate the effects of extreme cold (temperature ≤5th percentile) and heat exposures (temperature >95th percentile) on term SGA in three different geographic regions, while adjusting for the effects of maternal age, infant sex, the frequency of health checks, parity, educational level, season of birth, area-level income, and PM2.5 exposure. We also stratified our analyses by infant sex, maternal age, urban‒rural type, income categories and PM2.5 exposure for robustness analyses. We found that both cold (OR:1.32, 95% CI: 1.25-1.39) and heat (OR:1.17, 95% CI: 1.13-1.22) exposures during the third trimester significantly increased the risk of SGA in the East region. Only extreme heat exposure (OR:1.29, 95% CI: 1.21-1.37) during the third trimester was significantly related to SGA in the Middle region. Our findings suggest that extreme ambient temperature exposure during pregnancy can lead to fetal growth restriction. Governments and public health institutions should pay more attention to environmental stresses during gestation, especially in the late stage of the pregnancy.

The Relationship of Preterm, Term, and Post-Term Births to Maternal Stress and Human Milk Cortisol Levels.

Introduction: Maternal stress can lead to changes in the composition of human breast milk. The present study evaluates cortisol levels in the breast milk of mothers after giving birth preterm, term, or post-term, and ascertains whether the levels are associated with maternal stress. Materials and Methods: Included in the study were mothers who gave birth vaginally after 32 weeks of gestation between January and April 2022. The breast milk was expressed with an electronic pump under the supervision of a nurse on day 7 following birth, and 2 mL samples of the milk were transferred into microtubes and stored at -80°C. Stress in the mothers was measured using the perceived stress scale developed by Cohen et al. The human breast milk cortisol levels were determined using an enzyme-linked immunoassay in a single session. Results: A total of 90 mothers, including 30 with preterm births, 38 with term births, and 22 with post-term births, were included in the study. The median stress scale score was 28 (17-50) and the median breast milk cortisol level was 0.49 ng/mL (0.1-1.96 ng/mL). A significant positive correlation was noted between the stress scale scores and breast milk cortisol levels (r = 0.56, p < 0.01). The breast milk cortisol levels and maternal stress scale scores were significantly higher in the preterm birth group than in the term birth group (p = 0.011 and p = 0.013, respectively). Conclusion: Although there is an association between maternal stress and preterm labor and milk cortisol levels, we believe that more studies are needed to establish a causal link.

Birth Weight in Consecutive Pregnancies and Maternal Cardiovascular Disease Mortality Among Spontaneous and Iatrogenic Term Births: A Population-Based Cohort Study.

Knowledge on the association between offspring birth weight and long-term risk of maternal cardiovascular disease (CVD) mortality is often based on firstborn infants without consideration of women's consecutive births. We studied long-term CVD mortality according to offspring birth weight patterns among women with spontaneous and iatrogenic term deliveries in Norway (1967-2020). We constructed birth weight quartiles (Qs) by combining standardized birth weight with gestational age in quartiles (Q1, Q2/Q3, and Q4) for the women's first 2 births. Mortality was estimated using Cox regression and expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). Changes in offspring birth weight quartiles were associated with long-term maternal CVD mortality. Compared with women who had 2 term infants in Q2/Q3, women with a first offspring in Q2/Q3 and a second in Q1 had higher mortality risk (HR = 1.33, 95% CI: 1.18, 1.50), while risk was lower if the second offspring was in Q4 (HR = 0.78, 95% CI: 0.67, 0.91). The risk increase associated with having a first infant in Q1 was eliminated if the second offspring was in Q4 (HR = 0.99, 95% CI: 0.75, 1.31). These patterns were similar for women with iatrogenic and spontaneous deliveries. Inclusion of information from subsequent births revealed heterogeneity in maternal CVD mortality which was not captured when using only information based on the first offspring.

County-Level Maternal Vulnerability and Preterm Birth in the US.

Importance: Appreciation for the effects of neighborhood conditions and community factors on perinatal health is increasing. However, community-level indices specific to maternal health and associations with preterm birth (PTB) have not been assessed. Objective: To examine the association of the Maternal Vulnerability Index (MVI), a novel county-level index designed to quantify maternal vulnerability to adverse health outcomes, with PTB. Design, Setting, and Participants: This retrospective cohort study used US Vital Statistics data from January 1 to December 31, 2018. Participants included 3 659 099 singleton births at 22 plus 0/7 to 44 plus 6/7 weeks of gestation born in the US. Analyses were conducted from December 1, 2021, through March 31, 2023. Exposure: The MVI, a composite measure of 43 area-level indicators, categorized into 6 themes reflecting physical, social, and health care landscapes. Overall MVI and theme were stratified by quintile (very low to very high) by maternal county of residence. Main Outcomes and Measures: The primary outcome was PTB (gestational age <37 weeks). Secondary outcomes were PTB categories: extreme (gestational age ≤28 weeks), very (gestational age 29-31 weeks), moderate (gestational age 32-33 weeks), and late (gestational age 34-36 weeks). Multivariable logistic regression quantified associations of MVI, overall and by theme, with PTB, overall and by PTB category. Results: Among 3 659 099 births, 298 847 (8.2%) were preterm (male, 51.1%; female, 48.9%). Maternal race and ethnicity included 0.8% American Indian or Alaska Native, 6.8% Asian or Pacific Islander, 23.6% Hispanic, 14.5% non-Hispanic Black, 52.1% non-Hispanic White, and 2.2% with more than 1 race. Compared with full-term births, MVI was higher for PTBs across all themes. Very high MVI was associated with increased PTB in unadjusted (odds ratio [OR], 1.50 [95% CI, 1.45-1.56]) and adjusted (OR, 1.07 [95% CI, 1.01-1.13]) analyses. In adjusted analyses of PTB categories, MVI had the largest association with extreme PTB (adjusted OR, 1.18 [95% CI, 1.07-1.29]). Higher MVI in the themes of physical health, mental health and substance abuse, and general health care remained associated with PTB overall in adjusted models. While the physical health and socioeconomic determinant themes were associated with extreme PTB, physical health, mental health and substance abuse, and general health care themes were associated with late PTB. Conclusions and Relevance: The findings of this cohort study suggest that MVI was associated with PTB even after adjustment for individual-level confounders. The MVI is a useful measure for county-level PTB risk that may have policy implications for counties working to lower preterm rates and improve perinatal outcomes.

Bumetanide potentiates the anti-seizure and disease-modifying effects of midazolam in a noninvasive rat model of term birth asphyxia.

Birth asphyxia and the resulting hypoxic-ischemic encephalopathy (HIE) are highly associated with perinatal and neonatal death, neonatal seizures, and an adverse later-life outcome. Currently used drugs, including phenobarbital and midazolam, have limited efficacy to suppress neonatal seizures. There is a medical need to develop new therapies that not only suppress neonatal seizures but also prevent later-life consequences. We have previously shown that the loop diuretic bumetanide does not potentiate the effects of phenobarbital in a rat model of birth asphyxia. Here we compared the effects of bumetanide (0.3 or 10 mg/kg i.p.), midazolam (1 mg/kg i.p.), and a combination of bumetanide and midazolam on neonatal seizures and later-life outcomes in this model. While bumetanide at either dose was ineffective when administered alone, the higher dose of bumetanide markedly potentiated midazolam's effect on neonatal seizures. Median bumetanide brain levels (0.47-0.53 µM) obtained with the higher dose were in the range known to inhibit the Na-K-Cl-cotransporter NKCC1 but it remains to be determined whether brain NKCC1 inhibition was underlying the potentiation of midazolam. When behavioral and cognitive alterations were examined over three months after asphyxia, treatment with the bumetanide/midazolam combination, but not with bumetanide or midazolam alone, prevented impairment of learning and memory. Furthermore, the combination prevented the loss of neurons in the dentate hilus and aberrant mossy fiber sprouting in the CA3a area of the hippocampus. The molecular mechanisms that explain that bumetanide potentiates midazolam but not phenobarbital in the rat model of birth asphyxia remain to be determined.