Bacteroides-dominant gut microbiome of late infancy is associated with enhanced neurodevelopment.

Dysbiosis of gut microbiota has been retrospectively linked to autism spectrum disorders but the temporal association between gut microbiota and early neurodevelopment in healthy infants is largely unknown. We undertook this study to determine associations between gut microbiota at two critical periods during infancy and neurodevelopment in a general population birth cohort.Here, we analyzed data from 405 infants (199 females) from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study. Neurodevelopmental outcomes were objectively assessed using the Bayley Scale of Infant Development (BSID-III) at 1 and 2 years of age. Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at a mean age of 4 and 12 months.Using clustering methods, we identified three groups of infants based on relative abundance of gut microbiota at 12 months: Proteobacteria-dominant cluster (22.4% higher abundance at 12 months), Firmicutes-dominant cluster (46.0% higher abundance at 12 months) and Bacteroidetes-dominant cluster (31.6% higher abundance at 12 months). Relative to the Proteobacteria-dominant cluster, the Bacteroidetes-dominant cluster was associated with higher scores for cognitive (4.8 points; FDRp = .02), language (4.2 points; FDRp≤0.001), and motor (3.1 points; FDRp = .03) development at age 2 in models adjusted for covariates. When stratified by sex, only male infants with a Bacteroidetes-dominant microbiota had more favorable cognitive (5.9 points, FDRp = .06) and language (7.9 points; FDRp≤0.001) development. Genus Bacteroides abundance in gut microbiota was positively correlated with cognitive and language scores at age 2. Fully adjusted linear mixed model analysis revealed a positive association between Bacteroidetes-dominant cluster and change in cognitive and language performance from 1 to 2 years, predominantly among males. No associations were evident between 4-month microbiota clusters and BSID-II scores. Noteworthy is that enhanced sphingolipid synthesis and metabolism, and antagonism or competition between Bacteroides and Streptococcus were characteristic of a Bacteroidetes-dominant gut microbiota.This study found strong evidence of positive associations between Bacteroidetes gut microbiota in late infancy and subsequent neurodevelopment, most prominently among males but not females.

From Birth to Overweight and Atopic Disease: Multiple and Common Pathways of the Infant Gut Microbiome.

BACKGROUND & AIMS: Few studies, even those with cohort designs, test the mediating effects of infant gut microbes and metabolites on the onset of disease. We undertook such a study. METHODS: Using structural equation modeling path analysis, we tested directional relationships between first pregnancy, birth mode, prolonged labor and breastfeeding; infant gut microbiota, metabolites, and IgA; and childhood body mass index and atopy in 1667 infants. RESULTS: After both cesarean birth and prolonged labor with a first pregnancy, a higher Enterobacteriaceae/Bacteroidaceae ratio at 3 months was the dominant path to overweight; higher Enterobacteriaceae/Bacteroidaceae ratios and Clostridioides difficile colonization at 12 months were the main pathway to atopic sensitization. Depletion of Bifidobacterium after prolonged labor was a secondary pathway to overweight. Influenced by C difficile colonization at 3 months, metabolites propionate and formate were secondary pathways to child outcomes, with a key finding that formate was at the intersection of several paths. CONCLUSIONS: Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization.

Preeclampsia is not associated with elevated muscle sympathetic reactivity.

To determine whether increased chemoreflex tonic activity is associated with augmented muscle sympathetic nervous system activity (MSNA) in women diagnosed with preeclampsia. Women with preeclampsia (n = 19; 32 ± 5 yr old, 31 ± 3 wk of gestation) were matched by age and gestational age with pregnant women (controls, n = 38, 32 ± 4 yr old, 31 ± 4 wk gestation; 2:1 ratio). MSNA (n = 9 preeclampsia) was assessed during baseline, peripheral chemoreflex deactivation (hyperoxia), and a cold pressor test (CPT). Baroreflex gain and diastolic blood pressure at which there is a 50% likelihood of MSNA occurring (T50) and plasma noradrenaline concentrations were measured. Baseline mean arterial pressure (MAP: 106 ± 11 vs. 87 ± 10 mmHg, P < 0.0001), noradrenaline concentrations (498 ± 152 pg/mL vs. 326 ± 147, P = 0.001), and T50 (79 ± 7 vs. 71 ± 9 mmHg, P = 0.02) were greater in women with preeclampsia than in controls. However, baseline MSNA (burst incidence [BI]: 41 ± 16 vs. 45 ± 13 bursts/100 hb, P = 0.4) was not different between groups. Responses to hyperoxia (ΔBI -5 ± 7 vs. -1 ± 8 bursts/100 hb, P = 0.1; ΔMAP -1 ± 3 vs. -2 ± 3 mmHg, P = 0.7) and CPT (ΔBI 15 ± 7 vs. 12 ± 11 bursts/100 hb, P = 0.6; ΔMAP 10 ± 4 vs. 12 ± 11 mmHg, P = 0.6) were not different between groups. Our findings question the assumption that increased MSNA contributes to hypertension in women with preeclampsia. The chemoreflex does not appear to contribute to an increase in MSNA in women with preeclampsia.NEW & NOTEWORTHY We wanted to determine whether increased chemoreflex tonic activity is associated with augmented muscle sympathetic nervous system activity (MSNA) in women diagnosed with preeclampsia. The chemoreflex does not contribute to increased MSNA in women with preeclampsia. Our data also challenge the belief that preeclampsia is associated with sympathetic neural hyperactivity. Thus, targeting sympathetic neural hyperactivity as therapeutic strategy is unlikely to be the most efficacious approach to treatment and management.

Physical Activity in Pregnancy Is Associated with Increased Flow-mediated Dilation.

PURPOSE: To determine the role of moderate-to-vigorous physical activity (MVPA) and sedentary behavior in flow-mediated dilation (FMD) and glucose metabolism during late pregnancy. METHODS: Seventy normotensive, euglycemic pregnant women (31.6 ± 2.9 yr) in their third trimester (28-39 wk) were recruited. After a fasted blood sample; FMD was measured (brachial artery Doppler ultrasonography, normalized for the shear stimulus [area under the curve]). Anterograde and retrograde shear rate were estimated. Physical activity (MVPA) and sedentary behavior were assessed via accelerometry for seven consecutive days (Actigraph wGT3X-BT). We categorized the women as active (>150 min·wk) or inactive (<150 min·wk) according to their accelerometry data. Data were corrected for age and gestational age. RESULTS: On average, women were sedentary 67.1% ± 8.2% of their waking hours. Active pregnant women (>150 min·wk MVPA, n = 32) engaged in 266.7 ± 99.3 min·wk MVPA, whereas inactive pregnant women (<150 min·wk MVPA, n = 38) engaged in 76.1 ± 42.5 min·wk MVPA. The FMD response (normalized to the magnitude of shear stress stimulus) was greater in active compared with inactive pregnant women (6.5 ± 4.4 a.u. vs 3.9 ± 3.5 a.u.; F = 4.619; P = 0.005). The MVPA in active pregnant women was inversely correlated with insulin concentrations (r = -0.556; P = 0.03). In inactive pregnant women, higher amounts of sedentary behavior were associated with lower amounts of retrograde shear rate (r = 0.504; P = 0.02), retrograde blood flow (r = 0.499; P = 0.02), and retrograde velocity (r = 0.508; P = 0.02) during baseline, but not correlated with the FMD response. CONCLUSIONS: Engaging in MVPA during pregnancy is associated with improved FMD and a lower insulin concentration. Sedentary behavior was not associated with FMD responses.

Blunted sympathetic neurovascular transduction during normotensive pregnancy.

KEY POINTS: Normotensive pregnancy is associated with elevated sympathetic nervous system activity yet normal or reduced blood pressure. It represents a unique period of apparent healthy sympathetic hyperactivity. The present study models the blood pressure and heart rate (ECG R-R interval) responses to fluctuations in sympathetic nervous system activity aiming to understand neurocardiovascular transduction. The reported data clearly demonstrate that transduction of sympathetic nervous system signalling to systemic cardiovascular outcomes is reduced in normotensive pregnancy. These data are important for understanding how blood pressure regulation adapts during normotensive pregnancy and set the foundation for exploring similar mechanisms in hypertensive pregnancies. ABSTRACT: Previously, we described sympathetic nervous system hyperactivity yet decreased blood pressure responses to stress in normotensive pregnancy. To address the hypothesis that pregnant women have blunted neurocardiovascular transduction we assessed the relationship between spontaneous bursts of sympathetic nerve activity (SNA) and fluctuations in mean arterial blood pressure and R-R interval. Resting SNA, blood pressure and ECG were obtained in pregnant (third trimester, n = 18) and non-pregnant (n = 18) women matched for age and pre-/non-pregnant body mass index. Custom software modelled beat-by-beat pressure (photoplethysmography) and R-R interval in relation to sequences of SNA bursts and non-bursts (peroneal microneurography). Sequences were grouped by the number of bursts and non-bursts [singlets, doublets, triplets and quadruplet (four or more)] and mean blood pressure and R-R interval were tracked for 15 subsequent cardiac cycles. Similar sequences were overlaid and averaged. Peak mean pressure in relation to sequences of SNA was reduced in pregnant vs. non-pregnant women (doublets: 1.6 ± 1.1 mmHg vs. 3.6 ± 3.1 mmHg, P < 0.05; triplets: 2.4 ± 1.2 mmHg vs. 3.4 ± 2.1 mmHg, P < 0.05; quadruplets: 3.0 ± 1.0 mmHg vs. 5.5 ± 3.7 mmHg, P < 0.05). The nadir R-R interval following burst sequences was also smaller in pregnant vs. non-pregnant women (singlets: -0.01 ± 0.01 s vs. -0.04 ± 0.04 s, P < 0.05; doublets: -0.02 ± 0.03 s vs. -0.05 ± 0.04 s, P < 0.05; triplets: -0.02 ± 0.01 s vs. -0.07 ± 0.04 s, P < 0.05; quadruplets: -0.01 ± 0.01 s vs. -0.09 ± 0.09 s, P < 0.05). There were no differences between groups in the mean arterial pressure and R-R interval responses to non-burst sequences. Our data clearly indicate blunted systemic neurocardiovascular transduction during normotensive pregnancy. We propose that blunted transduction is a positive adaptation protecting pregnant women from the cardiovascular consequences of sympathetic hyperactivity.

Maternal Physical Activity Is Associated With Improved Blood Pressure Regulation During Late Pregnancy.

BACKGROUND: Cardiovagal baroreflex gain (cBRG) reflects an individual's ability to buffer swings in blood pressure. It is not well understood how this mechanism is influenced by physical activity in pregnancy. Because pregnant women tend to engage in low levels of moderate-to-vigorous physical activity (MVPA) and high levels of sedentary behaviour, we sought to determine the influence of MVPA and sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy. METHODS: Fifty-eight third trimester (31.9 ± 3.0 weeks) normotensive pregnant women (31.2 ± 2.8 years) were tested. Heart rate (electrocardiogram) and blood pressure (systolic blood pressure and MAP; finger photoplethysmography) were collected on a beat-by-beat basis, and averaged over 3 minutes of rest. Spontaneous cBRG was calculated as the slope of the relationship between fluctuations in systolic blood pressure and heart rate. Objective measures of MVPA and sedentary behaviour were collected over a 7-day period using an ActiGraph accelerometer (model wGTX3-BT; ActiGraph LLC, Pensacola, FL). RESULTS: Participants spent 67.5 ± 7.9% of waking hours engaged in sedentary behaviour, and performed 68.6 ± 91.9 minutes of MVPA per week. Sedentary behaviour was not related to cBRG (r = -0.035; P = 0.793) or MAP (r = -0.033; P = 0.803). However, MVPA was positively associated with cBRG (r = 0.315; P = 0.016), but not MAP (r = -0.115; P = 0.389). The association between MVPA and cBRG remained significant after controlling for age, pre-pregnancy body mass index, gestational age, and wear time (r = 0.338; P = 0.013), indicating that women who engaged in greater amounts of MVPA showed increased cBRG. CONCLUSIONS: Our data suggest that increased MVPA, but not necessarily reduced sedentary behaviour, might be beneficial for reflex control of blood pressure during pregnancy.

Cesarean Section, Formula Feeding, and Infant Antibiotic Exposure: Separate and Combined Impacts on Gut Microbial Changes in Later Infancy.

Established during infancy, our complex gut microbial community is shaped by medical interventions and societal preferences, such as cesarean section, formula feeding, and antibiotic use. We undertook this study to apply the significance analysis of microarrays (SAM) method to quantify changes in gut microbial composition during later infancy following the most common birth and postnatal exposures affecting infant gut microbial composition. Gut microbiota of 166 full-term infants in the Canadian Healthy Infant Longitudinal Development birth cohort were profiled using 16S high-throughput gene sequencing. Infants were placed into groups according to mutually exclusive combinations of birth mode (vaginal/cesarean birth), breastfeeding status (yes/no), and antibiotic use (yes/no) by 3 months of age. Based on repeated permutations of data and adjustment for the false discovery rate, the SAM statistic identified statistically significant changes in gut microbial abundance between 3 months and 1 year of age within each infant group. We observed well-known patterns of microbial phyla succession in later infancy (declining Proteobacteria; increasing Firmicutes and Bacteroidetes) following vaginal birth, breastfeeding, and no antibiotic exposure. Genus Lactobacillus, Roseburia, and Faecalibacterium species appeared in the top 10 increases to microbial abundance in these infants. Deviations from this pattern were evident among infants with other perinatal co-exposures; notably, the largest number of microbial species with unchanged abundance was seen in gut microbiota following early cessation of breastfeeding in infants. With and without antibiotic exposure, the absence of a breast milk diet by 3 months of age following vaginal birth yielded a higher proportion of unchanged abundance of Bacteroidaceae and Enterobacteriaceae in later infancy, and a higher ratio of unchanged Enterobacteriaceae to Alcaligenaceae microbiota. Gut microbiota of infants born vaginally and exclusively formula fed became less enriched with family Veillonellaceae and Clostridiaceae, showed unchanging levels of Ruminococcaceae, and exhibited a greater decline in the Rikenellaceae/Bacteroidaceae ratio compared to their breastfed, vaginally delivered counterparts. These changes were also evident in cesarean-delivered infants to a lesser extent. The clinical relevance of these trajectories of microbial change is that they culminate in taxon-specific abundances in the gut microbiota of later infancy, which we and others have observed to be associated with food sensitization.

No. 347-Obstetric Management at Borderline Viability.

OBJECTIVE: The primary objective of this guideline was to develop consensus statements to guide clinical practice and recommendations for obstetric management of a pregnancy at borderline viability, currently defined as prior to 25+6 weeks. INTENDED USERS: Clinicians involved in the obstetric management of women whose fetus is at the borderline of viability. TARGET POPULATION: Women presenting for possible birth at borderline viability. EVIDENCE: This document presents a summary of the literature and a general consensus on the management of pregnancies at borderline viability, including maternal transfer and consultation, administration of antenatal corticosteroids and magnesium sulfate, fetal heart rate monitoring, and considerations in mode of delivery. Medline, EMBASE, and Cochrane databases were searched using the following keywords: extreme prematurity, borderline viability, preterm, pregnancy, antenatal corticosteroids, mode of delivery. The results were then studied, and relevant articles were reviewed. The references of the reviewed studies were also searched, as were documents citing pertinent studies. The evidence was then presented at a consensus meeting, and statements were developed. VALIDATION METHODS: The content and recommendations were developed by the consensus group from the fields of Maternal-Fetal Medicine, Neonatology, Perinatal Nursing, Patient Advocacy, and Ethics. The quality of evidence was rated using criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (reference 1). The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. METHODS: The quality of evidence was rated using the criteria described in the Grading of Recommendations, Assessment, Development, and Evaluation methodology framework. The interpretation of strong and weak recommendations is described later. The Summary of Findings is available upon request. BENEFITS, HARMS, AND COSTS: A multidisciplinary approach should be used in counselling women and families at borderline viability. The impact of obstetric interventions in the improvement of neonatal outcomes is suggested in the literature, and if active resuscitation is intended, then active obstetric interventions should be considered. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. SPONSORS: This guideline was developed with resources funded by the Society of Obstetricians and Gynaecologists of Canada and the Women and Babies Program at Sunnybrook Health Sciences Centre.

Muscle sympathetic nerve activity and volume-regulating factors in healthy pregnant and nonpregnant women.

Healthy, normotensive human pregnancies are associated with striking increases in both plasma volume and vascular sympathetic nerve activity (SNA). In nonpregnant humans, volume-regulatory factors including plasma osmolality, vasopressin, and the renin-angiotensin-aldosterone system have important modulatory effects on control of sympathetic outflow. We hypothesized that pregnancy would be associated with changes in the relationships between SNA (measured as muscle SNA) and volume-regulating factors, including plasma osmolality, plasma renin activity, and arginine vasopressin (AVP). We studied 46 healthy, normotensive young women (23 pregnant and 23 nonpregnant). We measured SNA, arterial pressure, plasma osmolality, plasma renin activity, AVP, and other volume-regulatory factors in resting, semirecumbent posture. Pregnant women had significantly higher resting SNA (38 ± 12 vs. 23 ± 6 bursts/min in nonpregnant women), lower osmolality, and higher plasma renin activity and aldosterone (all P < 0.05). Group mean values for AVP were not different between groups [4.64 ± 2.57 (nonpregnant) vs. 5.17 ± 2.03 (pregnant), P > 0.05]. However, regression analysis detected a significant relationship between individual values for SNA and AVP in pregnant (r = 0.71, P < 0.05) but not nonpregnant women (r = 0.04). No relationships were found for other variables. These data suggest that the link between AVP release and resting SNA becomes stronger in pregnancy, which may contribute importantly to blood pressure regulation in healthy women during pregnancy.NEW & NOTEWORTHY Sympathetic nerve activity and blood volume are both elevated during pregnancy, but blood pressure is usually normal. Here, we identified a relationship between vasopressin and sympathetic nerve activity in pregnant but not nonpregnant women. This may provide mechanistic insights into blood pressure regulation in normal pregnancy and in pregnancy-related hypertension.

Post-Policy Implementation Review of Rapid Fetal Fibronectin (fFN) Testing for Preterm Labour in Alberta.

OBJECTIVES: In 2006, the Alberta Ministry of Health issued a policy to implement fetal fibronectin (fFN) testing as a publicly funded service for pregnant women. The goals were to reduce maternity health care utilization and unnecessary treatment, which would result in cost-savings for the health system by more accurately diagnosing false preterm labour. We conducted a post-policy implementation review to determine whether the policy implementation achieved its goals. METHODS: We assessed the impacts of fFN testing on clinical decision-making for ambulance transfer, hospital admission, and length of hospital stay by comparing these variables between the tested and untested patients. This post-implementation analysis was conducted separately for inpatients and outpatients and for true and false preterm labour, using multilevel regressions with episodes or visits being nested within patients. We then assessed the impact of fFN testing on costs to the health system by using decision-tree models populated with actual data and results from the regressions. RESULTS: The additional information, provided by fFN testing, influenced clinical decision-making. However, physicians placed a greater significance on positive test results than on negative results, which resulted in an inadvertent increase in health care utilization. After including the costs of fFN testing, the total cost to the system increased by $4.2 million (in 2014 Canadian dollars) between 2008 and 2013, with contributions of $700 000 for false labour and $3.5 million for true preterm labour. CONCLUSION: The policy to adopt fFN testing in Alberta did not achieve the intended aims of reducing unnecessary health care utilization to achieve cost-savings for the health system. There was an inherent tendency to err on the side of caution, and physicians were influenced more by positive test results.

Regulation of sympathetic nerve activity during the cold pressor test in normotensive pregnant and nonpregnant women.

Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001). Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls. Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04). However, neurovascular transduction during peak cold pressor-induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006). Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation. These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor-induced sympathoexcitation.

Sympathetic baroreflex gain in normotensive pregnant women.

Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.

Perinatal antibiotic exposure of neonates in Canada and associated risk factors: a population-based study.

OBJECTIVE: To describe neonatal antibiotic exposures occurring immediately before and after birth and their associated risk factors. METHODS: A retrospective review of the hospital charts of 449 mother-neonate pairs enrolled in the Canadian Healthy Infant Longitudinal Development national birth-cohort study was conducted at two tertiary hospitals and one rural hospital in Manitoba, Canada. The main outcome measures included the following: maternal and neonatal antibiotic use during the perinatal period; indications for antibiotic use, including suspected neonatal sepsis, maternal group B Streptococcus (GBS), premature rupture of membranes and caesarean-section; maternal health status, focusing on gestational hypertension, gestational diabetes, obesity and primigravida pregnancies. RESULTS: During the perinatal period, 45.0% of neonates were exposed to antibiotics. Intravenous penicillin G (17%) and cefazolin (16%) were the most commonly administered intrapartum antibiotics. Colonization with GBS was confirmed in 21.2% of women and treated with antibiotics in 86% of cases. Overweight women and women with hypertension were significantly more likely to receive intrapartum antibiotics for caesarean section or GBS prophylaxis. Antibiotic treatment of the neonate was highest following emergency caesarean section (12%) or unknown maternal GBS status (20%). CONCLUSIONS: Neonates in Canada are routinely exposed to antibiotics during the perinatal period.

Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months.

BACKGROUND: The gut microbiota is essential to human health throughout life, yet the acquisition and development of this microbial community during infancy remains poorly understood. Meanwhile, there is increasing concern over rising rates of cesarean delivery and insufficient exclusive breastfeeding of infants in developed countries. In this article, we characterize the gut microbiota of healthy Canadian infants and describe the influence of cesarean delivery and formula feeding. METHODS: We included a subset of 24 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mode of delivery was obtained from medical records, and mothers were asked to report on infant diet and medication use. Fecal samples were collected at 4 months of age, and we characterized the microbiota composition using high-throughput DNA sequencing. RESULTS: We observed high variability in the profiles of fecal microbiota among the infants. The profiles were generally dominated by Actinobacteria (mainly the genus Bifidobacterium) and Firmicutes (with diverse representation from numerous genera). Compared with breastfed infants, formula-fed infants had increased richness of species, with overrepresentation of Clostridium difficile. Escherichia-Shigella and Bacteroides species were underrepresented in infants born by cesarean delivery. Infants born by elective cesarean delivery had particularly low bacterial richness and diversity. INTERPRETATION: These findings advance our understanding of the gut microbiota in healthy infants. They also provide new evidence for the effects of delivery mode and infant diet as determinants of this essential microbial community in early life.

Fetal lung-to-liver signal intensity ratio at MR imaging: development of a normal scale and possible role in predicting pulmonary hypoplasia in utero.

PURPOSE: To define retrospectively a normal range for lung-to-liver signal intensity ratio (LLSIR) in fetuses of 16-40 weeks gestation by using half-Fourier single-shot turbo spin-echo magnetic resonance (MR) imaging. MATERIALS AND METHODS: Approval from the regional ethics review board for retrospective evaluation was obtained, and informed consent was waived. Retrospective analysis and follow-up of 157 pregnant women who underwent MR imaging over the past 4 years were performed. Seventy-four fetuses were subsequently identified as having clinically normal lung function or normal lung morphologic features at autopsy. A total of 141 normal lungs were analyzed, and the LLSIR was calculated from images on an MR workstation. A mixed-effects statistical model was applied, and 95% prediction intervals were calculated. Ten fetuses with hypoplastic lungs at autopsy were also evaluated. RESULTS: Plotting LLSIR against gestational age demonstrated that, according to the fitted mean curve, the signal intensity ratio was higher with more advanced gestational age. Statistical modeling suggests a quadratic relationship between gestational age and LLSIR. For fetuses in the normal population, the LLSIR ranged from 1.52 at 21 weeks gestation to 4.31 at 34 weeks gestation. For all hypoplastic lungs in fetuses at or beyond 25 weeks gestation, the LLSIR was outside the lower bound of the 95% prediction interval for the normal population. The distinction between hypoplastic lungs and normal lungs at less than 25 weeks gestation is less definitive. CONCLUSION: This study provides a normal scale with a 95% prediction interval for LLSIR.

Updating reference values for placental weights in Northern Alberta.

OBJECTIVE: The purpose of this study was to establish normal parameters for placental weights and fetal/placental weight ratios. STUDY DESIGN: Placentas (2402) from uncomplicated singleton deliveries at the Royal Alexandra Hospital (Edmonton, Alberta) were collected from 1997 to 1998 and weighed after fixation. The nonparametric Mann-Whitney test was applied. RESULTS: New reference values were developed for fixed placental weights. Placentas at the 90th percentile were 50 to 100 g heavier than previously reported. Fetal/placental weight ratios at term were similar to published values. CONCLUSION: The new placental weight reference values from our institution represent a recent and local population. New values may partly reflect parallel increases in term birth weights.