Growth patterns by birth size of preterm children born at 24-29 gestational weeks for the first 3 years.

BACKGROUND: Concerns are prevalent about preterm infant long-term growth regarding plotting low on growth charts at discharge, stunting, underweight, high body fat and subsequent cardiometabolic morbidities. OBJECTIVES: To examine (a) longitudinal growth patterns of extremely and very preterm infants to 3 years corrected age (CA) (outcome), categorised by their birthweight for gestational age: small, appropriate and large for gestational age (SGA, AGA and LGA, respectively) (exposure); and (b) the ability of growth faltering (<-2 z-scores) to predict suboptimal cognitive scores at 3 years CA. METHODS: Post-discharge head, length, weight and weight-4-length growth patterns of the PreM Growth cohort study infants born <30 weeks and < 1500 g, who had dietitian and multi-disciplinary support before and after discharge, were plotted against the World Health Organization growth standard. Infants with brain injuries, necrotising enterocolitis and bronchopulmonary dysplasia were excluded. RESULTS: Of the included 405 infants, the proportions of infants with anthropometric measures > - 2 z-scores improved with age. The highest proportions <-2 z-scores for length (24.2%) and weight (24.0%) were at 36 gestational weeks. The proportion with small heads was low by 0 months CA (1.8%). By 3 years CA, only a few children plotted lower than -2 z-scores for length, weight-4-length and weight (<6%). After zero months CA, high weight-4-length and body mass index > + 2 z-scores were rare (2.1% at 3 years CA). Those born SGA had higher proportions with shorter heights (16.7% vs. 5.2%) and lower weights (27.8% vs. 3.5%) at 3 years CA compared to those born AGA. The ability of growth faltering to predict cognitive scores was limited (AUROC 0.42, 95% CI 0.39, 0.45 to 0.52, 95% CI 0.41, 0.63). CONCLUSIONS: Although children born <30 weeks gestation without major neonatal morbidities plot low on growth charts at 36 weeks CA most catch up to growth chart curves by 3 years CA.

Expected and Desirable Preterm and Small Infant Growth Patterns.

Adequate nutrition is necessary for achieving optimal growth and neurodevelopment. Growth is a natural and expected process that happens concomitantly with rapid advancements in neurodevelopment. Serial weight, length, and head circumference growth measures are essential for monitoring development, although identifying pathological deviations from normal growth can pose challenges. Appropriate growth assessments require considerations that a range of sizes for length, head circumference, and weight are expected and appropriate. Because of genetic differences and morbidities, there is a considerable overlap between the growth of healthy infants and those with growth alterations. Parents tend to be over-concerned about children who plot low on growth charts and often need reassurance. Thus, the use of terms such as "poor" growth or growth "failure" are discouraged when growth is approximately parallel to growth chart curves even if their size is smaller than specific percentiles. No specific percentile should be set as a growth goal; individual variability should be expected. An infant's size at birth is important information that goes beyond the common use of prognostic predictions of appropriate compared with small or large for gestational age. The lower the birthweight, the lower the nutrient stores and the more important the need for nutrition support. Compared to term infants, preterm infants at term-equivalent age have a higher percentage of body fat, but this diminishes over the next months. Current research findings support expert recommendations that preterm infants should grow, after early postnatal weight loss, similar to the fetus and then term-born infants, which translates to growth approximately parallel to growth chart curves. There is no need for a trade-off between optimum cognition and optimum future health. Each high-risk infant needs individualized nutrition and growth assessments. This review aims to examine infant growth expectations and messaging for parents of preterm and term-born infants within the broader causal framework.

Lyophilized (freeze-dried) human milk for preterm infants: a scoping review.

Freeze-drying (FD), or lyophilization, is commonly used to preserve foods. FD offers potential to create a human milk-derived human milk fortifier, and an alternative to freeze-storing human milk. However, processing human milk is known to affect its components. This scoping review explores the effect of FD on the; macronutrient, micronutrient, vitamin, bioactive components, microbes and anti-microbial factors in human milk, and studies where lyophilized human milk has been given to newborn infants. 48 articles were identified after full text review. FD human milk reduces the fat globule size and as well as the quantity of enzymes, vitamin C and immunoglobulin. Common serum electrolyte disturbances have been reported when preterm infants' are fed FD human milk however it appears a promising method to avoid exposure of preterm infants' to cows' milk. Due to limited data, further studies exploring the safety and efficacy of FD human milk in preterm infants are needed.

Postnatal acetaminophen exposure and neurodevelopmental outcomes at 18-21 months corrected gestational age in preterm infants <29 weeks gestation: a retrospective cohort study.

BACKGROUND: Studies have reported prenatal acetaminophen exposure is associated with abnormal neurodevelopment. There is limited and conflicting data on neurodevelopmental outcomes following postnatal acetaminophen exposure. Our objective was to investigate the neurodevelopmental outcomes of preterm infants < 29 weeks gestation postnatally exposed to acetaminophen. METHODS: Retrospective cohort study of infants born between 2008 and 2017 at a tertiary care perinatal center. Exclusion criteria included chromosomal disorders, major congenital abnormalities, and congenital infections. The primary outcome was a composite score of <85 on the cognitive, language, or motor components of the Bayley Scales of Infant and Toddler Development, 3rd edition, assessed at 18 to 21 months corrected gestational age. Multivariate logistic regression was used to assess confounders. RESULTS: Of the 945 infants included in the study, 120 were in the acetaminophen group. There was no difference in any of Bayley-III cognitive, language or motor composite scores of < 85 between the two groups for postnatal acetaminophen exposure, adjusted odds ratios (aORs) 1.03, 95% CI 0.60-1.78, or days of acetaminophen use, aORs 1.10, 95% CI 0.93-1.29. CONCLUSIONS: There was no difference in neurodevelopmental outcome between the acetaminophen exposed and non-exposed groups. Our results need validation in larger cohorts. IMPACT: Animal research and cohort studies have suggested that prenatal acetaminophen exposure may be associated with an elevated risk of neurobehavioral abnormalities. However, there is limited and conflicting research on the impact of postnatal acetaminophen on neurodevelopment. The results of this study suggest that postnatal acetaminophen does not negatively impact neurodevelopment at 18 to 21 months in preterm infants born at <29 weeks gestational age. While these results need validation in larger and more longitudinal studies, this study provides reassurance for the use of postnatal acetaminophen in extremely preterm infants.

A Quality Improvement Initiative to Reduce Necrotizing Enterocolitis in Very Preterm Infants.

OBJECTIVE: To reduce the incidence of necrotizing enterocolitis (NEC) among very preterm infants in the Calgary Health Region to ≤2% within 2 years. METHODS: A multidisciplinary team developed key drivers for NEC. Targeted interventions included strategies to increase mothers' own milk (MOM), improve compliance with feeding regimens, standardize management of feeding intolerance, prevent intestinal microbial aberrations, and feed conservatively during blood transfusion and the treatment of patent ductus arteriosus. The outcome measure was NEC (≥ stage 2). Changes in NEC rates were examined among racial and ethnic groups. Process measures included MOM feeding at discharge, the difference between actual and expected time to reach full feeds, lowest hemoglobin, and the duration of empirical antibiotics. Growth, the rate of blood transfusion, and the duration of parenteral nutrition were balancing measures. The preintervention, intervention, and sustainment periods were January 2013 to June 2016, July 2016 to December 2018, and December 2018 to December 2021, respectively. RESULTS: We included 2787 infants born at ≤326/7 weeks' gestation (1105 preintervention, 763 during intervention, and 919 in sustainment). NEC decreased from 5.6% to 1.9%. Process measures indicated increased MOM feeding at discharge, improved compliance with feeding regimens, increased lowest hemoglobin levels, and shorter durations of empirical antibiotics. Balancing measures revealed improved weight Z-scores, shorter durations on parenteral nutrition, and increased rates of blood transfusion. CONCLUSIONS: Quality improvement initiatives to increase MOM, improve compliance with feeding regimens, feed conservatively during blood transfusion and treatment of patent ductus arteriosus, and prevent intestinal microbial aberrations were associated with reduced NEC.

Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial: a protocol for a multicentre, stepped-wedge cluster randomized trial.

BACKGROUND: Evidence-based Practice for Improving Quality (EPIQ) is a collaborative quality improvement method adopted by the Canadian Neonatal Network that led to decreased mortality and morbidity in very preterm neonates. The Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial aims to evaluate the impact of EPIQ collaborative quality improvement strategies in moderate and late preterm neonates in Alberta, Canada. METHODS: In a 4-year, multicentre, stepped-wedge cluster randomized trial involving 12 neonatal intensive care units (NICUs), we will collect baseline data with the current practices in the first year (all NICUs in the control arm). Four NICUs will transition to the intervention arm at the end of each year, with 1 year of follow-up after the last group transitions to the intervention arm. Neonates born at 32 + 0 to 36 + 6 weeks' gestation with primary admission to NICUs or postpartum units will be included. The intervention includes implementation of respiratory and nutritional care bundles using EPIQ strategies, including quality improvement team building, quality improvement education, bundle implementation, quality improvement mentoring and collaborative networking. The primary outcome is length of hospital stay; secondary outcomes include health care costs and short-term clinical outcomes. Neonatal intensive care unit staff will complete a survey in the first year to assess quality improvement culture in each unit, and a sample will be interviewed 1 year after implementation in each unit to evaluate the implementation process. INTERPRETATION: The ABC-QI Trial will assess whether collaborative quality improvement strategies affect length of stay in moderate and late preterm neonates. It will provide detailed population-based data to support future research, benchmarking and quality improvement. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT05231200.

Enteral long-chain polyunsaturated fatty acids and necrotizing enterocolitis: A systematic review and meta-analysis.

BACKGROUND: Preterm infants are at risk of long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Recent studies on high-dose DHA; n-3 LCPUFA in preterm infants suggested potential positive effects on cognitive outcomes but raised concerns about some increased neonatal morbidities. These studies and recent recommendations for DHA supplementation generated controversy owing to the lack of balance between DHA and arachidonic acid (ARA; n-6 LCPUFA). OBJECTIVES: To identify the effect of enteral supplementation of DHA, with and without ARA, on necrotizing enterocolitis (NEC) in very preterm infants. METHODS: A systematic review of randomized and controlled trials compared enteral LCPUFAs with placebo or no supplementation in very preterm infants. We searched PubMed, Ovid-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINHAL databases from inception to July 2022. Data were extracted in duplicate using a structured proforma. A meta-analysis and metaregression with random-effects models were used. The interventions evaluated were DHA alone vs. that combined with ARA, source of DHA, dose, and supplement delivery methods. Methodological qualities and risk of bias were assessed using the Cochrane risk-of-bias tool. RESULTS: Fifteen randomized clinical trials (RCTs) included 3963 very preterm infants with 217 cases of NEC. Supplementation with DHA alone increased NEC (2620 infants; RR: 1.56; 95% CI: 1.02, 2.39) with no evidence of heterogeneity (I2 = 0.0%, P = 0.46). Multiple metaregression revealed significant reduction in NEC when ARA was supplemented with DHA (aRR 0.42; 95% CI: 0.21, 0.88). The source of DHA, dose, and feeding type revealed no associations with NEC. Two RCTs supplemented high-dose DHA to lactating mothers. There was a significant increase in risk of NEC with this approach (1148 infants; RR: 1.92; 95% CI: 1.02, 3.61) with no evidence of heterogeneity (I2 = 0.0, P = 0.81). CONCLUSIONS: Supplementation with DHA alone may increase risk of NEC. Concurrent supplementation with ARA needs to be considered when adding DHA to preterm infants' diet.

Hindmilk as a Rescue Therapy in Very Preterm Infants with Suboptimal Growth Velocity.

Despite advances in neonatal nutrition, very preterm infants remain at increased risk of extrauterine growth faltering. This prospective study aimed to examine the effect of hindmilk, the milk at the end of a breast expression session, on growth and plasma fatty acids (FAs) of infants born <30 weeks' gestation who had been on full enteral feeds for ≥2 weeks and had a weight gain of <15 g/kg/day despite optimizing energy and protein intakes. Weight and plasma FAs were assessed before and two weeks after feeding hindmilk. Growth anthropometrics were assessed weekly for four weeks. Paired t-tests and multiple linear regression were used for statistical analyses of data from 34 infants and their 29 mothers. There was a significant increase in weight gain in the two weeks after feeding hindmilk (MD 3.9, 95%CI 1.2-6.5 g/kg/day). Weight Z-scores were larger at two weeks (MD 0.61, 95%CI 0.02-1.20) and onwards. Head circumference Z-scores were larger at three weeks (MD 0.83, 95%CI 0.20-1.47) and onwards. Plasma linoleic acid (LA) and α-linolenic acid (ALA) increased after feeding hindmilk. In conclusion, hindmilk may improve weight and head growth and increase LA and ALA in very preterm infants with suboptimal growth. A large randomized controlled trial is required to examine and validate the potential benefits of hindmilk.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

SMOFlipid Impact on Growth and Neonatal Morbidities in Very Preterm Infants.

The soybean oil, medium-chain triglycerides, olive oil, and fish oil lipid (SMOFlipid) is increasingly being used worldwide without definite evidence of its benefits. We examined the effect of SMOFlipid on growth velocity and neonatal morbidities in very preterm infants. Very preterm infants who received soybean-based lipid emulsion between January 2015 and 2018 were compared with those who received SMOFlipids between 2019 and January 2022 in our neonatal tertiary center. Linear regression analysis was conducted to analyze the association between type of lipid emulsion and growth velocity. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber−White) were applied to adjust for potential confounding factors. A total of 858 infants met our inclusion criteria. Of them, 238 (27.7%) received SMOFlipid. SMOFlipid was associated with lower growth velocity between birth and 36-week corrected gestational age compared with intralipid Δ weight z-score (adjusted mean difference (aMD) −0.67; 95% CI −0.69, −0.39). Subgroup analysis indicated that mainly male infants in the SMOFlipid−LE group had a lower Δ weight z-score compared to those in the intralipid group (p < 0.001), with no difference observed in females (p = 0.82). SMOFlipid was associated with a lower rate of bronchopulmonary dysplasia (BPD) (aRR 0.61; 95% CI 0.46, 0.8) and higher rate of late-onset sepsis compared with intralipid (aRR 1.44; 95% CI 1.22−1.69). SMOFlipid was associated with lower growth velocity and BPD but higher rate of late-onset sepsis­it is a double-edged sword.

Neonatal and Preterm Infant Growth Assessment.

The needs to assess preterm infant growth clinically differ from the needs to summarize growth for research. Clinically, growth assessments are used to understand individuals' growth relative to their individual genetic potential, morbidity status and nutrition care. Growth quantification for research purposes is used to quantify growth of groups using meaningful metrics. Historically, neonatology has lacked consistency in the use of growth metrics, over-used irrelevant categories and over-diagnosed growth failure. Understanding the numerous preterm infant expected growth patterns can help identify concerning growth.

Supplementation with a probiotic mixture accelerates gut microbiome maturation and reduces intestinal inflammation in extremely preterm infants.

Probiotics are increasingly administered to premature infants to prevent necrotizing enterocolitis and neonatal sepsis. However, their effects on gut microbiome assembly and immunity are poorly understood. Using a randomized intervention trial in extremely premature infants, we tested the effects of a probiotic product containing four strains of Bifidobacterium species autochthonous to the infant gut and one Lacticaseibacillus strain on the compositional and functional trajectory of microbiome. Daily administration of the mixture accelerated the transition into a mature, term-like microbiome with higher stability and species interconnectivity. Besides infant age, Bifidobacterium strains and stool metabolites were the best predictors of microbiome maturation, and structural equation modeling confirmed probiotics as a major determinant for the trajectory of microbiome assembly. Bifidobacterium-driven microbiome maturation was also linked to an anti-inflammatory intestinal immune milieu. This demonstrates that Bifidobacterium strains are ecosystem engineers that lead to an acceleration of microbiome maturation and immunological consequences in extremely premature infants.

Neonatal outcomes of twins <29 weeks gestation of mothers with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown. METHODS: Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infants <29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers. RESULTS: Of the 2414 eligible twin infants <29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59). Preterm twin infants born to mothers with HDP also had higher odds of mortality (AOR 2.02, 95% CI 1.23-3.32). There was no difference in other outcomes. CONCLUSION: Preterm twin infants <29 weeks gestation of HDP mothers have higher odds of severe ROP and mortality. IMPACT: Hypertensive disorders of pregnancy, associated with placental dysfunction, are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality.

Multi-strain probiotics for extremely preterm infants: a randomized controlled trial.

BACKGROUND: Effects of probiotics on intestinal microbiota and feeding tolerance remain unclear in extremely low-birth-weight (ELBW) infants. METHODS: ELBW infants were randomly assigned to receive probiotics or no intervention. Stool samples were collected prior to, 2 and 4 weeks after initiation, and 2 weeks after probiotics cessation for infants in the probiotics group, and at matched postnatal age time points for infants in the control group. RESULTS: Of the 102 infants assessed for eligibility, sixty-two were included. Infants who received probiotics reached full enteral feeds sooner (Mean difference (MD) -1.8; 95% CI:-3.7 to -0.01 day), had a tendency toward lower incidence of hematochezia before hospital discharge (22.6% vs 3.2%; P = 0.053), and were less likely to require extensively hydrolyzed- or amino acids-based formulas to alleviate signs of cow's milk protein intolerance in the first 6 months of life (19.4% vs 51.6%; P = 0.008). Infants on probiotics were more likely to receive wide-spectrum antibiotics (64.5% vs 32.2%; P = 0.01). Multi-strain probiotics resulted in significant increase in fecal Bifidobacterium (P < 0.001) and Lactobacillus (P = 0.005), and marked reduction in fecal candida abundance (P = 0.04). CONCLUSION: Probiotics sustained intestinal Bifidobacterium and reduced time to achieve full enteral feeds in extremely preterm infants. Probiotics might improve tolerance for cow's milk protein supplements. CLINICAL TRIAL REGISTRATION: This trial has been registered at www. CLINICALTRIALS: gov (identifier NCT03422562). IMPACT: Probiotics may help extremely preterm infants achieve full enteral feeds sooner. Probiotics may improve tolerance for cow's milk protein supplements. Multi-strain probiotics can sustain intestinal Bifidobacterium and Lactobacillus until hospital discharge.

Rates and Determinants of Home Nasogastric Tube Feeding in Infants Born Very Preterm.

OBJECTIVE: To examine rates and determinants of home nasogastric (NG)-tube feeding at hospital discharge in a cohort of very preterm infants within the Canadian Neonatal Network (CNN). STUDY DESIGN: This was a population-based cohort study of infants born <33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2010, and December 31, 2018. We excluded infants who had major congenital anomalies, required gastrostomy-tube, or were discharged to non-CNN facilities. Multivariable logistic regression analysis was used to identify independent determinants of home NG-tube feeding at hospital discharge. RESULTS: Among the 13 232 infants born very preterm during the study period, 333 (2.5%) were discharged home to receive NG-tube feeding. Rates of home NG-tube feeding varied across Canadian NICUs, from 0% to 12%. Determinants of home NG-tube feeding were gestational age (aOR 0.94 per each gestational week increase, 95% CI 0.88-0.99); duration of mechanical ventilation (aOR 1.02 per each day increase, 95% CI 1.01-1.02); high illness severity at birth (aOR 1.32, 95% CI 1.01-1.74); small for gestational age (aOR 2.06, 95% CI 1.52-2.78); male sex (aOR 0.61, 95% CI 0.49-0.77); severe brain injury (aOR 1.60, 95% CI 1.10-2.32); and bronchopulmonary dysplasia (aOR 2.22, 95% CI 1.67-2.94). CONCLUSIONS: Rates of home NG-tube feeding varied widely between Canadian NICUs. Higher gestational age and male sex reduced the odds of discharge home to receive NG-tube feeding; and in contrast small for gestational age, severe brain injury, prolonged duration on mechanical ventilation and bronchopulmonary dysplasia increased the odds.

Effect of enteral zinc supplementation on growth and neurodevelopment of preterm infants: a systematic review and meta-analysis.

OBJECTIVE: To evaluate effect of enteral zinc supplementation on growth and neurodevelopmental outcomes of preterm infants. STUDY DESIGN: A systematic review and meta-analysis of randomized-controlled trials (RCTs) examining growth and neurodevelopmental outcomes after zinc supplementation in preterm infants. RESULTS: Of eight RCTs involving 742 infants included, seven reported growth anthropometrics at 3-6 months corrected age (CA) and two reported neurodevelopmental outcomes at 6-12 months CA. Zinc supplementation was associated with increased weight z-score (weighted mean difference (WMD) = 0.50; 95% CI 0.23-0.76, heterogeneity I2 = 89.1%; P < 0.01), length z-score (WMD = 1.12; 95% CI 0.63-1.61, heterogeneity I2 = 96.0%; P < 0.01) and motor developmental score (WMD = 9.54; 95% CI 6.6-12.4 heterogeneity I2 = 0%; P = 0.52). There was no effect on head circumference and total developmental score. Evidence is "moderate" certainty for weight and length and "very low" certainty for neurodevelopment. CONCLUSION: Zinc supplementation may enhance weight gain and linear growth in preterm infants. There is a lack of data about relationship between zinc supplementation and neurodevelopment.

Impact of Lockdown Measures during COVID-19 Pandemic on Pregnancy and Preterm Birth.

OBJECTIVE: The objective of this study is to assess the effect of the lockdown measures during the coronavirus disease 2019 (COVID-19) pandemic on pregnancy outcomes of women who were not affected by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: We used data from the perinatal health program and neonatal databases to conduct a cohort analysis of pregnancy outcomes during the COVID-19 lockdown in the Calgary region, Canada. Rates of preterm birth were compared between the lockdown period (March 16 to June 15, 2020) and the corresponding pre-COVID period of 2015 to 2019. We also compared maternal and neonatal characteristics of preterm infants admitted to neonatal intensive care units (NICUs) in Calgary between the two periods. FINDINGS: A total of 4,357 and 24,160 live births occurred in the lockdown and corresponding pre-COVID period, respectively. There were 366 (84.0 per 1,000 live births) and 2,240 (92.7 per 1,000 live births) preterm births in the lockdown and corresponding pre-COVID period, respectively (p = 0.07). Rates of very preterm and very-low-birth-weight births were lower in the lockdown period compared with the corresponding pre-COVID period (11.0 vs. 15.6 and 9.0 vs. 14.4 per 1,000 live births, p = 0.02 and p = 0.005, respectively). There was no difference in spontaneous stillbirth between the two periods (3.7 vs. 4.1 per 1,000 live birth, p = 0.71). During the lockdown period, the likelihood of multiple births was lower (risk ratio [RR] 0.73, 95% confidence interval [CI]: 0.60-0.88), while gestational hypertension and clinical chorioamnionitis increased (RR 1.24, 95%CI: 1.10-1.40; RR 1.33, 95%CI 1.10-1.61, respectively). CONCLUSION: Observed rates of very preterm and very-low-birth-weight births decreased during the COVID-19 lockdown. Pregnant women who delivered during the lockdown period were diagnosed with gestational hypertension and chorioamnionitis more frequently than mothers in the corresponding pre-COVID period. KEY POINTS: · Lockdown measures to reduce COVID-19 transmission were associated with a lower rate of preterm birth.. · Mental and physical wellbeing of pregnant women were significantly affected by the lockdown measures.. · A comprehensive public health plan to relieve psychosocial stress during pregnancy is required..

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.

Critical examination of relationships between early growth and childhood overweight in extremely preterm infants.

OBJECTIVES: To identify the prevalence and risk factors for childhood overweight and obesity (OWO) at 3-year corrected age in children born <1500 g <29 weeks gestation. STUDY DESIGN: A multicentre retrospective cohort study for preterm infants admitted to neonatal intensive care units between 2001 and 2014. RESULTS: Data were available for 911 (89.4%) of the 1019 infants who met the inclusion criteria. Of them, 22 (2.4%) had OWO. There were no associations between OWO and being small for gestational age (RR = 1.3, 95% confidence interval (CI): 0.3-5.4) or weight <10th percentile at 36 weeks (RR = 1.1, 95% CI: 0.4-2.8). OWO was associated with low maternal education (RR = 7.4, 95% CI: 2.1-26), maternal diabetes (RR = 5.2, 95% CI: 1.9-15) and neonatal brain injury (RR = 4.9, 95% CI: 1.8-14). Adjusting for concurrent child weight at 3 years of age resulted in an overadjustment bias. CONCLUSION: Small size at birth or at 36 weeks gestation in extremely preterm infants is not associated with increased risk of early childhood overgrowth or obesity. CLINICAL TRIAL REGISTRATION: NCT03064022.