Glycemic control and neonatal outcomes in twin pregnancies with gestational diabetes mellitus.

BACKGROUND: Preliminary data suggest that strict glycemic control in twin pregnancies with gestational diabetes mellitus may not improve outcomes but might increase the risk of fetal growth restriction. OBJECTIVE: This study aimed to investigate the association of maternal glycemic control with the risk of gestational diabetes mellitus-related complications and small for gestational age in twin pregnancies complicated by gestational diabetes mellitus. STUDY DESIGN: This was a retrospective cohort study of all patients with a twin pregnancy complicated by gestational diabetes mellitus in a single tertiary center between 2011 and 2020, and a matched control group of patients with a twin pregnancy without gestational diabetes mellitus in a 1:3 ratio. The exposure was the level of glycemic control, described as the proportion of fasting, postprandial, and overall glucose values within target. Good glycemic control was defined as a proportion of values within target above the 50th percentile. The first coprimary outcome was a composite variable of neonatal morbidity, defined as at least 1 of the following: birthweight >90th centile for gestational age, hypoglycemia requiring treatment, jaundice requiring phototherapy, birth trauma, or admission to the neonatal intensive care unit at term. A second coprimary outcome was small for gestational age, defined as birthweight <10th centile or <3rd centile for gestational age. Associations between the level of glycemic control and the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence interval. RESULTS: A total of 105 patients with gestational diabetes mellitus in a twin pregnancy met the study criteria. The overall rate of the primary outcome was 32.4% (34/105), and the overall proportion of pregnancies with a small for gestational age newborn at birth was 43.8% (46/105). Good glycemic control was not associated with a reduction in the risk of composite neonatal morbidity when compared with suboptimal glycemic control (32.1% vs 32.7%; adjusted odds ratio, 2.06 [95% confidence interval, 0.77-5.49]). However, good glycemic control was associated with higher odds of small for gestational age compared with nongestational diabetes mellitus pregnancies, especially in the subgroup of diet-treated gestational diabetes mellitus (65.5% vs 34.0%, respectively; adjusted odds ratio, 4.17 [95% confidence interval, 1.74-10.01] for small for gestational age <10th centile; and 24.1% vs 7.0%, respectively; adjusted odds ratio, 3.97 [95% confidence interval, 1.42-11.10] for small for gestational age <3rd centile). In contrast, the rate of small for gestational age in gestational diabetes mellitus pregnancies with suboptimal control was not considerably different when compared with non-gestational diabetes mellitus pregnancies. In addition, in cases of diet-treated gestational diabetes mellitus, good glycemic control was associated with a left-shift of the distribution of birthweight centiles, whereas the distribution of birthweight centiles among gestational diabetes mellitus pregnancies with suboptimal control was similar to that of nongestational diabetes mellitus pregnancies. CONCLUSION: In patients with gestational diabetes mellitus in a twin pregnancy, good glycemic control is not associated with a reduction in the risk of gestational diabetes mellitus-related complications but may increase the risk of a small for gestational age newborn in the subgroup of patients with mild (diet-treated) gestational diabetes mellitus. These findings further question whether the gestational diabetes mellitus glycemic targets used in singleton pregnancies also apply to twin pregnancies and support the concern that applying the same diagnostic criteria and glycemic targets in twin pregnancies may result in overdiagnosis and overtreatment of gestational diabetes mellitus and potential neonatal harm.

Pre-phototherapy total serum bilirubin levels in extremely preterm infants.

BACKGROUND: Extremely preterm infants are prone to hyperbilirubinemia and its sequelae. Currently recommended thresholds for initiating phototherapy in these newborns are consensus-based (CB). METHODS: A multi-site retrospective cohort study of 642 infants born at 240/7 to 286/7 weeks' gestation, between January 2013 and June 2017, was conducted at three NICUs in Canada. Pre-phototherapy TSB percentile levels at 24 h of age were generated and contrasted with published CB thresholds. RESULTS: Among infants born 240/7 to 256/7 weeks' gestation, the differences between our TSB percentiles vs. the CB threshold of 85.0 µmol/L were 10.0 µmol/L (95% CI, 6.0-16.0) at the 75th percentile and 35.3 µmol/L (95% CI, 26.1-42.8) at the 95th percentile. Respectively, among infants born at 260/7 to 276/7 weeks, differences were 19.4 µmol/L (95% CI, 16.8-23.4) and 43.3 µmol/L (95% CI, 34.7-46.9). Born at 280/7 to 286/7 weeks' gestation, differences between our 75th and 95th TSB percentiles and the CB threshold of 103 µmol/L were 6.9 µmol/L (95% CI, 3.2-12.0) and 36.0 µmol/L (95% CI, 31.0-44.3), respectively. CONCLUSIONS: We provide statistically derived pre-phototherapy TSB levels that may clarify patterns of pre-phototherapy TSB levels in extremely preterm infants. IMPACT: We present statistically derived pre-phototherapy total serum bilirubin levels in a cohort of extremely preterm infants. Most of these preterm infants received phototherapy-some at below currently published thresholds. There are notable differences between our statistically derived pre-phototherapy TSB levels and currently published lower limit TSB thresholds for phototherapy. Our study results assist in the understanding of pre-phototherapy TSB levels in extremely preterm infants.

A framework for understanding how midwives perceive and provide care management for pregnancies complicated by gestational diabetes or hypertensive disorders of pregnancy.

BACKGROUND: Both gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are common, and each are associated with adverse maternal and perinatal outcomes. Midwives may be the first point of care when these conditions arise. This study evaluated the experiences of midwives when providing care to women and people with pregnancies complicated by GDM or HDP. METHODS: A mixed methods study was completed in Ontario, Canada, using a sequential, explanatory approach. A total of 144 online surveys were completed by midwives, followed by 20 semi-structured interviews that were audio recorded and transcribed verbatim. Survey data were analysed using descriptive statistics. Thematic analysis was used to generate codes from the interview data, which were mapped to the Theoretical Domains Framework (TDF), to elucidate factors that might influence management. RESULTS: Most of the midwives' clinical behaviours relating to GDM or HDP were in keeping with guidelines and regulatory standards set by existing provincial standards. Six theoretical domains from the TDF appeared to influence midwives'care pathway: "Internal influences" included knowledge, skills and beliefs about capabilities; while "external influences" included social/professional role and identity, environmental context, and social influences. Interprofessional collaboration emerged as a significant factor on both the internal and external levels of influence. CONCLUSIONS: We identified barriers and facilitators that may improve the experiences of midwives and clients when GDM or HDP newly arises in a pregnancy, necessitating further consultation or management by another health care provider.

Midwives perceptions of managing pregnancies complicated by obesity: A mixed methods study.

OBJECTIVE: The growing prevalence of obesity is a concern for midwives. In Canada, the absence of regulatory standards, varying protocols and consultant preferences shape clinical decision making for the midwife and may lead to inconsistent practice. Our aim was to understand the barriers, enablers, and knowledge gaps that influenced experiences of midwives in Ontario, Canada when providing care to clients impacted by obesity. METHODS: Mixed methods design using a sequential, explanatory approach. Surveys conducted with midwives were administered using an online platform, followed by semi-structured interviews to understand the perspectives elicited in the survey in greater detail. Interviews were audio recorded and transcribed verbatim. Survey data were analyzed using descriptive statistics, and thematic analysis was used for generating codes, categories and themes from the interview data. RESULTS: 144 midwives completed the survey and 20 participated in an interview. The participants described their clinical management when caring for those with obesity which included considerations regarding additional tests/investigations, consultation and transfer of care, and place of birth. Up to 93% of surveyed midwives believed that clients with obesity were appropriate for midwifery-led care however there was less certainty about suitability as BMI increased to higher ranges such as > 45). The care management was influenced by beliefs and attitudes, knowledge, and system-level factors. Midwives experienced barriers such as inconsistent practices and role confusion, and felt ill equipped to care for pregnancies affected by obesity due to unclear guidelines. CONCLUSIONS: Overall, midwives believe clients with obesity are suitable for midwifery-led care due to its individualized, non-judgmental approach to care. Additional training for midwives and other obstetric care providers would be beneficial to help overcome barriers in providing effective care to pregnancies affected by obesity.

Hour-Specific Total Serum Bilirubin Percentiles for Infants Born at 29-35 Weeks' Gestation.

INTRODUCTION: As preterm infants are susceptible to hyperbilirubinemia, they require frequent close monitoring. Prior to initiation of phototherapy, hour-specific total serum bilirubin (TSB) percentile cut-points are lacking in these infants, which led to the current study. METHODS: A multi-site retrospective cohort study of preterm infants born between January 2013 and June 2017 was completed at 3 NICUs in Ontario, Canada. A total of 2,549 infants born at 290/7-356/7 weeks' gestation contributed 6,143 pre-treatment TSB levels. Hour-specific TSB percentiles were generated using quantile regression, further described by degree of prematurity, and among those who subsequently received phototherapy. RESULTS: Among all infants, at birth, hour-specific pre-treatment, TSB percentiles were 36.1 µmol/L (95% confidence interval [CI]: 34.3-39.3) at the 40th, 52.3 µmol/L (49.4-55.1) at the 75th, and 79.5 µmol/L (72.1-89.6) at the 95th percentiles. The corresponding percentiles were 39.3 µmol/L (35.9-43.2), 55.4 µmol/L (52.1-60.2), and 87.1 µmol/L (CI 70.5-102.4) prior to initiating phototherapy and 24.4 µmol/L (20.4-28.8), 35.3 µmol/L (31.1-41.5), and 52.0 µmol/L (46.1-62.4) among those who did not receive phototherapy. Among infants born at 29-32 weeks, pre-treatment TSB percentiles were 53.9 µmol/L (49.4-61.0) and 95.5 µmol/L (77.5-105.0) at the 75th and 95th percentiles, with respective values of 48.7 µmol/L (43.0-52.3), and 74.1 µmol/L (64.8-83.2) for those born at 33-35 weeks' gestation. CONCLUSION: Hour-specific TSB percentiles, derived from a novel nomogram, may inform how bilirubin is described in preterm newborns. Further research of pre-treatment TSB levels is required before clinical consideration.

Transcutaneous versus Total Serum Bilirubin Measurements in Preterm Infants.

INTRODUCTION: Transcutaneous bilirubin (TcB) measurement offers a noninvasive approach for bilirubin screening; however, its accuracy in preterm infants is unclear. This study determined the agreement between TcB and total serum bilirubin (TSB) among preterm infants. METHODS: A multisite prospective cohort study was conducted at 3 NICUs in Ontario, Canada, September 2016 to June 2018. Among 296 preterm infants born at 240/7 to 356/7 weeks, 856 TcB levels were taken at the forehead, sternum, and before and after the initiation of phototherapy with TSB measurements. Bland-Altman plots and 95% limits of agreement (LOA) expressed agreement between TcB and TSB. RESULTS: The overall mean TcB-TSB difference was -24.5 µmol/L (95% LOA -103.3 to 54.3), 1.6 µmol/L (95% LOA -73.4 to 76.5) before phototherapy, and -31.1 µmol/L (95% LOA -105.5 to 43.4) after the initiation of phototherapy. The overall mean TcB-TSB difference was -15.2 µmol/L (95% LOA -86.8 to 56.3) at the forehead and -24.4 µmol/L (95% LOA -112.9 to 64.0) at the sternum. The mean TcB-TSB difference was -31.4 µmol/L (95% LOA -95.3 to 32.4) among infants born 24-28 weeks, -25.5 µmol/L (95% LOA -102.7 to 51.8) at 29-32 weeks, and -15.9 µmol/L (95% LOA -107.4 to 75.6) at 33-35 weeks. Measures did not differ by maternal ethnicity. CONCLUSION: Among preterm infants, TcB may offer a noninvasive, immediate approach to screening for hyperbilirubinemia with more careful use in preterm infants born at <33 weeks' gestation, as TcB approaches treatment thresholds. Its underestimation of TSB after the initiation of phototherapy warrants the use of TSB for clinical decision-making after the initiation of phototherapy.

Suboptimal maternal and cord plasma pyridoxal 5' phosphate concentrations are uncommon in a cohort of Canadian pregnant women and newborn infants.

Vitamin B6 is important in fetal development, but little is known of the vitamin B6 status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5' phosphate (PLP; an indicator of vitamin B6 status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B6 and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B6 were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CßS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood (p < .0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20 nmol/L, respectively. Ninety eight percent of the women with supplemental B6 intake of at least the recommended dietary allowance had PLP concentrations >20 nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B6 deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B6 supplement use.

Low Serum Vitamin B-12 Concentrations Are Prevalent in a Cohort of Pregnant Canadian Women.

BACKGROUND: Among Canadian women of reproductive age, 5% and 20% have serum vitamin B-12 concentrations indicative of deficiency (<148 pmol/L) and marginal status (148-220 pmol/L), respectively. Given the association between suboptimal vitamin B-12 and adverse pregnancy outcomes, an understanding of vitamin B-12 status during pregnancy, and factors that influence it, is required. OBJECTIVE: This prospective analysis from the PREFORM (PREnatal FOlic acid exposuRe on DNA Methylation in the newborn infant) study investigated 1) vitamin B-12 status in a cohort of Canadian pregnant women and their newborns, 2) the association of maternal dietary vitamin B-12 intake with maternal and cord blood concentrations of vitamin B-12 and its biomarkers, and 3) the association of fetal genetic polymorphisms with cord blood concentrations of vitamin B-12 and its biomarkers. METHODS: In pregnant Canadian women (n = 368; mean ± SD age: 32 ± 5 y), vitamin B-12 intakes were assessed in early (0-16 wk) and mid- to late (23-37 wk) pregnancy. Serum vitamin B-12 and plasma total homocysteine (tHcy) and methylmalonic acid (MMA) in maternal blood at 12-16 wk of pregnancy and at delivery (28-42 wk) and in cord blood were measured and compared by using regression analyses. The associations of 28 fetal genetic variants in vitamin B-12 metabolism and cord blood vitamin B-12, tHcy, and MMA concentrations were assessed by using regression analysis, with adjustment for multiple testing. RESULTS: A total of 17% and 38% of women had deficient and 35% and 43% had marginal serum vitamin B-12 concentrations at 12-16 wk of pregnancy and at delivery, respectively. Only 1.9-5.3% had elevated MMA (>271 nmol/L), and no women had elevated tHcy (>13 µmol/L). Maternal dietary vitamin B-12 intake during pregnancy was either weakly associated or not associated with maternal and cord blood vitamin B-12 (r(2) = 0.17-0.24, P < 0.0008), tHcy (P = NS) and MMA (r(2) = 0.05-0.11, P < 0.001). Fetal genetic polymorphisms were not associated with cord blood concentrations of vitamin B-12 and its biomarkers. CONCLUSIONS: Deficient and marginal serum vitamin B-12 concentrations are prevalent in Canadian pregnant women with the use of traditional cutoffs, despite supplement use. Given the growing interest among women to adhere to a vegetarian diet that may be lower in vitamin B-12, and vitamin B-12's importance in pregnancy, the functional ramifications of these observations need to be elucidated. This trial was registered at clinicaltrials.gov as NCT02244684.

High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood.

BACKGROUND: Mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. However, the effects of increased folic acid intakes during pregnancy on maternal and cord blood folate concentrations have not been well established. OBJECTIVES: In this prospective study, we determined maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA) in a cohort of pregnant Canadian women and their newborns and examined the effect of maternal intakes of folate and folic acid and fetal genetic variants in folate metabolism on folate status. DESIGN: Folate and folic acid intakes of 368 Canadian pregnant women were assessed in early (0-16 wk) and late (23-37 wk) pregnancy. Blood concentrations of folate and UMFA were measured with the use of immunoassays and liquid chromatography-mass spectrometry, respectively, in maternal samples in early pregnancy (12-16 wk), at delivery (28-42 wk), and in cord blood. Four fetal genetic variants of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were assessed for their association with cord blood concentrations of folate and UMFA. RESULTS: Geometric mean (95% CI) maternal red blood cell (RBC) folate concentrations were 2417 nmol/L (2362, 2472 nmol/L ) and 2793 nmol/L (2721, 2867 nmol/L ) in early pregnancy and at delivery, respectively. The mean (95% CI) cord RBC folate concentration was 2689 nmol/L (2614, 2765 nmol/L). UMFA was detectable in >90% of maternal and cord plasma samples. Although 3 fetal MTHFR and DHFR genetic variants had no effect, the fetal MTHFR 677TT genotype was associated with significantly lower cord serum (P = 0.03) and higher cord RBC (P = 0.02) folate concentrations than those of the wild type. CONCLUSIONS: Notwithstanding differences in assays, maternal and cord RBC folate and plasma UMFA concentrations were higher than previously reported values. Functional ramifications of high folate and UMFA concentrations in maternal and fetal circulation warrant additional investigation because an excess folate status may affect long-term health outcomes of the offspring. This study was registered at www.clinicaltrials.gov as NCT02244684.

Pregnant Canadian Women Achieve Recommended Intakes of One-Carbon Nutrients through Prenatal Supplementation but the Supplement Composition, Including Choline, Requires Reconsideration.

BACKGROUND: Folate, vitamin B-6, vitamin B-12, and choline are involved in one-carbon metabolism and play critical roles in pregnancy including prevention of birth defects and promotion of neurodevelopment. However, excessive intakes may adversely affect disease susceptibility in offspring. Intakes of these nutrients during pregnancy are not well characterized. OBJECTIVE: Our aim was to determine dietary and supplemental intakes and major dietary sources of one-carbon nutrients during pregnancy. METHODS: In pregnant women (n = 368) at ≤16 wk postconception, supplement use >30 d before pregnancy was assessed by maternal recall and supplement and dietary intakes in early (0-16 wk) and late pregnancy (23-37 wk) were assessed by food-frequency questionnaire. RESULTS: Preconception, 60.1% (95% CI: 55.8, 64.3) of women used B vitamin-containing supplements. This increased to 92.8% (95% CI: 89.6, 95.2) in early and 89.0% (95% CI: 85.0, 92.3) in late pregnancy. Median supplemental folic acid, vitamin B-12, and vitamin B-6 were 1000 µg/d, 2.6 µg/d, and 1.9 mg/d, respectively. Forty-one percent and 50% of women had dietary intakes of folate and vitamin B-6 less than the estimated average requirement (520 mg/d dietary folate equivalents and 1.6 mg/d, respectively). Eight-seven percent of women had choline intakes less than the Adequate Intake (450 mg/d). Dietary intakes did not change appreciably during pregnancy. Fruits and vegetables and fortified foods contributed ∼57% to total dietary folate intake. Fruits and vegetables contributed ∼32% to total dietary vitamin B-6 intake and dairy and egg products contributed ∼37% to total dietary vitamin B-12 intake. CONCLUSIONS: Vitamin supplements were an important source of one-carbon nutrients during pregnancy in our sample. Without supplements, many women would not have consumed quantities of folate and vitamin B-6 consistent with recommendations. Given the importance of choline in pregnancy, further research to consider inclusion in prenatal supplements is warranted. This trial was registered at clinicaltrials.gov as NCT02244684.

The effect of distant reiki on pain in women after elective Caesarean section: a double-blinded randomised controlled trial.

INTRODUCTION: Approximately 25% of all babies in North America are delivered via Caesarean section (C-section). Though a common surgical procedure, C-section recovery can be painful. Opioids, specifically codeine, are commonly used to ease pain; however, its active metabolite, morphine, passes into breast milk, and may produce unwanted side effects in neonates; therefore, alternatives to opioids are being sought. Reiki is an ancient Japanese form of healing where practitioners transfer healing energy through light touch and positive healing intention. Although 1.2 million Americans use reiki to reduce pain or depression, there is a lack of strong evidence supporting its effectiveness. A recent systematic review showed existing studies to be of poor methodological quality, with the common limitation of lack of blinding. To overcome this issue, the authors used distant reiki to assess its effectiveness in reducing pain following an elective C-section. METHODS: In this randomised, double-blinded study, women who underwent an elective C-section were allocated to either usual care (control, n=40) or three distant reiki sessions in addition to usual care (n=40). Pain was assessed using a visual analogue scale (VAS). The primary endpoint was the Area Under the VAS-Time Curve (AUC) for days 1-3. Secondary measures included: the proportion of women who required opioid medications and dose consumed, rate of healing and vital signs. RESULTS: AUC for pain was not significantly different in the distant reiki and control groups (mean ± SD; 212.1 ± 104.7 vs 223.1 ± 117.8; p=0.96). There were no significant differences in opioid consumption or rate of healing; however, the distant reiki group had a significantly lower heart rate (74.3 ± 8.1 bpm vs 79.8 ± 7.9 bpm, p=0.003) and blood pressure (106.4 ± 9.7 mmHg vs 111.9 ± 11.0 mmHg, p=0.02) post surgery. CONCLUSION: Distant reiki had no significant effect on pain following an elective C-section. Clinical Trial Registration Number ISRCTN79265996.