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One of the United Nations' Millennium Development Goals of 2000 was to reduce maternal mortality by 75% in 15 y; however, this challenge was not met by many industrialized countries. As average maternal age continues to rise in these countries, associated potentially life-threatening severe maternal morbidity has been understudied. Our primary objective was to examine the associations between maternal age and severe maternal morbidities. The secondary objective was to compare these associations with those for adverse fetal/infant outcomes. This was a population-based retrospective cohort study, including all singleton births to women residing in Washington State, US, 1 January 2003-31 December 2013 (n = 828,269). We compared age-specific rates of maternal mortality/severe morbidity (e.g., obstetric shock) and adverse fetal/infant outcomes (e.g., perinatal death). Logistic regression was used to adjust for parity, body mass index, assisted conception, and other potential confounders. We compared crude odds ratios (ORs) and adjusted ORs (AORs) and risk differences and their 95% CIs. Severe maternal morbidity was significantly higher among teenage mothers than among those 25-29 y (crude OR = 1.5, 95% CI 1.5-1.6) and increased exponentially with maternal age over 39 y, from OR = 1.2 (95% CI 1.2-1.3) among women aged 35-39 y to OR = 5.4 (95% CI 2.4-12.5) among women aged ≥50 y. The elevated risk of severe morbidity among teen mothers disappeared after adjustment for confounders, except for maternal sepsis (AOR = 1.2, 95% CI 1.1-1.4). Adjusted rates of severe morbidity remained increased among mothers ≥35 y, namely, the rates of amniotic fluid embolism (AOR = 8.0, 95% CI 2.7-23.7) and obstetric shock (AOR = 2.9, 95% CI 1.3-6.6) among mothers ≥40 y, and renal failure (AOR = 15.9, 95% CI 4.8-52.0), complications of obstetric interventions (AOR = 4.7, 95% CI 2.3-9.5), and intensive care unit (ICU) admission (AOR = 4.8, 95% CI 2.0-11.9) among those 45-49 y. The adjusted risk difference in severe maternal morbidity compared to mothers 25-29 y was 0.9% (95% CI 0.7%-1.2%) for mothers 40-44 y, 1.6% (95% CI 0.7%-2.8%) for mothers 45-49 y, and 6.4% for mothers ≥50 y (95% CI 1.7%-18.2%). Similar associations were observed for fetal and infant outcomes; neonatal mortality was elevated in teen mothers (AOR = 1.5, 95% CI 1.2-1.7), while mothers over 29 y had higher risk of stillbirth. The rate of severe maternal morbidity among women over 49 y was higher than the rate of mortality/serious morbidity of their offspring. Despite the large sample size, statistical power was insufficient to examine the association between maternal age and maternal death or very rare severe morbidities. Maternal age-specific incidence of severe morbidity varied by outcome. Older women (≥40 y) had significantly elevated rates of some of the most severe, potentially life-threatening morbidities, including renal failure, shock, acute cardiac morbidity, serious complications of obstetric interventions, and ICU admission. These results should improve counselling to women who contemplate delaying childbirth until their forties and provide useful information to their health care providers. This information is also useful for preventive strategies to lower maternal mortality and severe maternal morbidity in developed countries.

Few studies have examined the associations between sleep duration, shiftwork, and exercise to the infrequent menstruation, hyperandrogenism, and ovarian morphological changes observed in women with polycystic ovarian syndrome (PCOS). To examine whether lifestyle factors, including short sleep duration, insufficient exercise, and shiftwork, alone or in combination, are associated with the reproductive and metabolic abnormalities typical of PCOS in a healthy population. Prospective cross-sectional study of 231 women, including healthcare workers recruited for an annual health screen, healthy referral patients from the Women's Clinic and volunteers from the university community at the National University Hospital, Singapore, from 2011 to 2015. The women completed a questionnaire, including their menstrual cycle length, sleep length, frequency of exercise and shift work. Hyperandrogenism (hirsutism score, testosterone, sex hormone binding globulin (SHBG)), ovarian morphology and function (anthral follicle count, ovarian volume, anti-mullerian hormone (AMH)), and metabolic measures (body mass index (BMI), waist hip ratio (WHR), blood pressure, fasting glucose, fasting insulin and fasting lipids) were examined through anthropometric measurements, transvaginal ultrasound scans, and blood tests. No significant associations were observed between shift work, exercise or sleep duration and the androgenic and ovarian measures that define PCOS. However, women reporting fewer than 6 hours of sleep were more likely to report abnormal (short or long) menstrual cycle lengths (OR = 2.1; 95% CI, 1.1 to 4.2). Women who reported fewer than 6 hours of sleep had increased fasting insulin levels (difference in means = 2.13; 95% CI, 0.27 to 3.99 mU/L) and higher odds of insulin resistance (OR = 2.58; CI, 1.16 to 5.76). Lack of regular exercise was associated with higher mean fasting insulin (difference in means = 2.3 mU/L; 95% CI, 0.5 to 4.1) and HOMA-IR (difference in means = 0.49; 95% CI, 0.09 to 0.90) levels. Women with insufficient sleep are at increased risk of menstrual disturbances and insulin resistance, but do not have the hyperandrogenism and polycystic ovarian morphology typical of PCOS. Improved sleep duration may help reduce the risks of diabetes or infertility. Shift work, exercise or sleep duration appear not to impact the androgenic and ovarian measures that define PCOS.

In a Perspective, Sarka Lisonkova and Michael Kramer discuss the accompanying study by Kathryn Fitzpatrick and co-authors on management of amniotic fluid embolism.In a Perspective, Sarka Lisonkova and Michael Kramer discuss the accompanying study by Kathryn Fitzpatrick and co-authors on management of amniotic fluid embolism.

Abstract Study Objectives: To examine the influence of maternal sleep quality and nocturnal sleep duration on risk of gestational diabetes mellitus (GDM) in a multiethnic Asian population. Methods: A cohort of 686 women (376 Chinese, 186 Malay, and 124 Indian) with a singleton pregnancy attended a clinic visit at 26–28 weeks of gestation as part of the Growing Up in Singapore Towards healthy Outcomes mother–offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). GDM was diagnosed based on a 75-g oral glucose tolerance test administered after an overnight fast (1999 WHO criteria). Multiple logistic regression was used to model separately the associations of poor sleep quality (PSQI score > 5) and short nocturnal sleep duration (<6 h) with GDM, adjusting for age, ethnicity, maternal education, body mass index, previous history of GDM, and anxiety (State-Trait Anxiety Inventory score). Results: In the cohort 296 women (43.1%) had poor sleep quality and 77 women (11.2%) were categorized as short sleepers; 131 women (19.1%) were diagnosed with GDM. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of GDM (poor sleep, adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.11 to 2.76; short sleep, adjusted OR = 1.96, 95% CI 1.05 to 3.66). Conclusions: During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibited abnormal glucose regulation. Treating sleep problems and improving sleep behavior in pregnancy could potentially reduce the risk and burden of GDM.

Evidence on the long-term effect of breastfeeding on neurocognitive development is based almost exclusively on observational studies. In the 16-year follow-up study of a large, cluster-randomized trial of a breastfeeding promotion intervention, we evaluated the long-term persistence of the neurocognitive benefits of the breastfeeding promotion intervention previously observed at early school age. A total of 13,557 participants (79.5% of the 17,046 randomized) of the Promotion of Breastfeeding Intervention Trial (PROBIT) were followed up at age 16 from September 2012 to July 2015. At the follow-up, neurocognitive function was assessed in 7 verbal and nonverbal cognitive domains using a computerized, self-administered test battery among 13,427 participants. Using an intention-to-treat (ITT) analysis as our prespecified primary analysis, we estimated cluster- and baseline characteristic-adjusted mean differences between the intervention (prolonged and exclusive breastfeeding promotion modelled on the Baby-Friendly Hospital Initiative) and control (usual care) groups in 7 cognitive domains and a global cognitive score. In our prespecified secondary analysis, we estimated mean differences by instrumental variable (IV) analysis to account for noncompliance with the randomly assigned intervention and estimate causal effects of breastfeeding. The 16-year follow-up rates were similar in the intervention (79.7%) and control groups (79.3%), and baseline characteristics were comparable between the two. In the cluster-adjusted ITT analyses, children in the intervention group did not show statistically significant differences in the scores from children in the control group. Prespecified additional adjustment for baseline characteristics improved statistical precision and resulted in slightly higher scores among children in the intervention for verbal function (1.4 [95% CI 0.3-2.5]) and memory (1.2 [95% CI 0.01-2.4]). IV analysis showed that children who were exclusively breastfed for ≥3 (versus <3) months had a 3.5-point (95% CI 0.9-6.1) higher verbal function, but no differences were observed in other domains. While our computerized, self-administered cognitive testing reduced the cluster-level variability in the scores, it may have increased individual-level measurement errors in adolescents. We observed no benefit of a breastfeeding promotion intervention on overall neurocognitive function. The only beneficial effect was on verbal function at age 16. The higher verbal ability is consistent with results observed at early school age; however, the effect size was substantially smaller in adolescence. ClinicalTrials.gov NCT01561612.

Operative vaginal delivery (OVD) is considered safe if carried out by trained personnel. However, opportunities for training in OVD have declined and, given these shifts in practice, the safety of OVD is unknown. We estimated incidence rates of trauma following OVD in Canada, and quantified variation in trauma rates by instrument, region, level of obstetric care and institutional OVD volume. We conducted a cohort study of all singleton, term deliveries in Canada between April 2013 and March 2019, excluding Quebec. Our main outcome measures were maternal trauma (e.g., obstetric anal sphincter injury, high vaginal lacerations) and neonatal trauma (e.g., subgaleal hemorrhage, brachial plexus injury). We calculated adjusted and stabilized rates of trauma using mixed-effects logistic regression. Of 1 326 191 deliveries, 38 500 (2.9%) were attempted forceps deliveries and 110 987 (8.4%) were attempted vacuum deliveries. The maternal trauma rate following forceps delivery was 25.3% (95% confidence interval [CI] 24.8%–25.7%) and the neonatal trauma rate was 9.6 (95% CI 8.6–10.6) per 1000 live births. Maternal and neonatal trauma rates following vacuum delivery were 13.2% (95% CI 13.0%–13.4%) and 9.6 (95% CI 9.0–10.2) per 1000 live births, respectively. Maternal trauma rates remained higher with forceps than with vacuum after adjustment for confounders (adjusted rate ratio 1.70, 95% CI 1.65–1.75) and varied by region, but not by level of obstetric care. In Canada, rates of trauma following OVD are higher than previously reported, irrespective of region, level of obstetric care and volume of OVD among hospitals. These results support a reassessment of OVD safety in Canada.

Analyze the relation of gestational diabetes and maternal blood glucose levels to early cognitive functions in the first two years of life. In a prospective Singaporean birth cohort study, pregnant women were screened for gestational diabetes at 26-28 weeks gestation using a 75-g oral glucose tolerance test. Four hundred and seventy three children (n = 74 and n = 399 born to mothers with and without gestational diabetes respectively) underwent neurocognitive assessments at 6, 18, and/or 24 month, including electrophysiology during an attentional task and behavioral measures of attention, memory and cognition. Gestational diabetes is related to left hemisphere EPmax amplitude differences (oddball versus standard) at both six (P = 0.039) and eighteen months (P = 0.039), with mean amplitudes suggesting offspring of mothers with gestational diabetes exhibit greater neuronal activity to standard stimuli and less to oddball stimuli. Associations between 2-hour maternal glucose levels and the difference in EPmax amplitude were marginal at 6 months [adjusted β = -0.19 (95% CI: -0.42 to +0.04) μV, P = 0.100] and significant at 18 months [adjusted β = -0.27 (95% CI: -0.49 to -0.06) μV, P = 0.014], and the EPmax amplitude difference (oddball-standard) associated with the Bayley Scales of Infant and toddler Development-III cognitive score at 24 months [β = 0.598 (95% CI: 0.158 to 1.038), P = 0.008]. Gestational diabetes and maternal blood glucose levels are associated with offspring neuronal activity during an attentional task at both six and eighteen months. Such electrophysiological differences are likely functionally important, having been previously linked to attention problems later in life.

Women are less likely to have classic cardiovascular risk factors than men, and events during their reproductive and menopausal years may increase hypertension risk. The aim of this study is to examine woman-specific factors, including menstrual, reproductive and pregnancy complications, in relation to the prevalence of hypertension in mid-life Asian women. This is a cross-sectional study of 1146 healthy women aged 45-69 years, from a multi-ethnic Asian cohort. The women completed an extensive questionnaire that included their sociodemographic details, medical history, lifestyle and physical activity, and reproductive and menopausal history. They also underwent objectively measured physical performance tests and a dual X-ray absorptiometry scan. Hypertension was defined as a systolic BP ≥140 and/or diastolic BP ≥90mm Hg, past diagnosis by a physician, or use of antihypertensive medications. Multivariable logistic regression was used to assess the independent risk factors for hypertension. The average age of the 1146 women analysed was 56.3 (SD 6.2) years, and 55.2 percent of them were hypertensive. The prevalence of gestational diabetes and gestational hypertension was 12.6% and 9.4%, respectively. Besides age, abnormal menstrual cycle length at 25 years of age (OR:2.35, CI:1.34-4.13), preeclampsia (OR:2.46, CI:1.06-5.74), increased visceral adiposity (OR:4.21, CI:2.28-7.79) and reduced physical performance (OR:2.83, CI:1.46-5.47) were independently associated with hypertension in Asian women. Our findings highlight the necessity of including features of menstrual and reproductive history as possible indicators of hypertension risk in cardiovascular disease risk assessment and prevention among Asian women. Reducing visceral adiposity and exercise to improve physical performance may help women avoid developing hypertension.

Background Higher screen viewing time (SVT) in childhood has been associated with adverse health outcomes, but the predictors of SVT in early childhood are poorly understood. We examined the sociodemographic and behavioral predictors of total and device-specific SVT in a Singaporean cohort. Methods At ages 2 and 3 years, SVT of 910 children was reported by their parents. Interviewer-administered questionnaires assessed SVT on weekdays and weekends for television, computer, and hand-held devices. Multivariable linear mixed-effect models were used to examine the associations of total and device-specific SVT at ages 2 and 3 with predictors, including children’s sex, ethnicity, birth order, family income, and parental age, education, BMI, and television viewing time. Results At age 2, children’s total SVT averaged 2.4 ± 2.2 (mean ± SD) hours/day, including 1.6 ± 1.6 and 0.7 ± 1.0 h/day for television and hand-held devices, respectively. At age 3, hand-held device SVT was 0.3 (95% CI: 0.2, 0.4) hours/day higher, while no increases were observed for other devices. SVT tracked moderately from 2 to 3 years ( r  = 0.49, p  < 0.0001). Compared to Chinese children, Malay and Indian children spent 1.04 (0.66, 1.41) and 0.54 (0.15, 0.94) more hours/day watching screens, respectively. Other predictors of longer SVT were younger maternal age, lower maternal education, and longer parental television time. Conclusions In our cohort, the main predictors of longer children’s SVT were Malay and Indian ethnicity, younger maternal age, lower education and longer parental television viewing time. Our study may help target populations for future interventions in Asia, but also in other technology-centered societies. Trial registration This ongoing study was first registered on July 1, 2010 on NCT01174875 as. Retrospectively registered.

Macrophages promote tissue remodeling but few mechanisms exist to modulate their activity during tissue fibrosis. Serum amyloid P (SAP), a member of the pentraxin family of proteins, signals through Fcgamma receptors which are known to affect macrophage activation. We determined that IPF/UIP patients have increased protein levels of several alternatively activated pro-fibrotic (M2) macrophage-associated proteins in the lung and monocytes from these patients show skewing towards an M2 macrophage phenotype. SAP therapeutically inhibits established bleomycin-induced pulmonary fibrosis, when administered systemically or locally to the lungs. The reduction in aberrant collagen deposition was associated with a reduction in M2 macrophages in the lung and increased IP10/CXCL10. These data highlight the role of macrophages in fibrotic lung disease, and demonstrate a therapeutic action of SAP on macrophages which may extend to many fibrotic indications caused by over-exuberant pro-fibrotic macrophage responses.