Pre-pregnancy Diabetes Mellitus Research Articles

The IRELAnD study—investigating the role of early low-dose aspirin in diabetes mellitus: a double-blinded, placebo-controlled, randomized trial

Although aspirin therapy is being increasingly advocated with the intention of risk modification for a wide range of pregnancy complications, women with prepregnancy diabetes mellitus are commonly excluded from clinical trials. The primary aim of this study was to examine the effect of aspirin therapy on a composite measure of adverse perinatal outcome in pregnancies complicated by pregestational diabetes mellitus. A double-blinded, placebo-controlled randomized trial was conducted at 6 university-affiliated perinatology centers. Women with type 1 diabetes mellitus or type 2 diabetes mellitus of at least 6 months' duration were randomly allocated to 150-mg daily aspirin or placebo from 11 to 14 weeks' gestation until 36 weeks. Established vascular complications of diabetes mellitus, including chronic hypertension or nephropathy, led to exclusion from the trial. The primary outcome was a composite measure of placental dysfunction (preeclampsia, fetal growth restriction, preterm birth <34 weeks' gestation, or perinatal mortality). The planned sample size was 566 participants to achieve a 35% reduction in the primary outcome, assuming 80% statistical power. Secondary end points included maternal and neonatal outcomes and determination of insulin requirements across gestation. Data were centrally managed using ClinInfo and analyzed using SAS 9.4. The 2 treatment groups were compared using t tests or chi-square tests, as required, and longitudinal data were compared using a repeated-measures analysis. From February 2020 to September 2022, 191 patients were deemed eligible, 134 of whom were enrolled (67 randomized to aspirin and 67 to placebo) with a retrospective power of 64%. A total of 101 (80%) women had type 1 diabetes mellitus and 25 (20%) had type 2 diabetes mellitus. Reaching the target sample size was limited by the impact of the COVID-19 pandemic. Baseline characteristics were similar between the aspirin and placebo groups. Treatment compliance was very high and similar between groups (97% for aspirin, 94% for placebo). The risk of the composite measure of placental dysfunction did not differ between groups (25% aspirin vs 21% placebo; P=.796). Women in the aspirin group had significantly lower insulin requirements throughout pregnancy compared with the placebo group. Insulin requirements in the aspirin group increased on average from 0.7 units/kg at baseline to 1.1 units/kg by 36 weeks' gestation (an average 83% within-patient increase), and increased from 0.7 units/kg to 1.3 units/kg (a 181% within-patient increase) in the placebo group, over the same gestational period (P=.002). Serial hemoglobin A1c levels were lower in the aspirin group than in the placebo group, although this trend did not reach statistical significance. In this multicenter, double-blinded, placebo-controlled randomized trial, aspirin did not reduce the risk of adverse perinatal outcome in pregnancies complicated by prepregnancy diabetes mellitus. Compared with the placebo group, aspirin-treated patients required significantly less insulin throughout pregnancy, indicating a beneficial effect of aspirin on glycemic control. Aspirin may exert a plausible placenta-mediated effect on pregestational diabetes mellitus that is not limited to its antithrombotic properties.

MTNR1B gene variations and high pre-pregnancy BMI increase gestational diabetes mellitus risk in Chinese women

AimTo investigate the association of melatonin receptor 1B (MTNR1B) gene variations and pre-pregnancy body mass index (BMI) with gestational diabetes mellitus (GDM). Materials and MethodIn this study, 1566 Chinese Han pregnant women were enrolled and multiple genetic models were used to evaluate the association between MTNR1B gene polymorphisms and the risk of GDM. The clinical value of pre-pregnancy BMI in predicting GDM was analyzed and evaluated using receiver operating characteristic (ROC) curves. Several methods of analysis were used to examine the impact of gene-gene and gene-BMI interactions on the incidence of GDM influence. ResultsFor the MTNR1B gene, rs1387153 (C > T), rs10830962 (C > G), rs4753426 (T > C), and rs10830963 (C > G) are all risk mutations associated with the susceptibility of GDM. The ROC curve analysis indicated that the BMI demonstrated an area under the curve (AUC) of 0.595. Alongside, the sensitivity and specificity stood at 0.676 and 0.474 respectively. The maximum Joden index was found to be 0.150, with a corresponding critical BMI value of 20.5691 kg/m2. Interaction analysis revealed that gene–gene and gene–BMI interactions had no significant effect on GDM occurrence. ConclusionMTNR1B genetic variations confers the risk to GDM in Chinese women. Furthermore, the high pre-pregnancy BMI (≥20.5691 kg/m2) significantly increases the risk of GDM in Chinese women.

Prepregnancy body mass index and adverse perinatal outcomes in the presence of other maternal risk factors

High prepregnancy body mass index is one of the most common risk factors for adverse perinatal events. This study aimed to assess whether the association between maternal body mass index and adverse perinatal outcome is modified by other concomitant maternal risk factors. This was a retrospective cohort study of all singleton live births and stillbirths in the United States from 2016 to 2017, using data from the National Center for Health Statistics. Logistic regression was used to estimate the adjusted odds ratios and 95% confidence intervals between prepregnancy body mass index and a composite outcome of stillbirth, neonatal death, and severe neonatal morbidity. Modification of this association by maternal age, nulliparity, chronic hypertension, and prepregnancy diabetes mellitus was assessed on both multiplicative and additive scales. The study population included 7,576,417 women with singleton pregnancy; 254,225 (3.5%) were underweight, 3,220,432 (43.9%) had normal body mass index, 1,918,480 (26.1%) were overweight, and 1,062,177 (14.4%), 516,693 (7.0%), and 365,357 (5.0%) had class I, II, and III obesity, respectively. Rates of the composite outcome increased with increasing body mass index above normal values, compared with women with normal body mass index. Nulliparity (289,776; 38.6%), chronic hypertension (135,328; 1.8%), and prepregnancy diabetes mellitus (67,744; 0.89%) modified the association between body mass index and the composite perinatal outcome on both the additive and multiplicative scales. Nulliparous (vs parous) women had a higher rate of increase in adverse outcomes with increasing body mass index. For example, in nulliparous women, class III obesity was associated with 1.8-fold higher odds compared with normal body mass index (adjusted odds ratio, 1.77; 95% confidence interval, 1.73-1.83), whereas in parous women, the adjusted odds ratio was 1.35 (95% confidence interval, 1.32-1.39). Women with chronic hypertension or prepregnancy diabetes mellitus had higher outcome rates overall; however, the dose-response relationship with increasing body mass index was absent. Although the composite outcome rates increased with maternal age, the risk curves were relatively similar across obesity classes in all maternal age groups. Overall, underweight women had 7% higher odds of the composite outcome, and this increased to 21% in parous women. Women with elevated prepregnancy body mass index are at increased risk of adverse perinatal outcomes, and the magnitude of these risks differs by concomitant risk factors, including prepregnancy diabetes mellitus, chronic hypertension, and nulliparity. In particular, in woman with chronic hypertension or prepregnancy diabetes mellitus, there is no impact of increasing body mass index on adverse perinatal outcomes. However, overall rates remain high, and prepregnancy prevention of hypertension and diabetes mellitus should be emphasized among all women irrespective of body mass index.

Associations Between Rurality, pre-pregnancy Health Status, and Macrosomia in American Indian/Alaska Native Populations.

To examine the relationships between pre-pregnancy diabetes mellitus (DM), gestational diabetes mellitus (GDM), pre-pregnancy body mass index (BMI) and county-level social determinants of health, with infant macrosomia within a sample of American Indian/Alaska Native (AI/AN) women receiving Indian Health Service (IHS) care. The sample included women-infant dyads representing 1,136 singleton births from fiscal year 2011 (10/1/2019-9/30/2011). Data stemmed from the IHS Improving Health Care Delivery Data Project. Multivariate generalized linear mixed models were fitted to assess the association of macrosomia with pre-pregnancy health status and social determinants of health. Nearly half of the women in the sample were under age 25 years (48.6%), and most had Medicaid health insurance coverage (76.7%). Of those with a pre-pregnancy BMI measure, 66.2% were overweight or obese. Although few women had pre-pregnancy DM (4.0%), GDM was present in 12.8% of women. Most women had a normal term delivery (85.4%). Overweight, obesity, pre-pregnancy DM, and county-level rurality were all significantly associated with higher odds of infant macrosomia.

Association between maternal prepregnancy diabetes mellitus and preconception folic acid supplement use by Hispanic ethnicity: Findings from Georgia, New York City, and Puerto Rico PRAMS 2016–2018

AbstractBackgroundMaternal ethnicity, prepregnancy diabetes, and preconception folic acid intake, are all associated with increased risk of neural tube defects in the United States. We assessed the association between prepregnancy diabetes and preconception folic acid use by Hispanic ethnicity.MethodsWe used population‐based, cross‐sectional survey data from New York City, Georgia and Puerto Rico's 2016–2018 Pregnancy Risk Assessment Monitoring System (PRAMS). Prepregnancy Type 1 or Type 2 diabetes was self‐reported. Adequate preconception folic acid intake was defined as intake of a multivitamin, a prenatal vitamin, or a folic acid vitamin 4–7 times/week during the month before pregnancy. Multivariable logistic regression was used to calculate adjusted prevalence odds ratio (aPORs) and 95% confidence intervals (CI), stratified by Hispanic ethnicity.ResultsPrepregnancy diabetes was reported by 2.9% of Hispanic and 3.6% of non‐Hispanic participants. Adequate preconception folic acid use was reported by 25.9% and 39.9% of Hispanics and non‐Hispanics, respectively. There was an inverse association between prepregnancy diabetes and preconception folic acid use among Hispanics (aPOR = 0.75; 95% CI = 0.31, 1.81), while the association was positive among non‐Hispanics (aPOR = 1.26; 95% CI = 0.70, 2.26); however, the 95% confidence intervals for both groups contained the null value.ConclusionsThe association between prepregnancy diabetes and folic acid intake varied by Hispanic ethnicity. Our hypothesis that reproductive‐aged women with prepregnancy diabetes may receive timely diabetic care, including health counseling to take preconception folic acid, was not supported by our study data. Future studies should examine the association in additional PRAMS sites. Preconception health screening, and folic acid intake among Hispanics, should be strengthened.

Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study

STUDY QUESTIONIs the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception?SUMMARY ANSWERInfertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment.WHAT IS KNOWN ALREADYInfertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear.STUDY DESIGN, SIZE, DURATIONThis population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006–2014. Outcomes were assessed up to June 2020.PARTICIPANTS/MATERIALS, SETTING, METHODSLinked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at ≥24 weeks gestation between 2006 and 2014, and who were alive at age 4 years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4 years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm <37 weeks) and neonatal adverse morbidity (absent or present).MAIN RESULTS AND THE ROLE OF CHANCEThe study included 925 488 children born to 663 144 mothers, of whom 805 748 (87%) were from an unassisted conception, 94 206 (10.2%) followed infertility but no fertility treatment, 11 777 (1.3%) followed OI/IUI and 13 757 (1.5%) followed IVF/ICSI. Starting at age 4 years, children were followed for a median (interquartile range) of 6 (4–8) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI/IUI group and 6.3% in the IVF/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI/IUI group and 12.2 in the IVF/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16–1.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01–1.17) in the OI/IUI group and 1.12 (95% CI 1.04–1.20) in the IVF/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males.LIMITATIONS, REASONS FOR CAUTIONSome mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding.WIDER IMPLICATIONS OF THE FINDINGSInfertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study.STUDY FUNDING/COMPETING INTEREST(s)This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest.TRIAL REGISTRATION NUMBERN/A.

Association of the Cerebro-Placental Ratio With Adverse Outcomes in Pregnancies Affected by Gestational Diabetes Mellitus.

Cerebro-placental ratio (CPR) is a doppler tool contributes to clinical decision-making in pregnancies affected by small for gestational age weight (SGA). Pregnancies affected by gestational diabetes mellitus (GDM) tend to have higher newborn weight, but greater risk of adverse perinatal outcomes. We hypothesized that in GDM-complicated-pregnancies CPR will be associated with adverse perinatal outcomes even in the absence of SGA. This prospective single-center cohort study included non-anomalous singleton pregnancies in women with GDM. Those with pre-pregnancy diabetes mellitus, hypertensive disorder or suspected SGA were excluded. Routine fetal sonographic assessment included CPR-defined as middle cerebral artery pulsatilty index/umbilical artery pulsatilty index. Masked CPR measurement closest to birth was used, classified as >10th (normal) or ≤10th centile (low). Primary outcome was a composite, consisting of stillbirth, Caesarean birth due to abnormal fetal heart rate pattern, 5-minute Apgar <7, cord arterial pH < 7.0, hypoxic ischemic encephalopathy, or NICU admission >24hours. Of 281 participants, 24 (8.5%) had low CPR, at a mean gestational age of 36.3 weeks (IQR 34.0-37.4). Birthweight percentile was significantly lower among the low CPR group (35th [IQR 16-31] versus 60th [IQR 31-82]; P=.002). There was no statistically difference in the primary composite outcome between the groups (8.3% versus 7.0%, P=.68). Low CPR was significantly associated with a higher risk of neonatal hypoglycemia (adjusted odds ratio 3.2, 95% CI 1.2-8.3). In pregnancies affected by GDM, CPR ≤10th percentile was not associated with adverse perinatal outcome but was associated with neonatal hypoglycemia.

Associations Among Maternal Metabolic Conditions, Cord Serum Leptin Levels, and Autistic Symptoms in Children.

IntroductionAccumulating evidence has shown that maternal metabolic conditions, such as pre-pregnancy overweight, diabetes mellitus, and hypertensive disorders of pregnancy (HDP) are potential risk factors of autism spectrum disorder (ASD). However, it remains unclear how these maternal conditions lead to neurodevelopmental outcomes in the offspring, including autistic symptoms. Leptin, an adipokine that has pro-inflammatory effects and affects fetal neurodevelopment, is a candidate mediator of the association between maternal metabolic factors and an increased risk of ASD. However, whether prenatal exposure to leptin mediates the association between maternal metabolic conditions and autistic symptoms in children has not been investigated yet.MethodsThis study investigated the associations between mothers' metabolic conditions (pre-pregnancy overweight, diabetes mellitus during or before pregnancy, and HDP), leptin concentrations in umbilical cord serum, and autistic symptoms among 762 children from an ongoing cohort study, using generalized structural equation modeling. We used the Social Responsive Scale, Second Edition (SRS-2) at 8–9 years old to calculate total T-scores. Additionally, we used the T-scores for two subdomains: Social Communication and Interaction (SCI) and Restricted Interests and Repetitive Behavior (RRB).ResultsUmbilical cord leptin levels were associated with pre-pregnancy overweight [coefficient = 1.297, 95% confidence interval (CI) 1.081–1.556, p = 0.005] and diabetes mellitus (coefficient = 1.574, 95% CI 1.206–2.055, p = 0.001). Furthermore, leptin levels were significantly associated with SRS-2 total T-scores (coefficient = 1.002, 95% CI 1.000–1.004, p = 0.023), SCI scores (coefficient = 1.002, 95% CI 1.000–1.004, p = 0.020), and RRB scores (coefficient = 1.001, 95% CI 1.000–1.003, p = 0.044) in children. Associations between maternal metabolic factors and autistic symptoms were not significant.DiscussionThe present study uncovered an association between cord leptin levels and autistic symptoms in children, while maternal metabolic conditions did not have an evident direct influence on the outcome. These results imply that prenatal pro-inflammatory environments affected by maternal metabolic conditions may contribute to the development of autistic symptoms in children. The findings warrant further investigation into the role of leptin in the development of autistic symptoms.

Changed definition of disease and broader screening criteria had little impact on prevalence of gestational diabetes mellitus.

There are major controversies in screening for gestational diabetes mellitus (GDM). The present study evaluates the impact of the 2017 revised guidelines for GDM screening and a changed definition of GDM in Norway. We used a case-series design and included women with no pre-pregnancy diabetes mellitus, who gave birth after gestational week 29 to a singleton fetus at the University Hospital of North Norway, Tromsø, or at a local maternity ward in Troms county, during the first 6months of 2013 (before group, n=676) and 2018 (after group, n=673). Data were collected from antenatal records, maternal health information sheets, and electronic medical records (Partus). We assessed the screening criteria age, parity, pre-pregnancy BMI, and ethnicity. Primary outcomes were change in size of the population eligible for GDM screening, screening adherence, and prevalence of GDM, and follow up of GDM (treatment and obstetric risk assessment at gestational week 36). Statistical analyses were done using IBM SPSS with chi-squared test. A p value less than 0.05 was considered statistically significant. The proportion of women eligible for GDM screening increased from 46.4% in the before group to 67.6% in the after group (+45%) (p<0.01). However, screening adherence among eligible women was only 28.3% and 49.2% in the before and after groups, respectively (p<0.01). Among screened women, 16.9% (15/89) and 10.7% (24/224), respectively, were diagnosed with GDM, resulting in an overall estimated prevalence of 2.2% (15/676) and 3.6% (24/673). Among women diagnosed with GDM, 13.3% received no follow up in 2013 and this proportion was 20.8% in 2018. The remaining women underwent obstetric risk assessment at gestational week 36 as advised in the guidelines. The introduction of broader screening criteria and a more liberal case definition increased the population eligible for GDM screening by 45%. The higher proportion of women screened resulted in an insignificant higher prevalence of GDM. Screening adherence was poor in both study groups. Stakeholders for obstetric care need to consolidate quality measures and revisit the screening algorithm.

Maternal and neonatal outcomes in mothers with diabetes mellitus in Qatari population

BackgroundDiabetes Mellitus (DM) is a major cause of maternal, fetal, and neonatal morbidities. Our objective was to estimate the effect of both pre-pregnancy and gestational DM on the growth parameters of newborns in the Qatari population.MethodsIn this population-based cohort study, we compared the data of neonates born to Qatari women with both pre-pregnancy and gestational diabetes mellitus in 2017 with neonates of healthy non-diabetic Qatari women.ResultsOut of a total of 17020 live births in 2017, 5195 newborns were born to Qatari women. Of these, 1260 were born to women with GDM, 152 were born to women with pre-pregnancy DM and 3783 neonates were born to healthy non-diabetic (control) women. The prevalence of GDM in the Qatari population in 2017 was 24.25%. HbA1C% before delivery was significantly higher in women with pre-pregnancy DM (mean 6.19 ± 1.15) compared to those with GDM (mean 5.28 ± 0.43) (P <0.0001). The mean birth weight in grams was 3066.01 ± 603.42 in the control group compared to 3156.73 ± 577.88 in infants born to women with GDM and 3048.78 ± 677.98 in infants born to women with pre-pregnancy DM (P <0.0001). There was no statistically significant difference regarding the mean length (P= 0.080), head circumference (P= 0.514), and rate of major congenital malformations (P= 0.211). Macrosomia (Birth weight > 4000 gm) was observed in 2.7% of the control group compared to 4.8% in infants born to women with GDM, and 4.6% in infants born to women with pre-pregnancy DM (P= 0.001). Multivariate logistic regression analysis demonstrated that higher maternal age (adjusted OR 2.21, 95% CI 1.93, 2.52, P<0.0001), obesity before pregnancy (adjusted OR 1.71, 95% CI 1.30, 2.23, P<0.0001), type of delivery C-section (adjusted OR 1.25, 95% CI 1.09, 1.44, P=0.002), and body weight to gestational age LGA (adjusted OR 2.30, 95% CI 1.64, 2.34, P<0.0001) were significantly associated with increased risk of GDM.ConclusionDespite the multi-disciplinary antenatal diabetic care management, there is still an increased birth weight and an increased prevalence of macrosomia among the infants of diabetic mothers. More efforts should be addressed to improve the known modifiable factors such as women's adherence to the diabetic control program. Furthermore, pre-pregnancy BMI was found to be significantly associated with gestational DM, and this is a factor that can be addressed during pre-conceptional counseling.

COVID-19 vaccination during pregnancy: coverage and safety

BackgroundConcerns have been raised regarding a potential surge of COVID-19 in pregnancy, secondary to the rising numbers of COVID-19 in the community, easing of societal restrictions, and vaccine hesitancy. Although COVID-19 vaccination is now offered to all pregnant women in the United Kingdom; limited data exist on its uptake and safety.ObjectiveThis study aimed to investigate the uptake and safety of COVID-19 vaccination among pregnant women.Study DesignThis was a cohort study of pregnant women who gave birth at St George’s University Hospitals National Health Service Foundation Trust, London, United Kingdom, between March 1, 2020, and July 4, 2021. The primary outcome was uptake of COVID-19 vaccination and its determinants. The secondary outcomes were perinatal safety outcomes. Data were collected on COVID-19 vaccination uptake, vaccination type, gestational age at vaccination, and maternal characteristics, including age, parity, ethnicity, index of multiple deprivation score, and comorbidities. Further data were collected on perinatal outcomes, including stillbirth (fetal death at ≥24 weeks’ gestation), preterm birth, fetal and congenital abnormalities, and intrapartum complications. Pregnancy and neonatal outcomes of women who received the vaccine were compared with that of a matched cohort of women with balanced propensity scores. Effect magnitudes of vaccination on perinatal outcomes were reported as mean differences or odds ratios with 95% confidence intervals. Factors associated with antenatal vaccination were assessed with logistic regression analysis.ResultsData were available for 1328 pregnant women of whom 140 received at least 1 dose of the COVID-19 vaccine before giving birth and 1188 women who did not; 85.7% of those vaccinated received their vaccine in the third trimester of pregnancy and 14.3% in the second trimester of pregnancy. Of those vaccinated, 127 (90.7%) received a messenger RNA vaccine and 13 (9.3%) a viral vector vaccine. There was evidence of reduced vaccine uptake in younger women (P=.001), women with high levels of deprivation (ie, fifth quintile of the index of multiple deprivation; P=.008), and women of Afro-Caribbean or Asian ethnicity compared with women of White ethnicity (P<.001). Women with prepregnancy diabetes mellitus had increased vaccine uptake (P=.008). In the multivariable model the fifth deprivation quintile (most deprived) (adjusted odds ratio, 0.10; 95% confidence interval, 0.02–0.10; P=.003) and Afro-Caribbean ethnicity (adjusted odds ratio, 0.27; 95% confidence interval, 0.06–0.85; P=.044) were significantly associated with lower antenatal vaccine uptake, whereas prepregnancy diabetes mellitus was significantly associated with higher antenatal vaccine uptake (adjusted odds ratio, 10.5; 95% confidence interval, 1.74–83.2; P=.014). In a propensity score–matched cohort, the rates of adverse pregnancy outcomes of 133 women who received at least 1 dose of the COVID-19 vaccine in pregnancy were similar to that of unvaccinated pregnant women (P>.05 for all): stillbirth (0.0% vs 0.2%), fetal abnormalities (2.2% vs 2.5%), postpartum hemorrhage (9.8% vs 9.0%), cesarean delivery (30.8% vs 34.1%), small for gestational age (12.0% vs 12.8%), maternal high-dependency unit or intensive care admission (6.0% vs 4.0%), or neonatal intensive care unit admission (5.3% vs 5.0%). Intrapartum pyrexia (3.7% vs 1.0%; P=.046) was significantly increased but the borderline statistical significance was lost after excluding women with antenatal COVID-19 infection (P=.079). Mixed-effects Cox regression showed that vaccination was not significantly associated with birth at <40 weeks’ gestation (hazard ratio, 0.93; 95% confidence interval, 0.71–1.23; P=.624).ConclusionOf pregnant women eligible for COVID-19 vaccination, less than one-third accepted COVID-19 vaccination during pregnancy, and they experienced similar pregnancy outcomes with unvaccinated pregnant women. There was lower uptake among younger women, non-White ethnicity, and lower socioeconomic background. This study has contributed to the body of evidence that having COVID-19 vaccination in pregnancy does not alter perinatal outcomes. Clear communication to improve awareness among pregnant women and healthcare professionals on vaccine safety is needed, alongside strategies to address vaccine hesitancy. These strategies include postvaccination surveillance to gather further data on pregnancy outcomes, particularly after first-trimester vaccination, and long-term infant follow-up.

Association of pre- and early-pregnancy factors with the risk for gestational diabetes mellitus in a large Chinese population

Gestational diabetes mellitus (GDM) has aroused wide public concern, as it affects approximately 1.8–25.1% of pregnancies worldwide. This study aimed to examine the association of pre-pregnancy demographic parameters and early-pregnancy laboratory biomarkers with later GDM risk, and further to establish a nomogram prediction model. This study is based on the big obstetric data from 10 “AAA” hospitals in Xiamen. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria. Data are analyzed using Stata (v14.1) and R (v3.5.2). Total 187,432 gestational women free of pre-pregnancy diabetes mellitus were eligible for analysis, including 49,611 women with GDM and 137,821 women without GDM. Irrespective of confounding adjustment, eight independent factors were consistently and significantly associated with GDM, including pre-pregnancy body mass index (BMI), pre-pregnancy intake of folic acid, white cell count, platelet count, alanine transaminase, albumin, direct bilirubin, and creatinine (p < 0.001). Notably, per 3 kg/m2 increment in pre-pregnancy BMI was associated with 22% increased risk [adjusted odds ratio (OR) 1.22, 95% confidence interval (CI) 1.21–1.24, p < 0.001], and pre-pregnancy intake of folic acid can reduce GDM risk by 27% (adjusted OR 0.73, 95% CI 0.69–0.79, p < 0.001). The eight significant factors exhibited decent prediction performance as reflected by calibration and discrimination statistics and decision curve analysis. To enhance clinical application, a nomogram model was established by incorporating age and above eight factors, and importantly this model had a prediction accuracy of 87%. Taken together, eight independent pre-/early-pregnancy predictors were identified in significant association with later GDM risk, and importantly a nomogram modeling these predictors has over 85% accuracy in early detecting pregnant women who will progress to GDM later.

The effects of Helicobacter pylori infection on pregnancy-related diseases and fetal development in diabetes in pregnancy

BackgroundThis study aimed to determine the association of Helicobacter pylori (H. pylori) infection with pregnancy-related diseases and fetal development in women with diabetes in pregnancy (DIP).MethodsAll the participants were recruited before 16 weeks of gestation. According to their medical history and the results of a 75-g oral glucose tolerance test at the 24th week of pregnancy, the participants were divided into a normal control group (NC group), a gestational diabetes mellitus group (GDM group), and a pre-pregnancy diabetes mellitus group (PGDM group). According to the results of an H. pylori serum antibody detection test, each group was further divided into two subgroups: an H. pylori positive subgroup (HP+ subgroup) and an H. pylori negative group (HP- subgroup). The incidences of pregnancy-related diseases, the fetal developmental status, and the newborn status were compared among the groups.ResultsThis study recruited 356 pregnant women. The infection rates of type I H. pylori were significantly higher in the GDM group and the PGDM group than in the NC group (χ2=6.949, P=0.031). With the exception of the NC-HP+ subgroup, there were higher incidences of pregnancy-related diseases in the HP+ subgroups than in the HP− subgroups (P<0.05). Furthermore, the incidences of pregnancy-induced hypertension (PIH), preeclampsia, and premature delivery were significantly higher in the GDM-HP+ subgroup and the PGDM-HP+ subgroup than in the NC-HP+ subgroup (P<0.05). At the end of pregnancy, all 3 HP− subgroups showed better fetal development than the HP+ subgroups (P<0.05), and the NC-HP+ subgroup showed better fetal development than the GDM-HP+ and PGDM-HP+ subgroups (P<0.05). Meanwhile, the PGDM-HP+ subgroup showed poor fetal development, even in the 2nd trimester of pregnancy.ConclusionsH. pylori infection is extremely common in DIP. For women with DIP, infection with H. pylori can increase the risks of pregnancy-related diseases and poor fetal development. H. pylori screening and eradication therapy before pregnancy may aid in preventing pregnancy-related diseases and improve fetal development.

Neurodevelopmental outcomes of infants of diabetic mothers.

With the increase of the incidence of pre-pregnancy diabetes mellitus and gestational diabetes mellitus, the number of infants of diabetic mothers (IDMs) are increasing year by year. IDMs may be associated with poor perinatal outcomes and may have a negative impact on neurodevelopment, but there are relatively few studies on the neurodevelopmental outcomes of IDMs. This article reviews the relevant literature and summarizes the neurodevelopmental outcomes of IDMs from the aspects of sensory and perception, motor, language, intellectual development, neuropsychiatric disorders, neurological examination and drug effect, so as to provide reference for clinical work. Citation.

Association of Maternal Prepregnancy Diabetes and Gestational Diabetes Mellitus With Congenital Anomalies of the Newborn.

To examine the association of maternal prepregnancy diabetes, gestational diabetes mellitus (GDM), and 12 subtypes of congenital anomalies of the newborn. We included 29,211,974 live births with maternal age ranging from 18 to 49 years old documented in the National Vital Statistics System in the U.S. from 2011 to 2018. Information on prepregnancy diabetes, GDM, and congenital anomalies was retrieved from birth certificates. Log-binomial regression was used to estimate risk ratios (RRs) and 95% CIs for congenital anomalies overall and by subtypes. Of the 29,211,974 live births, there were 90,061 infants who had congenital anomalies identified at birth. The adjusted RRs of congenital anomalies at birth were 2.44 (95% CI 2.33-2.55) for prepregnancy diabetes and 1.28 (95% CI 1.24-1.31) for GDM. The associations were generally consistent across subgroups by maternal age, race/ethnicity, prepregnancy obesity status, and infant sex. For specific subtypes of congenital anomalies, maternal prepregnancy diabetes or GDM was associated with an increased risk of most subtypes. For example, the adjusted RRs of cyanotic congenital heart disease were 4.61 (95% CI 4.28-4.96) for prepregnancy diabetes and 1.50 (95% CI 1.43-1.58) for GDM; the adjusted RRs of hypospadias were 1.88 (95% CI 1.67-2.12) for prepregnancy diabetes and 1.29 (95% CI 1.21-1.36) for GDM. Prepregnancy diabetes and, to a lesser extent, GDM were associated with several subtypes of congenital anomalies of the newborn. These findings suggest potential benefits of preconception counseling in women with preexisting diabetes or at risk for GDM for the prevention of congenital anomalies.

Risk of severe maternal morbidity or death in relation to elevated hemoglobin A1c preconception, and in early pregnancy: Apopulation-based cohort study.

BackgroundThe relation between prepregnancy average glucose concentration and a woman’s risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM).Methods and findingsA population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16–50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks’ gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14–1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13–1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07–1.14; p < 0.001) and without (1.15, 95% CI 1.02–1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11–1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04–1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06–1.62; p = 0.01) in those with a preconception A1c of 5.8%–6.4%, and 2.84 (95% CI 2.31–3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76–6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women.ConclusionsOur findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.

BRAzil magnesium (BRAMAG) trial: a double-masked randomized clinical trial of oral magnesium supplementation in pregnancy

BackgroundThere is conflicting evidence about the role of oral magnesium supplementation in the prevention of preterm birth and related adverse outcomes. The objective of this study was to compare magnesium citrate with placebo in the prevention of adverse perinatal and maternal outcomes among women at higher risk.MethodsThis multicenter, double-masked, placebo-controlled randomized superiority clinical trial compared oral magnesium citrate 300 mg to matched placebo, from 12 to 20 weeks’ gestation until delivery. This trial was completed in three centers in northeastern Brazil. Eligible women were those with a singleton pregnancy and ≥ 1 risk factor, such as prior preterm birth or preeclampsia, or current chronic hypertension or pre-pregnancy diabetes mellitus, age > 35 years or elevated body mass index. The primary perinatal composite outcome comprised preterm birth < 37 weeks’ gestation, stillbirth > 20 weeks, neonatal death or NICU admission < 28 days after birth, or small for gestational age birthweight < 3rd percentile. The co-primary maternal composite outcome comprised preeclampsia or eclampsia < 37 weeks, severe gestational hypertension < 37 weeks, placental abruption, or maternal stroke or death during pregnancy or ≤ 7 days after delivery.ResultsAnalyses comprised 407 women who received magnesium citrate and 422 who received placebo. The perinatal composite outcome occurred among 75 (18.4%) in the magnesium arm and 76 (18.0%) in the placebo group – an adjusted odds ratio (aOR) of 1.10 (95% CI 0.72–1.68). The maternal composite outcome occurred among 49 (12.0%) women in the magnesium arm and 41 women (9.7%) in the placebo group – an aOR of 1.29 (95% CI 0.83–2.00).ConclusionsOral magnesium citrate supplementation did not appear to reduce adverse perinatal or maternal outcomes in high-risk singleton pregnancies.Trial registrationClinicalTrials.gov NCT02032186, registered January 9, 2014.

Impact of diabetes, obesity and hypertension on preterm birth: Population-based study.

ObjectiveTo determine the impact of pre-pregnancy diabetes mellitus (D), obesity (O) and chronic hypertension (H) on preterm birth (PTB).MethodsRetrospective population-based cohort study in Ontario, Canada between 2012–2016. Women who had a singleton livebirth or stillbirth at > 20 weeks gestation were included in the cohort. Exposures of interest were D, O and H, individually, and in various combinations. The primary outcome was PTB at 241/7 to 366/7 weeks. PTB was further analyzed by spontaneous or provider-initiated, early (< 34 weeks) or late (34–37 weeks), and the co-presence of preeclampsia, large for gestational age (LGA), and small for gestational age (SGA). Multivariable Poisson regression models with robust error variance were used to generate relative risks (RR), further adjusted for maternal age and parity (aRR). Population attributable fractions (PAF) were calculated for each of the outcomes by exposure state.Results506,483 women were eligible for analysis. 30,139 pregnancies (6.0%) were complicated by PTB < 37 weeks, of which 7375 (24.5%) had D or O or H. Relative to women without D or O or H, the aRR for PTB < 37 weeks was higher for D (3.51; 95% CI 3.26–3.78) and H (3.81; 95% CI 3.55–4.10) than O (1.14; 95% CI 1.10–1.17). The combined state of DH was associated with a significantly higher aRR of PTB < 37 weeks (6.34; 95% CI 5.14–7.80) and < 34 weeks (aRR 10.33, 95% CI 6.96–15.33) than D alone. The risk of provider initiated PTB was generally higher than that for spontaneous PTB. Pre-pregnancy hypertension was associated with the highest risk for PTB with preeclampsia (aRR 45.42, 95% CI 39.69–51.99) and PTB with SGA (aRR 9.78, 95% CI 7.81–12.26) while pre-pregnancy diabetes was associated with increased risk for PTB with LGA (aRR 28.85, 95% CI 24.65–33.76).ConclusionCombinations of DOH significantly magnify the risk of PTB, especially provider initiated PTB, and PTB with altered fetal growth or preeclampsia.

Timing of delivery in women with pre-pregnancy diabetes mellitus: a population-based study

ObjectivesControversy exists about the timing of delivery of women with pre-pregnancy type 1 and 2 diabetes mellitus (PDM). This study aims to compare maternal and neonatal outcomes after induction of...

Maternal clinical profile and immediate neonatal outcome in term large for gestational age neonates

Background: The objective of the study was to know the maternal clinical profile and short term outcome of term large-for-gestational-age (LGA) neonates.Methods: The study was a prospective observational study conducted in the tertiary neonatal unit, Odisha, during the study period February to November 2018. All inborn term neonates with birth weight above 90th percentile for gestational age excluding neonates with major congenital anomalies were included. Maternal clinical profile data from the antenatal records, neonatal demographic profile and co-morbidities over time were recorded using a checklist. The analysis of data was done using SPSS 21.0. Univariate summary statistics and bivariate Fischer’s exact test were used to analyse the data.Results: The prevalence of delivery of LGA and macrosomic neonate in our institution was 2.5%, and 1.1% respectively. Ninety one percent of LGA neonates were born before 39weeks and 80% babies delivered by cesarean section. Majority 39 (86.7%) of LGA babies were born to non-diabetic mother, four (8.9%) neonates born to GDM mother, two (4.4%) were born to mother with pre pregnancy diabetes mellitus. Sixteen (35.5%) neonates were admitted to NICU for different comorbidities like neonatal jaundice (37.8%), polycythemia (24.4%), transient tachypnea of new-born (20%), hypoglycemia (15.6%), hypocalcaemia (15.6%), and seizure (4.4%). The comorbidities like hypoglycaemia, hypocalcemia, respiratory distress were more in LGA babies with diabetic mother compared to non-diabetic mother.Conclusions: About nine in ten LGA neonates were born to non-diabetic mothers, however, LGA infants of diabetic mothers are at higher risk of metabolic complications like hypoglycemia, hypocalcemia compared to non-diabetic mother.