Pregnancy Complications and Long-Term Mortality in a Diverse Cohort.

BACKGROUND: Pregnancy complications are associated with increased risk of development of cardiometabolic diseases and earlier mortality. However, much of the previous research has been limited to White pregnant participants. We aimed to investigate pregnancy complications in association with total and cause-specific mortality in a racially diverse cohort and evaluate whether associations differ between Black and White pregnant participants. METHODS: The Collaborative Perinatal Project was a prospective cohort study of 48 197 pregnant participants at 12 US clinical centers (1959-1966). The Collaborative Perinatal Project Mortality Linkage Study ascertained participants' vital status through 2016 with linkage to the National Death Index and Social Security Death Master File. Adjusted hazard ratios (aHRs) for underlying all-cause and cause-specific mortality were estimated for preterm delivery (PTD), hypertensive disorders of pregnancy, and gestational diabetes/impaired glucose tolerance (GDM/IGT) using Cox models adjusted for age, prepregnancy body mass index, smoking, race and ethnicity, previous pregnancies, marital status, income, education, previous medical conditions, site, and year. RESULTS: Among 46 551 participants, 45% (21 107 of 46 551) were Black, and 46% (21 502 of 46 551) were White. The median time between the index pregnancy and death/censoring was 52 years (interquartile range, 45-54). Mortality was higher among Black (8714 of 21 107 [41%]) compared with White (8019 of 21 502 [37%]) participants. Overall, 15% (6753 of 43 969) of participants had PTD, 5% (2155 of 45 897) had hypertensive disorders of pregnancy, and 1% (540 of 45 890) had GDM/IGT. PTD incidence was higher in Black (4145 of 20 288 [20%]) compared with White (1941 of 19 963 [10%]) participants. The following were associated with all-cause mortality: preterm spontaneous labor (aHR, 1.07 [95% CI, 1.03-1.1]); preterm premature rupture of membranes (aHR, 1.23 [1.05-1.44]); preterm induced labor (aHR, 1.31 [1.03-1.66]); preterm prelabor cesarean delivery (aHR, 2.09 [1.75-2.48]) compared with full-term delivery; gestational hypertension (aHR, 1.09 [0.97-1.22]); preeclampsia or eclampsia (aHR, 1.14 [0.99-1.32]) and superimposed preeclampsia or eclampsia (aHR, 1.32 [1.20-1.46]) compared with normotensive; and GDM/IGT (aHR, 1.14 [1.00-1.30]) compared with normoglycemic. P values for effect modification between Black and White participants for PTD, hypertensive disorders of pregnancy, and GDM/IGT were 0.009, 0.05, and 0.92, respectively. Preterm induced labor was associated with greater mortality risk among Black (aHR, 1.64 [1.10-2.46]) compared with White (aHR, 1.29 [0.97-1.73]) participants, while preterm prelabor cesarean delivery was higher in White (aHR, 2.34 [1.90-2.90]) compared with Black (aHR, 1.40 [1.00-1.96]) participants. CONCLUSIONS: In this large, diverse US cohort, pregnancy complications were associated with higher mortality nearly 50 years later. Higher incidence of some complications in Black individuals and differential associations with mortality risk suggest that disparities in pregnancy health may have life-long implications for earlier mortality.

Developmental coordination disorder in preterm children: A systematic review and meta-analysis.

This study aimed to review the prevalence of developmental coordination disorder (DCD) in individuals born preterm and systematically explore this prevalence according to gestational age and different assessment cut-offs and compare it to full-term peers. The eligibility criteria were observational and experimental studies reporting the prevalence of DCD in preterm individuals. A systematic search was performed in databases from inception until March 2022. Two independent reviewers performed the selection. Study quality assessment was performed using the checklists from Joanna Briggs Institute (JBI). Data analysis was performed on Excel and Review Manager Software 5.4. Among the 1774 studies identified, 32 matched the eligibility criteria. The pooled estimate rate of the DCD rate in preterm was 21% (95% confidence interval [CI] 17.8-24.3). The estimate rates were higher as gestational age decreased, and preterm children are two times more likely to have DCD than their full-term peers risk ratio (RR) 2.2 (95% CI 1.77-2.79). The limitation was high heterogeneity between studies; the assessment tools, cut-off points and age at assessment were diverse. This study provided evidence that preterm children are at higher risk for DCD than full-term children, and the risks increased as gestational age decreased.

Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia.

AIM: Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations. METHODS: We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses. RESULTS: Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results. CONCLUSION: Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.

Systemic inflammation, enteropathogenic E. Coli, and micronutrient insufficiencies in the first trimester as possible predictors of preterm birth in rural Bangladesh: a prospective study.

BACKGROUND: An incomplete understanding of preterm birth is especially concerning for low-middle income countries, where preterm birth has poorer prognoses. While systemic proinflammatory processes are a reportedly normal component of gestation, excessive inflammation has been demonstrated as a risk factor for preterm birth. There is minimal research on the impact of excessive maternal inflammation in the first trimester on the risk of preterm birth in low-middle income countries specifically. METHODS: Pregnant women were enrolled at the rural Bangladesh site of the National Institute of Child Health Global Network Maternal Newborn Health Registry. Serum samples were collected to measure concentrations of the inflammatory markers C-reactive protein (CRP) and Alpha-1-acid glycoprotein (AGP), and stool samples were collected and analyzed for enteropathogens. We examined associations of maternal markers in the first-trimester with preterm birth using logistic regression models. CRP and AGP were primarily modeled with a composite inflammation predictor. RESULTS: Out of 376 singleton births analyzed, 12.5% were preterm. First trimester inflammation was observed in 58.8% of all births, and was significantly associated with increased odds of preterm birth (adjusted odds ratio [aOR] = 2.23; 95% confidence interval [CI]: 1.03, 5.16), independent of anemia. Maternal vitamin B12 insufficiency (aOR = 3.33; 95% CI: 1.29, 8.21) and maternal anemia (aOR = 2.56; 95% CI: 1.26, 5.17) were also associated with higher odds of preterm birth. Atypical enteropathogenic E. coli detection showed a significant association with elevated AGP levels and was significantly associated with preterm birth (odds ratio [OR] = 2.36; 95% CI: 1.21, 4.57), but not associated with CRP. CONCLUSIONS: Inflammation, anemia, and vitamin B12 insufficiency in the first trimester were significantly associated with preterm birth in our cohort from rural Bangladesh. Inflammation and anemia were independent predictors of premature birth in this low-middle income setting where inflammation during gestation was widespread. Further research is needed to identify if infections such as enteropathogenic E. coli are a cause of inflammation in the first trimester, and if intervention for infection would decrease preterm birth.

Development and validation of a self-management self-efficacy scale for premature birth prevention (SMSE-PBP) for women of childbearing age.

BACKGROUND: This study aimed to develop and evaluate the validity and reliability of a self-management self-efficacy for premature birth prevention (SMSE-PBP) in women of childbearing age (WCA). METHODS: Instrument development and validation were undertaken in three phases: conceptualization, item generation and evaluation of content validity, and evaluation of construct and concurrent validity and reliability. Data were analyzed using exploratory and second-order confirmatory factor analyses, and concurrent validity was examined using Pearson's correlation coefficients. The reliability was analyzed using omega hierarchical and Cronbach's ⍺. RESULTS: Content validity was assessed by experts and cognitive interviews of WCA. The SMSE-PBP consists of a second-order 3-dimension and 10-factor scale with 60 items; therefore, the construct and concurrent validity of the SMSE-PBP were supported. The omega values were 0.93 for pre-pregnancy SMSE-PBP, 0.92 for pregnancy SMSE-PBP, and 0.94 for hospital SMSE-PBP. Cronbach's ⍺ was 0.88 for pre-pregnancy SMSE-PBP, 0.96 for pregnancy SMSE-PBP, and 0.96 for hospital SMSE-PBP. CONCLUSIONS: The SMSE-PBP scale is valid and reliable for WCA; it is helpful for WCA and health professionals to assess women's SMSE-PBP and pre-pregnancy, pregnancy, or hospital SMSE-PBP. The next steps should include assessing the relationship with pregnancy health behaviors.

Associations between neonatal nutrition and visual outcomes in 7-year-old children born very preterm.

PURPOSE: There is uncertainty about the effect of increased neonatal protein intake on neurodevelopmental outcomes following preterm birth. The aim of this study was to assess the effect of a change in neonatal nutrition protocol at a major tertiary neonatal intensive care unit intended to increase protein intake on ophthalmic and visual development in school-age children born very preterm. METHODS: The study cohort comprised children (n = 128) with birthweight <1500 g or gestational age < 30 weeks born at Auckland City Hospital before (OldPro group, n = 55) and after (NewPro group, n = 73) a reformulation of parenteral nutrition that resulted in increased total protein intake during the first postnatal week and decreased carbohydrate, total parenteral fluid and sodium intake. Clinical and psychophysical vision assessments were completed at 7 years' corrected age, including visual acuity, global motion perception (a measure of dorsal stream function), stereoacuity, ocular motility and ocular health. Composite measures of favourable overall visual, binocular and functional visual outcomes along with individual vision measures were compared between the groups using logistic and linear regression models. RESULTS: Favourable overall visual outcome did not differ between the two groups. However, global motion perception was better in the NewPro group (p = 0.04), whereas the OldPro group were more likely to have favourable binocular visual outcomes (60% vs. 36%, p = 0.02) and passing stereoacuity (p = 0.02). CONCLUSIONS: These results indicate subtle but complex associations between early neonatal nutrition after very preterm birth and visual development at school age.

Achieving sufficient milk supply supports mothers to cope with premature birth.

AIM: To explore whether and how expressing breast milk is perceived as helpful in coping with negative emotions due to premature birth by mothers of very low birth weight (VLBW) infants. METHODS: Qualitative interviews and a retrospective cross-sectional questionnaire with mothers of VLBW infants were conducted and analysed using an exploratory sequential mixed-method design. Hypotheses were built using qualitative content analysis and quantitatively tested using multivariate regression analysis. RESULTS: Interviews with 12 mothers and questionnaires of 518 mothers were analysed. Coping with prematurity by expressing milk was seen as a way to maintain the caregiving role for the mothers, where three relevant factors arouse: making up for what happened, providing the best for their infant and fear of low milk supply. Quantitative analysis showed that mothers with a high milk supply (Coef. = 1.1, p < 0.000) and more feelings of guilt due to premature birth (Coef. = -0.1; p = 0.015) perceived expressing breast milk significantly more as a resource for coping. CONCLUSION: This study adds knowledge on how expressing breast milk for their VLBW infant may support mothers in coping with premature birth, by revealing the association with milk supply and feelings of guilt due to premature birth.

Efficacy of parent-child interaction therapy for children born premature.

BACKGROUND: Premature children are known to be at a high risk of developing behavioral problems. This study examined the effectiveness of parent-child interaction therapy (PCIT) in reducing behavioral problems in young children born premature. METHODS: The study included 18 child-parent pairs with children born at less than 35 weeks of gestation (range: 23-34 weeks, median: 31.0 weeks) and aged 27-52 months (median: 38.0 months). They were assigned to either the PCIT group (n = 7) or the non-PCIT group (n = 11) based on maternal desire for treatment. The study was designed to examine the effects of PCIT. Specifically, the Eyberg Child Behavior Inventory (ECBI) intensity score, ECBI problem score, and Parenting Stress Index Short Form (PSI-SF) scores were compared before treatment and after 6 months. RESULTS: In the PCIT group, the mean ECBI intensity score was 135.7 (SD = 13.5; T-score = 64) at baseline and 90.1 (SD = 15.5; T-score = 46) at post-assessment, the mean ECBI problem score was 9.8 (SD = 1.9; T-score = 54) at baseline and 4.4 (SD = 3.1; T-score = 44) at post-assessment, the mean PSI-SF total score was 60.1 (SD = 4.8; 95%tile) at baseline and 49.6 (SD = 5.6; 85%tile) at post-assessment, showing a significant improvement (ECBI intensity scores: p < 0.001, d = 2.03; ECBI problem scores: p < 0.001, d = 1.94; PSI-SF total scores: p = 0.004, d = 0.86). On the other hand, none of the scores showed significant change in the non-PCIT group. CONCLUSIONS: The PCIT can be considered as a potential treatment option for behavioral problems in young children born premature.

The impact of the COVID-19 pandemic on antenatal care provision and associated mental health, obstetric and neonatal outcomes.

OBJECTIVES: The COVID-19 pandemic imposed many challenges on pregnant women, including rapid changes to antenatal care aimed at reducing the societal spread of the virus. This study aimed to assess how the pandemic affected perinatal mental health and other pregnancy and neonatal outcomes in a tertiary unit in Queensland, Australia. METHODS: This was a retrospective cohort study of pregnant women booked for care between March 2019 - June 2019 and March 2020 - June 2020. A total of 1984 women were included with no confirmed cases of COVID-19. The primary outcome of this study was adverse maternal mental health defined as an Edinburgh Postnatal Depression Scale score of ≥13 or an affirmative response to 'EPDS Question 10'. Secondary outcomes were preterm birth <37 weeks and <32 weeks, mode of birth, low birth weight, malpresentation in labour, hypertensive disease, anaemia, iron/vitamin B12 deficiency, stillbirth and a composite of neonatal morbidity and mortality. RESULTS: There were no differences in the primary perinatal mental health outcomes. The rates of composite adverse neonatal outcomes (27 vs. 34 %, p<0.001) during the pandemic were higher; however, there was no difference in perinatal mortality (p=1.0), preterm birth (p=0.44) or mode of delivery (p=0.38). CONCLUSIONS: Although there were no adverse consequences on maternal mental health during the pandemic, there was a concerning increase in neonatal morbidity potentially due to the altered model of maternity care implemented in the early COVID-19 pandemic.

Determinants of prematurity in urban Indonesia: a meta-analysis.

OBJECTIVES: Indonesia is the fifth country with the highest number of preterm births worldwide. More than a third of neonatal deaths in Indonesia were attributed to preterm birth. Residential areas affected the occurrence of preterm birth due to differing socioeconomic and environmental conditions. Many studies have investigated the determinants of prematurity in Indonesia, however, most of them were performed in rural areas. This study is the first meta-analysis describing the determinants of preterm birth in urban Indonesia, which aimed to become the foundation upon implementing the most suitable preventative measure and policy to reduce the rate of preterm birth. METHODS: We collected all published papers investigating the determinants of preterm birth in urban Indonesia from PubMed MEDLINE and EMBASE, using keywords developed from the following key concepts: "preterm birth", "determinants", "risk factors", "Indonesia" and the risk factors, such as "high-risk pregnancy", "anemia", "pre-eclampsia", and "infections". Exclusion criteria were multicenter studies that did not perform a specific analysis on the Indonesian population or did not separate urban and rural populations in their analysis, and articles not available in English or Indonesian. The Newcastle Ottawa Scale was used to assess the risk of bias. This systematic review was registered in PROSPERO. RESULTS: Sixteen articles were included in the analysis and classified into five categories: genetic factors, nutrition, smoking, pregnancy characteristics or complications, and disease-related characteristics. CONCLUSIONS: Our meta-analysis revealed adolescent pregnancy, smoking, eclampsia, bacterial vaginosis, LC-PUFA, placental vitamin D, and several minerals as the significant determinants of preterm birth in urban Indonesia.

Pre-pregnancy body mass index and low birthweight: Secondary data analysis using health insurance claims data in Japan.

AIM: For women, being underweight increases their susceptibility to osteoporosis, anemia, and other conditions and affects the weight of their infants and the well-being of future generations. This study examined the association between low pre-pregnancy body mass index (BMI) and low birthweight using health insurance claims data and health checkup data, including weight measurements. METHODS: We used health insurance claims data and health checkup data (JMDC, Tokyo, Japan) of women and their newborns in Japan between 2006 and 2020. We used checkup data, which included more accurate weight measurements and blood test-based diagnoses of anemia and hyperlipidemia compared to self-reported data. Maternal pre-pregnancy BMI was compared across three groups: underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), and overweight (BMI ≥25.0 kg/m2). The primary outcome was low birthweight (<2500 g), and secondary outcome was preterm childbirth. Logistic regression analyses were conducted to compare outcomes in the three groups by BMI. The underweight BMI group was considered as the reference group. A subgroup analysis was performed by maternal age. RESULTS: In total, 16 363 mothers (underweight, 3418 [21%], normal weight, 11 493 [70%], and overweight, 1452 [8.9%]) were included. The risk of primary outcome (low birthweight) was significantly lower in the normal weight group than in the underweight group (4.6% vs. 5.7%; adjusted odds ratio 0.78 [95% confidence interval: 0.65-0.96]). In the subgroup analyses, no significant differences were noted in the incidences of low birthweight and preterm childbirth between maternal age groups. CONCLUSIONS: Pre-pregnancy BMI was associated with an increased risk of delivering low-birthweight infant. Awareness about the importance of women's pre-pregnancy health and appropriate BMI may reduce the incidence of low birthweight.

Does Dietitian Involvement During Pregnancy Improve Birth Outcomes? A Systematic Review.

Maternal diet during pregnancy can have a significant impact on maternal and offspring health. As nutrition counselling is an important component of prenatal care, registered dietitians (RDs) are uniquely trained professionals who can provide personalized nutrition counselling customized to an individual's sociocultural needs. The objective of this systematic review was to determine if RD involvement during pregnancy is associated with a lower prevalence of adverse birth outcomes in the United States and Canada. The review was conducted through a search of four databases: PubMed, CINAHL, Embase, and Web of Science. A total of 14 studies were identified. Women had a lower prevalence of low birth weight and preterm infants when RDs were involved during prenatal care. While RD involvement during pregnancy was not associated with macrosomia, more research is needed to assess its relationship with small for gestational age, large for gestational age, and infant mortality. Future research should also investigate the specific dietary advice provided by RDs and the extent and timing of their involvement throughout pregnancy to better understand the mechanisms surrounding nutrition counselling, in utero development, and health outcomes.

Maternal Eating Disorders and Adverse Birth Outcomes: A Systematic Review and Meta-Analysis.

Previous systematic reviews have reported on the relationship between eating disorders (EDs) and birth outcomes, but there are no existing meta-analyses on this topic. This systematic review and meta-analysis examines the association between lifetime maternal EDs, including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) with low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), large for gestational age (LGA), and miscarriage. Four databases were systematically searched for quantitative literature on maternal EDs that preceded birth outcomes. Eighteen studies met the inclusion criteria and were included in the review. The meta-analyses included 6 studies on miscarriage, 11 on PTB, 4 on LBW, 9 on SGA, and 4 on LGA. The Mantel-Haenszel random effects model was used to test the associations between EDs and birth outcomes. The results showed significant positive associations between AN and LBW (OR 1.74, 95% confidence interval (CI) 1.49, 2.03), AN and SGA (OR 1.39, 95% CI 1.17, 1.65), BN and PTB (OR 1.19, 95% CI 1.04, 1.36), and BED and LGA (OR 1.43 95% CI 1.18, 1.72). EDs were not significantly correlated with miscarriage. These findings reveal the importance of screening for and treating EDs in pregnant women.

Evaluation of possible associated factors for early childhood caries: are preterm birth and birth weight related?

BACKGROUND: This study aimed to evaluate the oral and dental health of preschool children aged 12-71 months living in the Eastern Anatolia Region of Turkey, and to examine the effects of low birth weight (LBW) and preterm, early term and term birth on dental caries. METHODS: 475 participants were included in the study. Intraoral examinations were performed and evaluated for the presence of early childhood caries (ECC). These values ​​are; Relationships such as age, gender, birth weight, week of birth, tooth brushing frequency, cariogenic nutrition, and parental education levels were examined. The obtained data were analyzed statistically (chi-square, t-test, artificial neural network (ANN)). RESULTS: Of the 475 participants, whose parents agreed to fill out the questionnaire, 250 were female and 225 were male. While the mean age was 49.78 ± 14.78 months for those with ECC, it was 38.93 ± 17.96 months for those without. Higher duration of breastfeeding (p = 0.04), education level of parents (p = 0.001), lower socioeconomic level (p = 0.001), and lower brushing frequency (p = 0.001) were also found to be significantly associated with ECC. ECC was seen in 90% of 77 children with a history of preterm birth. In LBW, this rate was 83%. According to the ANN result, in preterm birth; 12.9% affected ECC by LBW. CONCLUSION: According to the results of our study, both LBW and preterm delivery were found to be associated with ECC and S-ECC (severe early childhood caries). An additional study on parents of preterm/LBW infants would be beneficial. In the early period, regular dental examination, implementation of preventive and preventive treatments, and nutrition education to parents can make a significant difference in the prevention of ECC.

[Correlations of Birth Defects With Birth Weight and Gestational Age].

Objective To analyze the incidence rate of birth defects in infants born at different gestational ages and birth weights,so as to provide a basis for improving the surveillance system and reducing the incidence of birth defects. Methods Data of all perinatal infants born at and after 28 weeks of gestation and within 7 days after delivery in all the hospitals with the obstetrical department from October 1,2003 to September 30,2015 were collected. Results From 2003 to 2015,1 236 937 perinatal infants were monitored,including 10 619 with birth defects (incidence rate of 8.59‰).Among the infants with birth defects identified by the hospital surveillance system of birth defects in Xi'an during the study period,3 306,3 473,and 224 infants showed the birth weights less than 2 500 g,the gestational age within the range of [28,37] weeks,and the gestation age≥42 weeks,respectively.The low birth weight infants showed higher incidence rate of birth defects than the normal birth weight infants (χ2=37 097.79,P<0.001).The premature infants (gestational age<37 weeks) and postterm infants (gestational age≥42 weeks) showed higher incidence rates of birth defects than infants born at normal gestational age (χ2=24 998.24,P<0.001;χ2=196.40,P<0.001).The top five birth defects of low birth weight infants were congenital hydrocephalus,spina bifida,congenital heart disease,anencephaly,and cleft lip and cleft palate.The outcomes of birth defects in normal weight infants and low weight infants were mainly live births (68.60%) and stillbirths (54.72%),respectively,which showed a significant difference (χ2=647.59,P<0.001).The main outcomes of birth defects in the infants born at normal gestation age,postterm infants,and premature infants were mainly live births (77.38%),live births (83.93%),and stillbirths (57.79%),respectively,which showed significant differences (premature infants vs.infants born at normal gestation age: χ2=2 025.08,P<0.001;premature infants vs. postterm infants:χ2=245.39,P<0.001;infants born at normal gestation age vs.postterm infants:χ2=16.28,P=0.001). Conclusions Premature infants,low birth weight infants,and postterm infants showed significantly higher incidence rate of birth defects than the infants born at normal gestation age.The outcomes of birth defects had significant differences between low birth weight infants and normal birth weight infants,between premature infants and infants born at normal gestation age,between premature infants and postterm infants,and between infants born at normal gestation age and postterm infants.

Impaired cerebrovascular CO2 reactivity at high altitude in prematurely born adults.

Premature birth impairs cardiac and ventilatory responses to both hypoxia and hypercapnia, but little is known about cerebrovascular responses. Both at sea level and after 2 days at high altitude (3375 m), 16 young preterm-born (gestational age, 29 ± 1 weeks) and 15 age-matched term-born (40 ± 0 weeks) adults were exposed to two consecutive 4 min bouts of hyperoxic hypercapnic conditions (3% CO2 -97% O2 ; 6% CO2 -94% O2 ), followed by two periods of voluntary hyperventilation-induced hypocapnia. We measured middle cerebral artery blood velocity, end-tidal CO2 , pulmonary ventilation, beat-by-beat mean arterial pressure and arterialized capillary blood gases. Baseline middle cerebral artery blood velocity increased at high altitude compared with sea level in term-born (+24 ± 39%, P = 0.036), but not in preterm-born (-4 ± 27%, P = 0.278) adults. The end-tidal CO2 , pulmonary ventilation and mean arterial pressure were similar between groups at sea level and high altitude. Hypocapnic cerebrovascular reactivity was higher at high altitude compared with sea level in term-born adults (+173 ± 326%, P = 0.026) but not in preterm-born adults (-21 ± 107%, P = 0.572). Hypercapnic reactivity was altered at altitude only in preterm-born adults (+125 ± 144%, P < 0.001). Collectively, at high altitude, term-born participants showed higher hypocapnic (P = 0.012) and lower hypercapnic (P = 0.020) CO2 reactivity compared with their preterm-born peers. In conclusion, exposure to high altitude revealed different cerebrovascular responses in preterm- compared with term-born adults, despite similar ventilatory responses. These findings suggest a blunted cerebrovascular response at high altitude in preterm-born adults, which might predispose these individuals to an increased risk of high-altitude illnesses. KEY POINTS: Cerebral haemodynamics and cerebrovascular reactivity in normoxia are known to be similar between term-born and prematurely born adults. In contrast, acute exposure to high altitude unveiled different cerebrovascular responses to hypoxia, hypercapnia and hypocapnia. In particular, cerebral vasodilatation was impaired in prematurely born adults, leading to an exaggerated cerebral vasoconstriction. Cardiovascular and ventilatory responses to both hypo- and hypercapnia at sea level and at high altitude were similar between control subjects and prematurely born adults. Other mechanisms might therefore underlie the observed blunted cerebral vasodilatory responses in preterm-born adults at high altitude.

Indirect evidence for altered dopaminergic neurotransmission in very premature-born adults.

While animal models indicate altered brain dopaminergic neurotransmission after premature birth, corresponding evidence in humans is scarce due to missing molecular imaging studies. To overcome this limitation, we studied dopaminergic neurotransmission changes in human prematurity indirectly by evaluating the spatial co-localization of regional alterations in blood oxygenation fluctuations with the distribution of adult dopaminergic neurotransmission. The study cohort comprised 99 very premature-born (<32 weeks of gestation and/or birth weight below 1500 g) and 107 full-term born young adults, being assessed by resting-state functional MRI (rs-fMRI) and IQ testing. Normative molecular imaging dopamine neurotransmission maps were derived from independent healthy control groups. We computed the co-localization of local (rs-fMRI) activity alterations in premature-born adults with respect to term-born individuals to different measures of dopaminergic neurotransmission. We performed selectivity analyses regarding other neuromodulatory systems and MRI measures. In addition, we tested if the strength of the co-localization is related to perinatal measures and IQ. We found selectively altered co-localization of rs-fMRI activity in the premature-born cohort with dopamine-2/3-receptor availability in premature-born adults. Alterations were specific for the dopaminergic system but not for the used MRI measure. The strength of the co-localization was negatively correlated with IQ. In line with animal studies, our findings support the notion of altered dopaminergic neurotransmission in prematurity which is associated with cognitive performance.

Maternal multimorbidity and preterm birth in Scotland: an observational record-linkage study.

BACKGROUND: Multimorbidity is common in women across the life course. Preterm birth is the single biggest cause of neonatal mortality and morbidity. We aim to estimate the prevalence of multimorbidity in pregnant women and to examine the association between maternal multimorbidity and PTB. METHODS: This is a retrospective cohort study using electronic health records from the Scottish Morbidity Records. All pregnancies among women aged 15 to 49 with a conception date between 1 January 2014 and 31 December 2018 were included. Multimorbidity was defined as the presence of two or more pre-existing long-term physical or mental health conditions, and complex multimorbidity as the presence of four or more. It was calculated at the time of conception using a predefined list of 79 conditions published by the MuM-PreDiCT consortium. PTB was defined as babies born alive between 24 and less than 37 completed weeks of gestation. We used Generalised Estimating Equations adjusted for maternal age, socioeconomic status, number of previous pregnancies, BMI, and smoking history to estimate the effect of maternal pre-existing multimorbidity. Absolut rates are reported in the results and tables, whilst Odds Ratios (ORs) are adjusted (aOR). RESULTS: Thirty thousand five hundred fifty-seven singleton births from 27,711 pregnant women were included in the analysis. The prevalence of pre-existing multimorbidity and complex multimorbidity was 16.8% (95% CI: 16.4-17.2) and 3.6% (95% CI: 3.3-3.8), respectively. The prevalence of multimorbidity in the youngest age group was 10.2%(95% CI: 8.8-11.6), while in those 40 to 44, it was 21.4% (95% CI: 18.4-24.4), and in the 45 to 49 age group, it was 20% (95% CI: 8.9-31.1). In women without multimorbidity, the prevalence of PTB was 6.7%; it was 11.6% in women with multimorbidity and 15.6% in women with complex multimorbidity. After adjusting for maternal age, socioeconomic status, number of previous pregnancies, Body Mass Index (BMI), and smoking, multimorbidity was associated with higher odds of PTB (aOR = 1.64, 95% CI: 1.48-1.82). CONCLUSIONS: Multimorbidity at the time of conception was present in one in six women and was associated with an increased risk of preterm birth. Multimorbidity presents a significant health burden to women and their offspring. Routine and comprehensive evaluation of women with multimorbidity before and during pregnancy is urgently needed.

Extended Risk of Mortality in Children with Inborn Errors of Metabolism: A Longitudinal Cohort Study.

OBJECTIVES: To determine the long-term risk of mortality among children with inborn errors of metabolism. STUDY DESIGN: We conducted a retrospective cohort study of 1750 children with inborn errors of metabolism (excluding mitochondrial disorders) and 1 036 668 children without errors of metabolism who were born in Quebec, Canada, between 2006 and 2019. Main outcome measures included all-cause and cause-specific mortality between birth and 14 years of age. We used adjusted survival regression models to estimate HRs and 95% CIs for the association between inborn errors of metabolism and mortality over time. RESULTS: Mortality rates were greater for children with errors of metabolism than for unaffected children (69.1 vs 3.2 deaths per 10 000 person-years). During 7 702 179 person-years of follow-up, inborn errors of metabolism were associated with 21.2 times the risk of mortality compared with no error of metabolism (95% CI 17.23-26.11). Disorders of mineral metabolism were associated with greater mortality the first 28 days of life (HR 60.62, 95% CI 10.04-365.98), and disorders of sphingolipid metabolism were associated with greater mortality by 1 year (HR 284.73, 95% CI 139.20-582.44) and 14 years (HR 1066.00, 95% CI 298.91-3801.63). Errors of metabolism were disproportionately associated with death from hepatic/digestive (HR 208.21, 95% CI 90.28-480.22), respiratory (HR 116.57, 95% CI 71.06-191.23), and infectious causes (HR 119.83, 95% CI 40.56-354.04). CONCLUSIONS: Children with errors of metabolism have a considerably elevated risk of mortality before 14 years, including death from hepatic/digestive, respiratory, and infectious causes. Targeting these causes of death may help improve long-term survival.

Effect of Presenting Survival Information as Text or Pictograph During Periviable Birth Counseling: A Randomized, Controlled Trial.

OBJECTIVES: To examine whether presenting a 30% or a 60% chance of survival in different survival information formats would influence hypothetical periviable birth treatment choice and whether treatment choice would be associated with participants' recall or their intuitive beliefs about the chances of survival. STUDY DESIGN: An internet sample of women (n = 1052) were randomized to view a vignette with either a 30% or 60% chance of survival with intensive care during the periviable period. Participants were randomized to survival information presented as text-only, in a static pictograph, or in an iterative pictograph. Participants chose intensive care or palliative care and reported their recall of the chance of survival and their intuitive beliefs about their infant's chance of survival. RESULTS: There was no difference in treatment choice by presentation with a 30% vs 60% chance of survival (P = .48), by survival information format (P = .80), or their interaction (P = .18). However, participants' intuitive beliefs about chance of survival significantly predicted treatment choice (P < .001) and had the most explanatory power of any participant characteristic. Intuitive beliefs were optimistic and did not differ by presentation of a 30% or 60% chance of survival (P = .65), even among those with accurate recall of the chance of survival (P = .09). CONCLUSIONS: Physicians should recognize that parents may use more than outcome data to make treatment choices and in forming their own, often-optimistic, intuitive beliefs about their infant's chance of survival. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04859114.