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Improvement of water and sanitation conditions may reduce infant mortality, particularly in countries like India where open defecation is highly prevalent. We conducted a quasi-experimental study to investigate the association between the Swachh Bharat Mission (SBM)-a national sanitation program initiated in 2014-and infant (IMR) and under five mortality rates (U5MR) in India. We analyzed data from thirty-five Indian states and 640 districts spanning 10 years (2011-2020), with IMR and U5MR per thousand live births as the outcomes. Our main exposure was the district-level annual percentage of households that received a constructed toilet under SBM. We mapped changes in IMR and U5MR and toilet access at the district level over time. We fit two-way fixed effects regression models controlling for sociodemographic, wealth, and healthcare-related confounders at the district-level to estimate the association between toilets constructed and child mortality. Toilet access and child mortality have a historically robust inverse association in India. Toilets constructed increased dramatically across India following the implementation of SBM in 2014. Results from panel data regression models show that districts with > 30% toilets constructed under SBM corresponds with 5.3 lower IMR (p

ObjectiveTo test the effect of proactive home visits by trained community health workers (CHWs) on child survival.MethodsWe conducted a two arm, parallel, unmasked cluster-randomized trial in 137 village-clusters in rural Mali. From February 2017 to January 2020, 31 761 children enrolled at the trial start or at birth. Village-clusters received either primary care services by CHWs providing regular home visits (intervention) or by CHWs providing care at a fixed site (control). In both arms, user fees were removed and primary health centres received staffing and infrastructure improvements before trial start. Using lifetime birth histories from women aged 15-49 years surveyed annually, we estimated incidence rate ratios (IRR) for intention-to-treat and per-protocol effects on under-five mortality using Poisson regression models.FindingsOver three years, we observed 52 970 person-years (27 332 in intervention arm; 25 638 in control arm). During the trial, 909 children in the intervention arm and 827 children in the control arm died. The under-five mortality rate declined from 142.8 (95% CI: 133.3-152.9) to 56.7 (95% CI: 48.5-66.4) deaths per 1000 live births in the intervention arm; and from 154.3 (95% CI: 144.3-164.9) to 54.9 (95% CI: 45.2-64.5) deaths per 1000 live births in the control arm. Intention-to-treat (IRR: 1.02; 95% CI: 0.88-1.19) and per-protocol estimates (IRR: 1.01; 95% CI: 0.87-1.18) showed no difference between study arms.ConclusionThough proactive home visits did not reduce under-five mortality, system-strengthening measures may have contributed to the decline in under-five mortality in both arms.

Exposure to high and low ambient temperatures increases the risk of neonatal mortality, but the contribution of climate change to temperature-related neonatal deaths is unknown. We use Demographic and Health Survey (DHS) data (n = 40,073) from 29 low- and middle-income countries to estimate the temperature-related burden of neonatal deaths between 2001 and 2019 that is attributable to climate change. We find that across all countries, 4.3% of neonatal deaths were associated with non-optimal temperatures. Climate change was responsible for 32% (range: 19-79%) of heat-related neonatal deaths, while reducing the respective cold-related burden by 30% (range: 10-63%). Climate change has impacted temperature-related neonatal deaths in all study countries, with most pronounced climate-induced losses from increased heat and gains from decreased cold observed in countries in sub-Saharan Africa. Future increases in global mean temperatures are expected to exacerbate the heat-related burden, which calls for ambitious mitigation and adaptation measures to safeguard the health of newborns.

This study examines the association between antenatal care (ANC) attendance and infant mortality and growth outcomes. The study used data from the Nouveux-nés et Azithromycine: une Innovation dans le Traitement des Enfants (NAITRE) trial conducted in Burkina Faso. This analysis included 21,795 neonates aged 8 to 27 days who were enrolled in the trial and had ANC data available. Infants were followed until 6 months of age. The analysis adjusted for potential confounders including infants sex, maternal age, education, urbanicity, geographic region, season (dry versus rainy), pregnancy type (singleton versus multiple), number of previous pregnancies, if the infant was breastfed, and if the facility had an onsite physician to account for level of care. We used logistic and linear regression models to evaluate the association between ANC visits and all-cause infant mortality and infant growth measurements at 6 months. There was no significant association between ANC visits and 6-month mortality. Higher ANC attendance was associated with improved growth outcomes in infants at 6 months of age. After adjusting for potential confounders, each additional ANC visit was associated with a 0.03 kg increase in mean weight, 0.07 cm increase in mean length, 0.04 SD increase in mean mid-upper-arm circumference, 0.04 SD increase in mean height-for-age, 0.04 SD mean weight-for-age, and 0.02 SD mean weight-for-length Z-scores. These mean differences were statistically significant (except for weight-for-length Z-scores) but may not be clinically meaningful. Further research is warranted to explore the relationship between ANC attendance and longer-term health outcomes among infants.

OBJECTIVE: Most evidence supporting screening for undernutrition is for children aged 6-59 months. However, the highest risk of mortality and highest incidence of wasting occurs in the first 6 months of life. We evaluated relationships between neonatal anthropometric indicators, including birth weight, weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ) and mid-upper arm circumference (MUAC) and mortality and growth at 6 months of age among infants in Burkina Faso. DESIGN: Data arose from a randomised controlled trial evaluating neonatal azithromycin administration for the prevention of child mortality. We evaluated relationships between baseline anthropometric measures and mortality, wasting (WLZ < -2), stunting (LAZ < -2) and underweight (WAZ < -2) at 6 months of age were estimated using logistic regression models adjusted for the childs age and sex. SETTING: Five regions of Burkina Faso. PARTICIPANTS: Infants aged 8-27 d followed until 6 months of age. RESULTS: Of 21 832 infants enrolled in the trial, 7·9 % were low birth weight (

BACKGROUND: Antenatal care (ANC) is critical to reducing maternal and infant mortality. However, sub-Saharan Africa (SSA) continues to have among the lowest levels of ANC receipt globally, with half of mothers not meeting the WHO minimum recommendation of at least four visits. Increasing ANC coverage will require not only directly reducing geographic and financial barriers to care but also addressing the social determinants of health that shape access. Among those with the greatest potential for impact is maternal education: past research has documented a relationship between higher educational attainment and antenatal healthcare access, as well as related outcomes like health literacy and autonomy in health decision-making. Yet little causal evidence exists about whether changing educational policies can improve ANC coverage. This study fills this research gap by investigating the impact of national-level policies that eliminate tuition fees for lower secondary education in SSA on the number of ANC visits. METHODS: To estimate the effect of womens exposure to tuition-free education policies at the primary and lower secondary levels on their ANC visits, a difference-in-difference methodology was employed. This analysis leverages the variation in the timing of education policies across nine SSA countries. RESULTS: Exposure to tuition-free primary and lower secondary education is associated with improvements in the number of ANC visits, increasing the share of women meeting the WHO recommendation of at least four ANC visits by 6-14%. Moreover, the impact of both education policies combined is greater than that of tuition-free primary education alone. However, the effects vary across individual treatment countries, suggesting the need for further investigation into country-specific dynamics. CONCLUSIONS: The findings of this study have significant implications for policymakers and stakeholders seeking to improve ANC coverage. Removing the tuition barrier at the secondary level has shown to be a powerful strategy for advancing health outcomes and educational attainment. As governments across Africa consider eliminating tuition fees at the secondary level, this study provides valuable evidence about the impacts on reproductive health outcomes. While investing in free education requires initial investment, the long-term benefits for both human development and economic growth far outweigh the costs.

PurposeTo determine whether a diagnosis of a perinatal mood and anxiety disorder (PMAD) is associated with adverse perinatal outcomes.MethodsMental health symptom screening and diagnostic data from 82 women with single gestation in the Healthy Babies Before Birth study conducted from 2013 to 2018 were obtained by clinic interview. If a woman scored over 10 on the Patient Health Questionnaire (PHQ-9) or endorsed the suicidality item; or scored over 7 on the Overall Anxiety Severity and Impairment Scale (OASIS), a Structured Clinical Interview for DSM-IV (SCID) Axis I Disorders was administered. An adverse perinatal outcome was operationalized as a diagnosis of gestational diabetes mellitus, intrauterine growth restriction, preeclampsia, chorioamnionitis, hemorrhage, fetal death, preterm birth, or a low birthweight baby, and abstracted from the medical records.ResultsWomen were between 22.0 and 45.0 years old (Mean age = 33.1 ± 4.3). Mean BMI was 24.7 ± 5.6 (Range 16.8 to 47.1). Nineteen percent (16) of the 82 women had a SCID diagnosis of a PMAD. Thirty-seven percent (30) had a diagnosed adverse perinatal outcome. Multiple logistic regression was conducted with these predictors: SCID diagnosis of a PMAD, maternal age, BMI. All predictors were significant with respective odds ratios as follows: OR = 3.58, 95% CI 1.03-12.44, p = .045; OR = 2.30, 95% CI 1.21-4.38, p = .011; OR = 1.69, 95% CI 1.06-2.69, p = .027.ConclusionsA PMAD diagnosis was associated with 3.5 times higher odds of having an adverse perinatal outcome. For every 5 years a woman aged or every five units her BMI increased her odds of having an adverse perinatal outcome increased. Older age and increased BMI are well established adverse perinatal outcome risk factors. These results suggest that mental illness risk should also be consistently assessed in obstetric settings.

BACKGROUND: Pertussis is a contagious respiratory disease. Maternal tetanus-diphtheria-acellular pertussis vaccination during pregnancy has been recommended by the United States Centres for Disease Control (US CDC) Advisory Committee on Immunization Practices (ACIP) for unvaccinated pregnant women since October 2011 to prevent infection among infants; in 2012, ACIP extended this recommendation to every pregnancy, regardless of previous vaccination status. The population-level effect of these recommendations on infant pertussis is unknown. This study aimed to examine the impact of the 2011/2012 ACIP pertussis recommendation on pertussis incidence and mortality among US infants. METHODS: We used monthly data on pertussis deaths among infants aged

OBJECTIVE: To describe changes over time in resuscitation, survival, and morbidity of extremely preterm infants in California. STUDY DESIGN: This population-based, retrospective cohort study includes infants born ≤28 weeks. Linked birth certificates and hospital discharge records were used to evaluate active resuscitation, survival, and morbidity across two epochs (2011-2014, 2015-2019). RESULTS: Of liveborn infants, 0.6% were born ≤28 weeks. Active resuscitation increased from 16.9% of 22-week infants to 98.1% of 25-week infants and increased over time in 22-, 23-, and 25-week infants (p-value ≤ 0.01). Among resuscitated infants, survival to discharge increased from 33.2% at 22 weeks to 96.1% at 28 weeks. Survival without major morbidity improved over time for 28-week infants (p-value

BackgroundSynthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1-2 spot samples during pregnancy and limited diversity of populations.ObjectiveTo study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program.ResultsWhile many associations were modest and statistically imprecise, a 1-unit increase in log10 pregnancy averaged concentration of benzophenone-3 and methylparaben were associated with decreases in birthweight, birthweight adjusted for gestational age and SGA. Increases in the odds of being SGA were 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%), respectively. Bisphenol S in third trimester was also associated with SGA (OR 1.52, 95% CI 1.08, 2.13). Associations of benzophenone-3 and methylparaben with PTB and LBW were null. In addition, a 1-unit increase in log10 pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: -67%, -2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: -53%, 8%).DiscussionIn a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life.

Respiratory distress (RD) has been reported in SARS-CoV-2 exposed uninfected (SEU) term neonates. Prior studies suggest that prenatal exposure to Coronavirus Disease 19 (COVID-19) may activate an inflammatory cascade in the newborn airway. In this study, we examine the relationship between maternal COVID-19 vaccination and neonatal RD using a longitudinal cohort of mother-infant pairs in Los Angeles, CA. Two-hundred and twenty-one mothers with laboratory confirmed SARS-CoV-2 during pregnancy and 227 exposed fetuses are enrolled in our study. Maternal disease severity and neonatal RD variables were defined based on current accepted clinical criteria. To explore the multifactorial associations between maternal COVID-19 parameters and infant RD, we utilize a multivariable logistic regression model and a proteomic sub-analysis to propose a pathway for the development of RD following in utero exposure to SARS-CoV-2. Unusually high rates of RD are observed in SEU infants (17%). The odds ratio of RD is 3.06 (95% CI:1.08-10.21) in term neonates born to unvaccinated individuals versus those born to individuals vaccinated prior to maternal infection. Proteomic analysis reveals a robust inflammatory response associated with ciliary dysregulation and enhanced IgE production among SEU neonates with RD. Maternal vaccination against COVID-19 reduces the frequency of neonatal RD.

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB;

BackgroundHypoxic-ischemic brain injury/encephalopathy affects about 1.15 million neonates per year, 96% of whom are born in low- and middle-income countries. Therapeutic hypothermia is not effective in this setting, possibly because injury occurs significantly before birth. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal azithromycin administration in near-term lambs following global ischemic injury to support earlier treatment approaches.MethodsEwes and their lambs of both sexes (n=34, 141-143 days) were randomly assigned to receive azithromycin or placebo before delivery as well as postnatally. Lambs were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Outcomes were assessed over a 6-day period.ResultsWhile maternal azithromycin exhibited relatively low placental transfer, azithromycin-treated lambs recovered spontaneous circulation faster following the initiation of cardiopulmonary resuscitation and were extubated sooner. Additionally, peri- and postnatal azithromycin administration was well tolerated, demonstrating a 77-hour plasma elimination half-life, as well as significant accumulation in the brain and other tissues. Azithromycin administration resulted in a systemic immunomodulatory effect, demonstrated by reductions in proinflammatory IL-6 (interleukin-6) levels. Treated lambs exhibited a trend toward improved neurodevelopmental outcomes while histological analysis revealed that azithromycin supported white matter preservation and attenuated inflammation in the cingulate and parasagittal cortex.ConclusionsPerinatal azithromycin administration enhances neonatal resuscitation, attenuates neuroinflammation, and supports limited improvement of select histological outcomes in an ovine model of hypoxic-ischemic brain injury/encephalopathy.

Meta-analyses consistently have found that antenatal multiple micronutrient supplementation (MMS) compared with iron and folic acid (IFA) alone reduce adverse birth outcomes. In 2020, the World Health Organization (WHO) placed a conditional recommendation for MMS and requested additional trials using ultrasounds to establish gestational age, because the evidence on low birthweight (LBW), preterm birth and small for gestational age (SGA) was considered inconsistent. We conducted meta-analyses to determine if the effects of MMS on LBW, preterm birth and SGA differed by gestational age assessment method. Using data from the 16 trials in the WHO analyses, we calculated the effect estimates of MMS versus IFA on birth outcomes (generic inverse variance method and random effects model) stratified by method of gestational age assessment: ultrasound, prospective collection of the date of last menstrual period (LMP) and confirmation of pregnancy by urine test and recall of LMP. The effects of MMS versus IFA on birthweight, preterm birth and SGA appeared consistent across subgroups with no evidence of subgroup differences (p > 0.05). When limited to the seven trials that used ultrasound, the beneficial effects of MMS were demonstrated: risk ratios of 0.87 (95% confidence interval [CI] 0.78-0.97) for LBW, 0.90 (95% CI, 0.79-1.03) for preterm birth and 0.9 (95% CI, 0.83-0.99) for SGA. Sensitivity analyses indicated consistency in the results. These results, together with recent analyses demonstrating comparable effects of MMS (vs. IFA) on maternal anaemia outcomes, strengthen the evidence to support a transition from IFA to MMS programmes in low- and middle-income countries.

BackgroundStructural racism contributes to racial disparities in adverse perinatal outcomes. We sought to determine if structural racism is associated with adverse outcomes among Black preterm infants postnatally.MethodsObservational cohort study of 13,321 Black birthing people who delivered preterm (gestational age 22-36 weeks) in California in 2011-2017 using a statewide birth cohort database and the American Community Survey. Racial and income segregation was quantified by the Index of Concentration at the Extremes (ICE) scores. Multivariable generalized estimating equations regression models were fit to test the association between ICE scores and adverse postnatal outcomes: frequent acute care visits, readmissions, and pre- and post-discharge death, adjusting for infant and birthing person characteristics and social factors.ResultsBlack birthing people who delivered preterm in the least privileged ICE tertiles were more likely to have infants who experienced frequent acute care visits (crude risk ratio [cRR] 1.3 95% CI 1.2-1.4), readmissions (cRR 1.1 95% CI 1.0-1.2), and post-discharge death (cRR 1.9 95% CI 1.2-3.1) in their first year compared to those in the privileged tertile. Results did not differ significantly after adjusting for infant or birthing person characteristics.ConclusionStructural racism contributes to adverse outcomes for Black preterm infants after hospital discharge.Impact statementStructural racism, measured by racial and income segregation, was associated with adverse postnatal outcomes among Black preterm infants including frequent acute care visits, rehospitalizations, and death after hospital discharge. This study extends our understanding of the impact of structural racism on the health of Black preterm infants beyond the perinatal period and provides reinforcement to the concept of structural racism contributing to racial disparities in poor postnatal outcomes for preterm infants. Identifying structural racism as a primary cause of racial disparities in the postnatal period is necessary to prioritize and implement appropriate structural interventions to improve outcomes.

The coronavirus disease 2019 (COVID-19) pandemic increased food insecurity among US households, however, little is known about how infants, who rely primarily on human milk and/or infant formula, were impacted. We conducted an online survey with US caregivers of infants under 2 years of age (N = 319) to assess how the COVID-19 pandemic impacted breastfeeding, formula-feeding and household ability to obtain infant-feeding supplies and lactation support (68% mothers; 66% White; 8% living in poverty). We found that 31% of families who used infant formula indicated that they experienced various challenges in obtaining infant formula, citing the following top three reasons: the formula was sold out (20%), they had to travel to multiple stores (21%) or formula was too expensive (8%). In response, 33% of families who used formula reported resorting to deleterious formula-feeding practices such as diluting formula with extra water (11%) or cereal (10%), preparing smaller bottles (8%) or saving leftover mixed bottles for later (11%). Of the families who fed infants human milk, 53% reported feeding changes directly as a result of the pandemic, for example, 46% increased their provisioning of human milk due to perceived benefits for the infant's immune system (37%), ability to work remotely/stay home (31%), concerns about money (9%) or formula shortages (8%). Fifteen percent of families who fed human milk reported that they did not receive the lactation support they needed and 4.8% stopped breastfeeding. To protect infant food and nutrition security, our results underscore the need for policies to support breastfeeding and ensure equitable and reliable access to infant formula.

Exposure to traumatic events during pregnancy may influence pregnancy and birth outcomes. Growing evidence suggests that exposure to traumatic events well before pregnancy, such as childhood maltreatment (CM), also may influence the course of pregnancy and risk of adverse birth outcomes. We aimed to estimate associations between maternal CM exposure and small-for-gestational-age birth (SGA) and preterm birth (PTB) in a diverse US sample, and to examine whether common CM-associated health and behavioral sequelae either moderate or mediate these associations. The Measurement of Maternal Stress (MOMS) Study was a prospective cohort study that enrolled 744 healthy English-speaking participants ≥ 18 years with a singleton pregnancy, who were

AimTo assess the inter-assessor reliability of the Motor Optimality Score-Revised (MOS-R) when used in infants at elevated likelihood for adverse neurological outcome.MethodsMOS-R were assessed in three groups of infants by two assessors/cohort. Infants were recruited from longitudinal projects in Sweden (infants born extremely preterm), India (infants born in low-resource communities) and the USA (infants prenatally exposed to SARS-CoV-2). Intraclass correlation coefficients (ICC) and kappa (κw) were applied. ICC of MOS-R subcategories and total scores were presented for cohorts together and separately and for age-spans: 9-12, 13-16 and 17-25-weeks post-term age.Results252 infants were included (born extremely preterm n = 97, born in low-resource communities n = 97, prenatally SARS-CoV-2 exposed n = 58). Reliability of the total MOS-R was almost perfect (ICC: 0.98-0.99) for all cohorts, together and separately. Similar result was found for age-spans (ICC: 0.98-0.99). Substantial to perfect reliability was shown for the MOS-R subcategories (κw: 0.67-1.00), with postural patterns showing the lowest value 0.67.ConclusionThe MOS-R can be used in high-risk populations with substantial to perfect reliability, both in regards of total/subcategory scores as well as in different age groups. However, the subcategory postural patterns as well as the clinical applicability of the MOS-R needs further study.

BackgroundPreterm birth (PTB) is a global health epidemic, sub-Saharan Africa is severely impacted due to its limited healthcare resources. Pregnancy knowledge, cultural beliefs and practices play a role in the identification of risk and management of PTB. This study explored knowledge, understandings, cultural beliefs and attitudes to pregnancy and PTB, as well as cultural considerations for the introduction of an intravaginal device which could be used to identify PTB risk.MethodsQualitative research was conducted in South Africa and Kenya. In-depth interviews were conducted using semi-structured guides with women with a history of PTB (n = 10), healthcare providers (n = 16) and health systems experts (n = 10); and 26 focus group discussions with pregnant women seeking antenatal care (n = 132) and community male partners/fathers (n = 54). Interviews/discussions were transcribed, translated, and analysed thematically.ResultsPregnancy knowledge, especially for first time pregnancies was poor, with many reporting late entry to antenatal care. Knowledge about PTB was understood in terms of gestational age, weight or small size of baby, with concerns about long term health and stigma. Various risk factors for PTB were described, including those related to traditions and beliefs of witchcraft/curses. Cultural practices, such as the use of traditional medicines and pica, and religion and its impact on health seeking behaviour were also viewed as risk factors. Although insertion of intravaginal devices was not widely acceptable in traditional communities, especially during pregnancy, it was felt that the use of one to detect risk of PTB would be accepted if proven effective in reducing PTB risk.ConclusionsVarious culturally-informed beliefs exist which explain understandings of and attitudes toward pregnancy, pregnancy risk, and PTB. An inclusive exploratory process is critical to facilitate an understanding of the beliefs and traditions which could impact the introduction and design of a product to detect the risk of PTB.

BackgroundThe California Preterm Birth Initiative is a community-engaged research effort focused on addressing racial disparities in birth outcomes.ObjectivesTo highlight three community-academic partnership strategies and identify partners' lessons learned and recommendations.MethodsWe conducted interviews (n = 38), four focus groups (n = 23), a document review (n = 174), and meeting/event observations (n = 36). We performed content analysis and structural and emerging coding of the data, which involved extracting and sorting information into themes.Lessons learnedFive themes emerged across the strategies as essential for successful partnerships addressing racial disparities: 1) incorporate a racial equity approach; 2) value community knowledge; 3) ensure accountability to community priorities; 4) build relationships and trust; and 5) address structural barriers to community-academic partnerships.ConclusionsCommunity-academic partnerships addressing racial health disparities should confront internal and structural power dynamics early on and support affected communities to lead the efforts, including committing to funding and capacity-building activities to ensure research justice.

BackgroundSocial support is associated with decreased symptoms of postpartum mood and anxiety disorders (PMAD) in mothers of healthy infants, but less is known about social support and PMADs in mothers with preterm infants. The purpose of this study was to examine the relationship between social support and symptoms of PMADs reported by mothers in the months following hospital discharge of their preterm infant.MethodsMothers of infants less than 33 weeks gestational age were enrolled from neonatal intensive care units (NICU) at 6 sites. Mothers completed PMAD measures of depression, anxiety and post-traumatic stress approximately 3 months following their infant's discharge. Multivariable regression was used to evaluate relationships between social support and PMAD measures.ResultsOf 129 mothers, 1 in 5 reported clinically significant PMAD symptoms of: depression (24%), anxiety (19%), and post-traumatic stress (20%). Social support was strongly inversely associated with all 3 PMADs. Social support explained between 21% and 26% of the variance in depression, anxiety and post-traumatic stress symptoms.ConclusionIncreased social support may buffer PMAD symptoms in mothers of preterm infants after discharge. Research is needed to determine effective screening and interventions aimed at promoting social support for all parents during and following their infant's hospitalisation.

Observational studies have linked early-life antibiotic exposure to increased risk of obesity in children in high income settings. We evaluated whether neonatal antibiotic exposure led to changes in infant growth at 6 months of age in Burkina Faso. Neonates aged 8 to 27 days of age who weighed at least 2,500 g at the time of enrollment were randomized in a 1:1 fashion to a single oral 20-mg/kg dose of azithromycin or equivalent volume of placebo from April 2019 through December 2020. Weight, length, and mid-upper-arm circumference (MUAC) were measured at baseline and 6 months of age. Growth outcomes, including weight gain in grams per day, length change in millimeters per day, and changes in weight-for-age Z-score (WAZ), weight-for-length Z-score (WLZ), length-for-age Z-score (LAZ), and MUAC were compared among neonates randomized to azithromycin compared with placebo. Among 21,832 neonates enrolled in the trial, median age at enrollment was 11 days, and 50% were female. We found no evidence of a difference in weight gain (mean difference -0.009 g/day, 95% confidence interval [CI]: -0.16 to 0.14, P = 0.90), length change (mean difference 0.003 mm/day, 95% CI: -0.002 to 0.007, P = 0.23), or WAZ (mean difference -0.005 SD, 95% CI: -0.03 to 0.02, P = 0.72), WLZ (mean difference -0.01 SD, 95% CI: -0.05 to 0.02, P = 0.39), LAZ (mean difference 0.01, 95% CI: -0.02 to 0.04, P = 0.47), or MUAC (mean difference 0.01 cm, 95% CI: -0.02 to 0.04, P = 0.49). These results do not suggest that azithromycin has growth-promoting properties in infants when administered during the neonatal period. Trial registration: ClinicalTrials.gov NCT03682653.

BackgroundPreterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States.ObjectiveWe leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin.Study designThis study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models.ResultsApproximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis.ConclusionHere, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation.

BACKGROUND AND OBJECTIVES: Although mortality rates are highest for infants of teens aged 15 to 19, no studies have examined the long-term trends by race and ethnicity, urbanicity, or maternal age. The objectives of this study were to examine trends and differences in mortality for infants of teens by race and ethnicity and urbanicity from 1996 to 2019 and estimate the contribution of changes in the maternal age distribution and maternal age-specific (infant) mortality rates (ASMRs) to differences in infant deaths in 1996 and 2019. METHODS: We used 1996 to 2019 period-linked birth and infant death data from the United States to assess biennial mortality rates per 1000 live births. Pairwise comparisons of rates were conducted using z test statistics and Joinpoint Regression was used to examine trends. Kitagawa decomposition analysis was used to estimate the proportion of change in infant deaths because of changes in the maternal age distribution and ASMRs. RESULTS: From 1996 to 2019, the mortality rate for infants of teens declined 16.7%, from 10.30 deaths per 1000 live births to 8.58. The decline was significant across racial and ethnic and urbanization subgroups; however, within rural counties, mortality rates did not change significantly for infants of Black or Hispanic teens. Changes in ASMRs accounted for 93.3% of the difference between 1996 and 2019 infant mortality rates, whereas changes in the maternal age distribution accounted for 6.7%. CONCLUSIONS: Additional research into the contextual factors in rural counties that are driving the lack of progress for infants of Black and Hispanic teens may help inform efforts to advance health equity.

Human milk is universally recognized as the preferred food for infants during the first 6 mo of life because it provides not only essential and conditionally essential nutrients in necessary amounts but also other biologically active components that are instrumental in protecting, communicating important information to support, and promoting optimal development and growth in infants. Despite decades of research, however, the multifaceted impacts of human milk consumption on infant health are far from understood on a biological or physiological basis. Reasons for this lack of comprehensive knowledge of human milk functions are numerous, including the fact that milk components tend to be studied in isolation, although there is reason to believe that they interact. In addition, milk composition can vary greatly within an individual as well as within and among populations. The objective of this working group within the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to provide an overview of human milk composition, factors impacting its variation, and how its components may function to coordinately nourish, protect, and communicate complex information to the recipient infant. Moreover, we discuss the ways whereby milk components might interact such that the benefits of an intact milk matrix are greater than the sum of its parts. We then apply several examples to illustrate how milk is better thought of as a biological system rather than a more simplistic "mixture" of independent components to synergistically support optimal infant health.

The goal of Working Group 1 in the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project was to outline factors influencing biological processes governing human milk secretion and to evaluate our current knowledge of these processes. Many factors regulate mammary gland development in utero, during puberty, in pregnancy, through secretory activation, and at weaning. These factors include breast anatomy, breast vasculature, diet, and the lactating parent's hormonal milieu including estrogen, progesterone, placental lactogen, cortisol, prolactin, and growth hormone. We examine the effects of time of day and postpartum interval on milk secretion, along with the role and mechanisms of lactating parent-infant interactions on milk secretion and bonding, with particular attention to the actions of oxytocin on the mammary gland and the pleasure systems in the brain. We then consider the potential effects of clinical conditions including infection, pre-eclampsia, preterm birth, cardiovascular health, inflammatory states, mastitis, and particularly, gestational diabetes and obesity. Although we know a great deal about the transporter systems by which zinc and calcium pass from the blood stream into milk, the interactions and cellular localization of transporters that carry substrates such as glucose, amino acids, copper, and the many other trace metals present in human milk across plasma and intracellular membranes require more research. We pose the question of how cultured mammary alveolar cells and animal models can help answer lingering questions about the mechanisms and regulation of human milk secretion. We raise questions about the role of the lactating parent and the infant microbiome and the immune system during breast development, secretion of immune molecules into milk, and protection of the breast from pathogens. Finally, we consider the effect of medications, recreational and illicit drugs, pesticides, and endocrine-disrupting chemicals on milk secretion and composition, emphasizing that this area needs much more research attention.

ProblemIn the United States, Black women are disproportionately impacted by inequities in maternal health.BackgroundCommunity doula support may improve birth outcomes and experiences, including lower rates of preterm birth and low birthweight and increases in positive birthing experiences. Few studies have explored client experiences with doula care, specifically community doula care.AimTo explore Black doula clients' motivations for seeking and experiences with community doula care.MethodsData are from a mixed methods process evaluation of an organization providing free community doula services in San Francisco, California. We conducted two rounds of qualitative interviews with doula clients who identified as Black or Pacific Islander between August 2019 and March 2020. Interviews explored clients' knowledge of, experiences with, and motivations for seeking doula care and their perceptions of the services they received. We utilized a Rapid Assessment Process to synthesize findings and thematic analysis.FindingsClients' motivations for seeking doula care included general lack of support and knowledge of mistreatment experienced by Black women in hospital settings. Doulas provided support in the form of information about the perinatal period and clients' rights, advocacy in hospital settings, and connection to resources beyond pregnancy and birth. Some clients described doulas as helping them stay focused and make decisions during difficult labor experiences and described positive birth experiences despite experiencing complications.ConclusionCommunity doulas play an instrumental role in the birth experiences of Black women and birthing people. Efforts should be made to expand access to this needed support via policy and hospital practices.

BackgroundMaternal age is increasingly recognized as a predictor of birth outcomes. Given the importance of birth and growth outcomes for children's development, wellbeing and survival, this study examined the effect of maternal age on infant birth and growth outcomes at 6 months and mortality. Additionally, we conducted quantitative bias analysis (QBA) to estimate the role of selection bias and unmeasured confounding on the effect of maternal age on infant mortality.MethodsWe used data from randomized-controlled trials (RCTs) of 21 555 neonates in Burkina Faso conducted in 2019-2020. Newborns of mothers aged 13-19 years (adolescents) and 20-40 years (adults) were enrolled in the study 8-27 days after birth and followed for 6 months. Measurements of child's anthropometric measures were collected at baseline and 6 months. We used multivariable linear regression to compare child anthropometric measures at birth and 6 months, and logistic regression models to obtain the odds ratio (OR) of all-cause mortality. Using multidimensional deterministic analysis, we assessed scenarios in which the difference in selection probability of adolescent and adult mothers with infant mortality at 6 months increased from 0% to 5%, 10%, 15% and 20% if babies born to adolescent mothers more often died during the first week or were of lower weight and hence were not eligible to be included in the original RCT. Using probabilistic bias analysis, we assessed the role of unmeasured confounding by socio-economic status (SES).ResultsBabies born to adolescent mothers on average had lower weight at birth, lower anthropometric measures at baseline, similar growth outcomes from enrolment to 6 months and higher odds of all-cause mortality by 6 months (adjusted OR = 2.17, 95% CI 1.35 to 3.47) compared with those born to adult mothers. In QBA, we found that differential selection of adolescent and adult mothers could bias the observed effect (OR = 2.24, 95% CI 1.41 to 3.57) towards the null [bias-corrected OR range: 2.37 (95% CI 1.49 to 3.77) to 2.84 (95% CI 1.79 to 4.52)], whereas unmeasured confounding by SES could bias the observed effect away from the null (bias-corrected OR: 2.06, 95% CI 1.31 to 2.64).ConclusionsOur findings suggest that delaying the first birth from adolescence to adulthood may improve birth outcomes and reduce mortality of neonates. Babies born to younger mothers, who are smaller at birth, may experience catch-up growth, reducing some of the anthropometric disparities by 6 months of age.

This article aimed to evaluate whether a substance-related diagnosis (SRD; i.e., alcohol, opioids, cannabis, stimulants, nicotine) predicts the likelihood and co-occurrence of preterm (20-37 weeks' gestation) and cesarean delivery.This study reviewed electronic health record data on women (aged 18-44 years) who delivered a single live or stillbirth at ≥ 20 weeks of gestation from 2012 to 2019. Women with and without an SRD were matched on key demographic characteristics at a 1:1 ratio. Adjusting for covariates, odds ratios and 95% confidence intervals were calculated.Of the 19,346 deliveries, a matched cohort of 2,158 deliveries was identified. Of these, 1,079 (50%) had an SRD, 280 (13%) had a preterm delivery, 833 (39%) had a cesarean delivery, and 166 (8%) had a co-occurring preterm and cesarean delivery. An SRD was significantly associated with preterm and cesarean delivery (AOR = 1.84 [95% CI, 1.41-2.39], p-value=

Preterm birth remains the leading cause of morbidity and mortality among nonanomalous neonates in the United States. Unfortunately, preterm birth rates remain high despite current medical interventions such as progestogen supplementation and cerclage placement. Case management, which encompasses coordinated care aimed at providing a more comprehensive and supportive environment, is a key component in improving health and reducing costs in other areas of medicine. However, it has not made its way into the general lexicon and practice of obstetrical care. Case management intended for decreasing prematurity or ameliorating its consequences may include specialty clinics, social services, coordination of specialty services such as nutrition counseling, home visits or frequent phone calls by specially trained personnel, and other elements described herein. It is not currently included in nor is it advocated for as a recommended prematurity prevention approach in the American College of Obstetricians and Gynecologists or Society for Maternal-Fetal Medicine guidelines for medically indicated or spontaneous preterm birth prevention. Our review of existing evidence finds consistent reductions or trends toward reductions in preterm birth with case management, particularly among individuals with high a priori risk of preterm birth across systematic reviews, metaanalyses, and randomized controlled studies. These findings suggest that case management has substantial potential to improve the environmental, behavioral, social, and psychological factors with patients at risk of preterm birth.

ObjectiveDevelop and validate a resiliency score to predict survival and survival without neonatal morbidity in preterm neonates

ImportanceClimate change is affecting the earth, resulting in more extreme temperatures and weather, rising sea levels, more frequent natural disasters, and displacement of populations of plants and animals, including people and insects. These changes affect food and housing security, vector-borne illnesses, and access to clean air and water, all of which influence human health.Evidence and resultsThere are a number of adverse health outcomes linked to heat, air pollution from wildfires, stress from natural disasters, and other elements of climate change. Pregnant people are especially vulnerable to the health harms resulting from climate change, namely, preterm birth, small for gestational age, hypertensive disorders of pregnancy, and other adverse reproductive health and birth outcomes. Strategies to minimize these harms include mitigation and adaptation.Conclusions and relevancePhysicians are in a unique position to protect the health of pregnant persons and children by advocating for policy changes that address climate change and providing clinical recommendations for patients to protect themselves from the health impacts of climate hazards.

Background: Preconception diabetes is strongly associated with adverse birth outcomes. Less is known about the effects of elevated glycemia at levels below clinical cutoffs for diabetes. In this study, we estimated associations between preconception diabetes, prediabetes, and hemoglobin A1c (HbA1c) on the risk of preterm birth, and evaluated whether associations were modified by access to or utilization of health care services. Materials and Methods: We used data from Add Health, a US prospective cohort study with five study waves to date. At Wave IV (ages 24-32), glucose and HbA1c were measured. At Wave V (ages 32-42), women with a live birth reported whether the baby was born preterm. The analytic sample size was 1989. Results: The prevalence of preterm birth was 13%. Before pregnancy, 6.9% of women had diabetes, 23.7% had prediabetes, and 69.4% were normoglycemic. Compared to the normoglycemic group, women with diabetes had 2.1 (confidence interval [95% CI]: 1.5-2.9) times the risk of preterm birth, while women with prediabetes had 1.3 (95% CI: 1.0, 1.7) times the risk of preterm birth. There was a nonlinear relationship between HbA1c and preterm birth such that risk of preterm birth emerged after HbA1c = 5.7%, a standard cutoff for prediabetes. The excess risks of preterm birth associated with elevated HbA1c were four to five times larger among women who reported unstable health care coverage and among women who used the emergency room as usual source of care. Conclusion: Our findings replicate prior research showing strong associations between preconception diabetes and preterm birth, adding that prediabetes is also associated with higher risk. Policies and interventions to enhance access and utilization of health care among women before pregnancy should be examined.

Prenatal tobacco use among Alaska Native (AN) women has decreased substantially over the past two decades. Previous research suggests that providing AN women with feedback regarding fetal exposure to tobacco may further promote cessation. Transporters in the placenta regulate fetal exposure to nutrients and xenobiotics, including compounds associated with tobacco use. We examined whether prenatal tobacco use impacts transporter expression in the placenta, and whether this is influenced by fetal sex, degree of tobacco exposure, or transporter genotype. At delivery, we obtained placental samples from AN research participants who smoked cigarettes, used commercial chew or iqmik (oral tobacco), or did not use tobacco during pregnancy. Transporter expression was evaluated using qRT-PCR and Western blotting and tested for correlations between transcript levels and urinary biomarkers of tobacco use. The impact of BCRP/ABCG2 and OATP2B1/SLCO2B1 genotypes on protein expression was also examined. Oral tobacco use was associated with decreased P-gp and increased MRP1, MRP3, LAT1, and PMAT mRNA expression. Transcript levels of multiple transporters significantly correlated with tobacco biomarkers in maternal and fetal urine. In women carrying male fetuses, both smoking and oral tobacco were associated with decreased P-gp. Oral tobacco was also associated with decreased LAT1 in women carrying female fetuses. BCRP and OATP2B1 genotypes did not appear to impact protein expression. In conclusion, prenatal tobacco use is associated with altered expression of multiple placental transporters which differs by fetal sex. As transcript levels of multiple transporters were significantly correlated with tobacco use biomarkers, eliminating prenatal tobacco use should alleviate these changes.

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has impacted all patient populations including pregnant mothers. There is an incomplete understanding of SARS-CoV-2 pathogenesis and transmission potential at this time and the resultant anxiety has led to variable breastfeeding recommendations for suspected or confirmed mothers with novel coronavirus disease 2019 (COVID-19). Due to the potential concern for transmission of infection from maternal respiratory secretions to the newborn, temporary separation of the maternal-baby dyad, allowing for expressed breast milk to be fed to the infant, was initially recommended but later revised to include breastfeeding by the American Academy of Pediatrics in contrast to international societies, which recommend direct breastfeeding. This separation can have negative health and emotional implications for both mother and baby. Only two publications have reported SARS-CoV-2 in human breast milk but the role of breast milk as a vehicle of transmission of COVID-19 to the newborns still remains unclear and may indeed be providing protective antibodies against SARS-CoV-2 infection even in infected neonates. Other modes of transmission of infection to neonates from infected mothers or any care providers cannot be overemphasized. Symptomatic mothers on hydroxychloroquine can safely breastfeed and no adverse effects were reported in a baby treated with remdesivir in another drug trial. The excretion of sarilumab in human breast milk is unknown at this time. Hence, given the overall safety of breast milk and both short-term and long-term nutritional, immunological, and developmental advantages of breast milk to newborn, breast milk should not be withheld from baby. The setting of maternal care, severity of maternal infection and availability of resources can impact the decision of breastfeeding, the role of shared decision making on breastfeeding between mother and physician needs to be emphasized. We strongly recommend direct breastfeeding with appropriate hygiene precautions unless the maternal or neonatal health condition warrants separation of this dyad. KEY POINTS: · Breastmilk does not appear to play a significant role in transmission of SARS-CoV-2.. · Mother-baby separation has negative health and emotional consequences.. · Mothers with suspected or confirmed COVID-19 can directly breastfeed with appropriate precautions..

Neurodevelopmental impairments are the most common extracardiac morbidities among patients with complex congenital heart disease (CHD) across the lifespan. Robust clinical research in this area has revealed several cardiac, medical, and social factors that can contribute to neurodevelopmental outcome in the context of CHD. Studies using brain magnetic resonance imaging (MRI) have been instrumental in identifying quantitative and qualitative difference in brain structure and maturation in this patient population. Full-term newborns with complex CHD are known to have abnormal microstructural and metabolic brain development with patterns similar to those seen in premature infants at approximately 34 to 36 weeks' gestation. With the advent of fetal brain MRI, these brain abnormalities are now documented as they begin in utero, as early as the third trimester. Importantly, disturbed brain development in utero is now known to be independently associated with neurodevelopmental outcome in early childhood, making the prenatal period an important timeframe for potential interventions. Advances in fetal brain MRI provide a robust imaging tool to use in future neuroprotective clinical trials. The causes of abnormal fetal brain development are multifactorial and include cardiovascular physiology, genetic abnormalities, placental impairment, and other environmental and social factors. This review provides an overview of current knowledge of brain development in the context of CHD, common prenatal imaging tools to evaluate the developing fetal brain in CHD, and known risk factors contributing to brain immaturity.

The risk of vertical transmission from breastfeeding with HIV (BFHIV) has been found to be very low in optimal scenarios with sustained maternal viral suppression during pregnancy and postpartum. Medical providers must account for the risk of this serious adverse event alongside parental autonomy, breastfeeding benefits, and patient values. To assess provider practices, comfort, and challenges with BFHIV, an online mixed-method survey was sent to breastfeeding and HIV provider listservs from June to July 2021. The target population was US medical professionals from diverse practice settings with experience in clinical issues associated with BFHIV, including physicians, advanced practice providers, nurses, and lactation consultants. Data analysis utilized nonparametric hypothesis testing, ordinal regression, and reflexive thematic analysis. Most providers reported counseling pregnant people with HIV on infant feeding choices, but fewer specifically endorsed counseling about breastfeeding. Of 84 unique institutions identified by 100 included respondents, 10% had an institutional protocol supporting BFHIV. Institutional protocols were associated with higher degrees of provider comfort with BFHIV in optimal scenario clinical vignettes. Providers perceived that White patients faced fewer BFHIV barriers than patients with other racial identities. Discomfort balancing the goals to protect infants from infection risk and support the parent's role in infant feeding decisions was a key theme in free text responses; this manifested in a spectrum of management styles ranging from patient's informed choice to paternalism. This study highlights the tension providers navigate regarding BFHIV discussions, calling for patient care guidelines and protocols grounded in risk reduction and respect of patient autonomy.

ImportanceUnderstanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood.ObjectiveTo determine the association of genetic diseases with infant mortality.Design, setting, and participantsThis cohort study was conducted at a large pediatric hospital system in San Diego County (California) and included 546 infants (112 infant deaths [20.5%] and 434 infants [79.5%] with acute illness who survived; age, 0 to 1 year) who underwent diagnostic whole-genome sequencing (WGS) between January 2015 and December 2020. Data analysis was conducted between 2015 and 2022.ExposureInfants underwent WGS either premortem or postmortem with semiautomated phenotyping and diagnostic interpretation.Main outcomes and measuresProportion of infant deaths associated with single-locus genetic diseases.ResultsAmong 112 infant deaths (54 girls [48.2%]; 8 [7.1%] African American or Black, 1 [0.9%] American Indian or Alaska Native, 8 [7.1%] Asian, 48 [42.9%] Hispanic, 1 [0.9%] Native Hawaiian or Pacific Islander, and 34 [30.4%] White infants) in San Diego County between 2015 and 2020, single-locus genetic diseases were the most common identifiable cause of infant mortality, with 47 genetic diseases identified in 46 infants (41%). Thirty-nine (83%) of these diseases had been previously reported to be associated with childhood mortality. Twenty-eight death certificates (62%) for 45 of the 46 infants did not mention a genetic etiology. Treatments that can improve outcomes were available for 14 (30%) of the genetic diseases. In 5 of 7 infants in whom genetic diseases were identified postmortem, death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission.Conclusions and relevanceIn this cohort study of 112 infant deaths, the association of genetic diseases with infant mortality was higher than previously recognized. Strategies to increase neonatal diagnosis of genetic diseases and immediately implement treatment may decrease infant mortality. Additional study is required to explore the generalizability of these findings and measure reduction in infant mortality.

Pregnancy-related acute respiratory distress syndrome (ARDS) is fast becoming a growing and clinically relevant subgroup of ARDS amidst global outbreaks of various viral respiratory pathogens that include H1N1-influenza, severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS), and the most recent COVID-19 pandemic. Pregnancy is a risk factor for severe viral-induced ARDS and commonly associated with poor maternal and fetal outcomes including fetal growth-restriction, preterm birth, and spontaneous abortion. Physiologic changes of pregnancy further compounded by mechanical and immunologic alterations are theorized to impact the development of ARDS from viral pneumonia. The COVID-19 sub-phenotype of ARDS share overlapping molecular features of maternal pathogenicity of pregnancy with respect to immune-dysregulation and endothelial/microvascular injury (i.e., preeclampsia) that may in part explain a trend toward poor maternal and fetal outcomes seen with severe COVID-19 maternal infections. To date, current ARDS diagnostic criteria and treatment management fail to include and consider physiologic adaptations that are unique to maternal physiology of pregnancy and consideration of maternal-fetal interactions. Treatment focused on lung-protective ventilation strategies have been shown to improve clinical outcomes in adults with ARDS but may have adverse maternal-fetal interactions when applied in pregnancy-related ARDS. No specific pharmacotherapy has been identified to improve outcomes in pregnancy with ARDS. Adjunctive therapies aimed at immune-modulation and anti-viral treatment with COVID-19 infection during pregnancy have been reported but data in regard to its efficacy and safety is currently lacking.

BackgroundThe United States (US) data suggest fewer-than-expected preterm births in 2020, but no study has examined the impact of exposure to the early COVID-19 pandemic at different points in gestation on preterm birth.ObjectiveOur objective was to determine-among cohorts exposed to the early COVID-19 pandemic-whether observed counts of overall, early and moderately preterm birth fell outside the expected range.MethodsWe used de-identified, cross-sectional, national birth certificate data from 2014 to 2020. We used month and year of birth and gestational age to estimate month of conception for birth. We calculated the count of overall (

Approximately 0.7% of infants are born with congenital cytomegalovirus (CMV), making it the most common congenital infection. About 1 in 5 congenitally infected babies will suffer long-term sequelae, including sensorineural deafness, intellectual disability, and epilepsy. CMV infection is highly species-dependent, and the rhesus CMV (RhCMV) infection of rhesus monkey fetuses is the only animal model that replicates essential features of congenital CMV (cCMV) infection in humans, including placental transmission, fetal disease, and fetal loss. Using experimental data from RhCMV seronegative rhesus macaques inoculated with RhCMV in the late first to early second trimesters of pregnancy, we built and calibrated a mathematical model for the placental transmission of CMV. The model was then used to study the effect of the timing of inoculation, maternal immune suppression, and hyper-immune globulin infusion on the risk of placental transmission in the context of primary and reactivated chronic maternal CMV infection.

IntroductionAntenatal depression is highly prevalent and is associated with negative birth and neonatal outcomes. However, the mechanisms and causality behind these associations remain poorly understood as they are varied. Given the variability in whether associations are present, there is need to have context-specific data to understand the complex factors that go into these associations. This study aimed to assess the associations between antenatal depression and birth and neonatal outcomes among women attending maternity care in Harare, Zimbabwe.MethodsWe followed 354 pregnant women in second or third trimester, attending antenatal care services in two randomly selected clinics in Harare, Zimbabwe. Antenatal depression was assessed using the Structured Clinical Interview for DSM-IV. Birth outcomes included birth weight, gestational age at delivery, mode of delivery, Apgar score, and initiation of breastfeeding within one-hour postdelivery. Neonatal outcomes at six weeks postdelivery included infant's weight, height, illness, feeding methods and maternal postnatal depressive symptoms. The association between antenatal depression and categorical and continuous outcomes were assessed by logistic regression and point-biserial correlation coefficient, respectively. Multivariable logistic regression determined the confounding effects on statistically significant outcomes.ResultsPrevalence of antenatal depression was 23.7%. It was associated with low birthweight [AOR = 2.30 (95% CI: 1.08-4.90)], exclusive breastfeeding [AOR = 0.42 (95%CI: 0.25-0.73)] and postnatal depressive symptoms [AOR = 4.99 (95%CI: 2.81-8.85)], but not with any other birth or neonatal outcomes measured.ConclusionsThe prevalence of antenatal depression in this sample is high with significant associations demonstrated for birth weight, maternal postnatal depressive symptoms and infant feeding methods Effective management of antenatal depression is thus crucial to the promotion of maternal and child health.

BackgroundGlobally, almost 15 million infants are born prematurely each year, disproportionately affecting low and middle-income countries. In the absence of mother's milk, the World Health Organization recommends using donor human milk (DHM) due to its protective effect against necrotizing enterocolitis, a life-threatening intestinal disorder. The use of DHM is increasing globally, with many low and middle-income countries integrating donor milk banks into their public health strategies to reduce neonatal mortality, yet very little is known about the nutritional composition of DHM. Additional knowledge gaps include how DHM composition is influenced by milk banking practices, and whether preterm nutrient recommendations are achieved when DHM is used with commercially available fortifiers.MethodsWe designed a multi-site study with eight geographically diverse milk bank partners in high, middle, and low-income settings that will examine and compare a broad range of nutrients and bioactive factors in human milk from 600 approved milk bank donors around the world to create comprehensive, geographically diverse nutrient profiles for DHM. We will then simulate the random pooling of 2 to 10 donors to evaluate the impact of pooling as a potential strategy for milk banks to manage nutrient variability in DHM. Finally, we will evaluate whether commercially available fortifiers meet nutrient recommendations when used with DHM.DiscussionWe expect that results from this study will improve nutritional care globally for the growing number of preterm infants who receive donor human milk.

BackgroundGrowing evidence suggests low and high maternal hemoglobin (Hb) concentrations may have adverse consequences for maternal and child health. There remain questions on specific Hb thresholds to define anemia and high Hb as well as how cutoffs may vary by anemia etiology and timing of assessment.MethodsWe conducted an updated systematic review (using PubMed and Cochrane Review) on low (

Preterm birth is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous preterm birth, and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology and our transcriptomics studies suggest a role for placental maturity in idiopathic spontaneous preterm birth. It is known that placental DNA methylation changes over gestation. We hypothesized that if placental hypermaturity is present in our samples, we would observe a unique idiopathic spontaneous preterm birth DNA methylation profile potentially driving the gene expression differences we previously identified in our placental samples. Our results indicate the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions fitting the idiopathic spontaneous preterm birth specific (relative to the controls) profile were identified, indicating unusually high similarity in DNA methylation between idiopathic spontaneous preterm birth and term birth samples. We identified an additional 1,718 significantly methylated regions in our gestational age matched controls where the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern, again indicating a striking level of similarity between the idiopathic spontaneous preterm birth and term birth samples. Pathway analysis of these regions revealed differences in genes within the WNT and Cadherin signaling pathways, both of which are essential in placental development and maturation. Taken together, these data demonstrate that the idiopathic spontaneous preterm birth samples display a hypermature methylation signature than expected given their respective gestational age which likely impacts birth timing.

IntroductionChorioamnionitis is common in preterm birth and associated with a higher risk of intestinal inflammation and necrotizing enterocolitis. The intestinal inflammation influences the enteric nervous system development. We hypothesized that inflammation and innervation in the fetal ileum may be modified by chorioamnionitis induced by repeated challenge with lipopolysaccharide and/or preexisting Ureaplasma parvum infection at very low gestational age equivalent to 60% of term.Materials and methodsTime mated ovine fetuses were exposed by intraamniotic injections to chronic Ureaplasma parvum for 24 days and/or lipopolysaccharide for 7 days, 2 days, or 7 & 2 days before delivery at 94 +/-2 days of gestational age (term at approximately 150 days). Intestinal inflammation as well as structural changes of the enteric nervous system were assessed.ResultsLipopolysaccharide exposure increased CD3 and myeloperoxidase-positive cells (p < 0.05). Repetitive exposure to lipopolysaccharide or combined Ureaplasma parvum & lipopolysaccharide exposure increased intestinal inflammation (p < 0.05). The reduction of nuclei of neurons was most significant with repetitive lipopolysaccharide exposures but could be detected in all other intervention groups compared to the control group. Astrocyte-like glial cells increased if exposure to lipopolysaccharide was only 2 days before delivery or chronic exposure to Ureaplasma parvum existed beforehand (p < 0.05).DiscussionAfter exposure to chorioamnionitis induced by Ureaplasma parvum and/or lipopolysaccharide, inflammatory responses as well as structural changes of the enteric nervous system were more pronounced the longer and the more frequent the exposure to pro-inflammatory stimuli before birth. These changes may cause functional effects of clinical importance.

ObjectivesAs the social and legal acceptance of cannabis use grows, health professionals must understand and mitigate the impact of cannabis use in the perinatal period. Here we compare the prevalence of tobacco and cannabis use during and after pregnancy in California, a state that recently legalized cannabis use.MethodsMeasures of tobacco and cannabis use during and after pregnancy were obtained from California's Maternal and Infant Health Assessment, an annual population-based survey of California resident women with a live birth. To allow analysis of county-level variation, we pooled data from the 35 counties with the largest numbers of births from 2017 to 2019.ResultsCannabis use was more than twice as common as cigarette smoking among pregnant women (4.9% vs. 2.1%) in California. This difference was even more pronounced in some counties; for example, in Los Angeles, cannabis use was four times more prevalent than cigarette use. Either during or soon after birth, 7.3% of women in California reported cannabis use. Of those who smoked tobacco cigarettes prior to pregnancy, 73% quit before their third trimester of pregnancy, though 33.0% of these women reported a post-partum relapse in cigarette use.ConclusionsStates that have legalized cannabis must attend to the increasing prevalence of perinatal cannabis use, as well as concurrent use with tobacco and other substances. Efforts to support cannabis cessation should draw from successful public health approaches in tobacco control.

IntroductionDespite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.MethodsWe screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.ResultsWe screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.ConclusionsThis analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

BackgroundLittle research has been conducted on the impact of the coronavirus disease 2019 (COVID-19) pandemic on either birth outcomes or the ability of archival medical records to accurately capture these outcomes. Our study objective is thus to compare the prevalence of preterm birth, stillbirth, low birth weight (LBW), small for gestational age (SGA), congenital microcephaly, and neonatal bloodstream infection (NBSI) before and during the first wave of the COVID-19 pandemic in Kinshasa, Democratic Republic of Congo (DRC).MethodsWe conducted a facility-based retrospective cohort study in which identified cases of birth outcomes were tabulated at initial screening and subcategorized according to level of diagnostic certainty using Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) definitions. Documentation of any birth complications, delivery type, and maternal vaccination history were also evaluated. The prevalence of each birth outcome was compared in the pre-COVID-19 (i.e., July 2019 to February 2020) and intra-COVID-19 (i.e., March to August 2020) periods via two-sample z-test for equality of proportions.ResultsIn total, 14,300 birth records were abstracted. Adverse birth outcomes were identified among 22.0% and 14.3% of pregnancies in the pre-COVID-19 and intra-COVID-19 periods, respectively. For stillbirth, LBW, SGA, microcephaly, and NBSI, prevalence estimates were similar across study periods. However, the prevalence of preterm birth in the intra-COVID-19 period was significantly lower than that reported during the pre-COVID-19 period (8.6% vs. 11.5%, p

Intra-Uterine Growth Restriction (IUGR) is a risk factor for many adult-onset chronic diseases, such as diabetes and obesity. These diseases are associated with intestinal microbiome perturbations (dysbiosis). The establishment of an intestinal microbiome begins in utero and continues postnatally (PN). Hypercaloric diet-induced dysbiosis is a major driver of childhood obesity. We hypothesized that different postnatal diets superimposed on IUGR will alter the postnatal intestinal microbiome. We compared four experimental rat groups: (1) Ad lib fed regular chow diet pre- and postnatally (CON), (2-3) IUGR induced by maternal caloric restriction prenatally followed postnatally (PN) by either (2) the control diet (IUGR-RC) or (3) High-Fat-high-fructose (IUGR-HFhf) diet, and lastly (4) HFhf ad lib pre- and postnatally (HFhf). Fecal samples were collected from dams and male and female rat offspring at postnatal day 2, 21, and adult day 180 for 16S rRNA gene sequencing. Maternal diet induced IUGR led to dysbiosis of the intestinal microbiome at PN21. Postnatal HFhf diet significantly reduced microbial diversity and worsened dysbiosis reflected by an increased Gammaproteobacteria/Clostridia ratio. Dysbiosis arising from a mismatch between IUGR and a postnatal HFhf diet may contribute to increased risk of the IUGR offspring for subsequent detrimental health problems.