Assessment of Thoracic Abnormalities in Premature Infants

Background: There is a large incidence of congenital thoracic abnormalities that manifest as deformities and or defects of anterior chest walls. Thoracic abnormalities in preterm infants may also be associated with malpositioning in the incubator in the presence of respiratory disease and prolonged mechanical ventilation. Immaturity of respiratory and musculoskeletal system need to compromise biomechanical function of thorax. Thus, the purpose of the study is to access the thoracic alteration and the factors associated with its abnormalities in the infants born prematurely. Objective: Assess thoracic alteration in premature infants. Methods: This was an observational study with infants in first year of age, born prematurely with birth weight < 2000g. Exclusion criteria were: major congenital malformations as defined by the centers for disease contol and prevention, grade III/IV intraventricular hemorrhage or preventricular leucomalacia. Physical examinations were performed independently to assess shoulder elevation and thoracic alterations. Results: 34 infants born prematurely were included for the study according to the inclusion criteria from which 20 infants (58.8%) showed thoracic abnormalities and remaining 14 infants (41.1%) were without abnormalities. Conclusion: The prevalence of thoracic abnormalities was high in infants born prematurely, and was associated with pulmonary disease, and may also have compromised the growth rate of these infants during the first year of life.

Prevalence and Infant Mortality of Major Congenital Malformations Stratified by Birthweight

<b><i>Background:</i></b> Low birthweight and major congenital malformations (MCMs) are key causes of infant mortality. <b><i>Objectives:</i></b> The aim of this study was to explore the prevalence of MCMs in infants with low and very low birthweight and analyze the impact of MCMs and birthweight on infant mortality. <b><i>Methods:</i></b> We determined prevalence and infant mortality of 28 life-threatening MCMs in very-low-birthweight (&#x3c;1,500 g, VLBW), low-birthweight (1,500–2,499 g, LBW), or normal-birthweight (≥2,500 g, NBW) infants in a cohort of 2,727,002 infants born in Germany in 2006–2017, using de-identified administrative data of the largest statutory public health insurance system in Germany. <b><i>Results:</i></b> The rates of VLBW, LBW, and NBW infants studied were 1.3% (34,401), 4.0% (109,558), and 94.7% (2,583,043). MCMs affected 0.5% (13,563) infants, of whom &#x3e;75% (10,316) had severe congenital heart disease. The prevalence (per 10,000) of any/cardiac MCM was increased in VLBW (286/176) and LBW (244/143), as compared to NBW infants (38/32). Infant mortality rates were significantly higher in infants with an MCM, as opposed to infants without an MCM, in each birthweight group (VLBW 28.5% vs. 11.5%, LBW 16.7% vs. 0.9%, and NBW 8.6% vs. 0.1%). For most MCMs, observed survival rates in VLBW and LBW infants were lower than expected, as calculated from survival rates of VLBW or LBW infants without an MCM, and NBW infants with an MCM. <b><i>Conclusions:</i></b> Infants with an MCM are more often born with LBW or VLBW, as opposed to infants without an MCM. Many MCMs carry significant excess mortality when occurring in VLBW or LBW infants.

Genetics of diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a life-threatening malformation characterised by failure of diaphragmatic development with lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). The incidence is 1:2000 corresponding to 8% of all major congenital malformations. Morbidity and mortality in affected newborns are very high and at present, there is no precise prenatal or early postnatal prognostication parameter to predict clinical outcome in CDH patients. Most cases occur sporadically, however, genetic causes have long been discussed to explain a proportion of cases. These range from aneuploidy to complex chromosomal aberrations and specific mutations often causing a complex phenotype exhibiting multiple malformations along with CDH. This review summarises the genetic variations which have been observed in syndromic and isolated cases of congenital diaphragmatic hernia.

Dihydroergotamine and triptan use to treat migraine during pregnancy and the risk of adverse pregnancy outcomes

Migraine is prevalent during pregnancy. Antimigraine medications such as dihydroergotamine (DHE) and triptans have been associated with adverse pregnancy outcomes in individual studies but lack of consensus remains. We compared the risk of prematurity, low birth weight (LBW), major congenital malformations (MCM), and spontaneous abortions (SA) associated with gestational use of DHE or triptans. Three cohort and one nested-case–control analyses were conducted within the Quebec Pregnancy Cohort to assess the risk of prematurity, LBW, MCM, and SA. Exposure was defined dichotomously as use of DHE or triptan during pregnancy. Generalized estimation equations were built to quantify the associations, adjusting for potential confounders. 233,900 eligible pregnancies were included in the analyses on prematurity, LBW, and MCM; 29,104 cases of SA were identified. Seventy-eight subjects (0.03%) were exposed to DHE and 526 (0.22%) to triptans. Adjusting for potential confounders, DHE and triptans were associated with increased risks of prematurity, LBW, MCM, and SA but not all estimates were statistically significant. DHE was associated with the risk of prematurity (aRR: 4.12, 95% CI 1.21–13.99); triptans were associated with the risk of SA (aOR: 1.63, 95% CI 1.34–1.98). After considering maternal migraine, all antimigraine specific medications increased the risk of some adverse pregnancy outcomes, but estimates were unstable.

Use of metoclopramide in the first trimester and risk of major congenital malformations: A systematic review and meta-analysis

Background Nausea and vomiting of pregnancy affects up to 80% of pregnant women, it typically occurs during the first trimester which is the most sensitive time for environmental exposures given organogenesis. Metoclopramide is an antiemetic drug used widely during NVP, but the findings of studies evaluating its safety of use in pregnancy is inconsistent. Therefore, we conducted a systematic review and meta-analysis to assess whether metoclopramide use during first trimester of pregnancy is associated with the risk of major congenital malformations. Methods The systematic search using database included Pubmed, Embase, Web of science, and Cochrane library. Studies written in English, comprising with an exposed group and a control group, reporting major congenital malformation as an outcome were included. Results Six studies assessing a total number of 33374 metoclopramide-exposed and 373498 controls infants were included in this meta-analysis. No significant increase in the rate of major congenital malformation was detected following metoclopramide use during first trimester (OR, 1.14; 95% CI, 0.93–1.38). Conclusions Metoclopramide use during first trimester of pregnancy was not associated with the risk of major congenital malformations.

Chloroquine and Hydroxychloroquine Use During Pregnancy and the Risk of Adverse Pregnancy Outcomes Using Real-World Evidence

Introduction: Chloroquine (CQ) and hydroxychloroquine (HCQ) are currently used for the prevention/treatment of malaria, and treatment of systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Although present data do not show their efficacy to treat COVID-19, they have been used as potential treatments for COVID-19. Given that pregnant women are excluded from randomized controlled trials, and present evidence are inconsistent and inconclusive, we aimed to investigate the safety of CQ or HCQ use in a large pregnancy cohort using real-world evidence.Methods: Using Quebec Pregnancy Cohort, we identified women who delivered a singleton liveborn, 1998–2015, (n = 233,748). The exposure time window for analyses on prematurity and low birth weight (LBW) was the second/third trimesters; was any time during pregnancy; only first trimester exposure was considered for analyses on major congenital malformations (MCM). The risk of prematurity, LBW, and MCM (overall and organ-specific) were quantified using generalized estimation equations.Results: We identified 288 pregnancies (0.12%) exposed to CQ (183, 63.5%) or HCQ (105, 36.5%) that resulted in liveborn singletons; CQ/HCQ was used for RA (17.4%), SLE (16.3%) or malaria (0.7%). CQ/HCQ was used for 71.8 days on average [standard-deviation (SD) 70.5], at a dose of 204.3 mg/d (SD, 155.6). We did not observe any increased risk related to CQ/HCQ exposure for prematurity (adjusted odds ratio [aOR] 1.39, 95%CI 0.84–2.30), LBW (aOR 1.11, 95%CI 0.59–2.06), or MCM (aOR 1.01, 95%CI 0.67–1.52).Conclusion: in this large CQ/HCQ exposed pregnancy cohort, we saw no clear increased risk of prematurity, LBW, or MCM, although number of exposed cases remained low.

Risk of Major Congenital Malformations or Perinatal or Neonatal Death With Insulin Detemir Versus Other Basal Insulins in Pregnant Women With Preexisting Diabetes: The Real-World EVOLVE Study

<p>OBJECTIVE: To compare the risk of severe adverse pregnancy complications in women with pre-existing diabetes.</p> <p>RESEARCH DESIGN AND METHODS: Multinational, prospective cohort study to assess the prevalence of newborns free from major congenital malformations, perinatal or neonatal death (primary endpoint) following treatment with insulin detemir (detemir) vs other basal insulins.</p> <p>RESULTS: Of 1,457 women included, 727 received detemir and 730 received other basal insulins. The prevalence of newborns free from major congenital malformations, perinatal or neonatal death was similar between detemir (97.0%) and other basal insulins (95.5%) (crude risk difference 0.015 [95% CI −0.01,0.04]; adjusted risk difference −0.003 [95% CI −0.03,0.03]). The crude prevalence of ≥1 congenital malformation (major + minor) was 9.4% vs 12.6%, with a similar risk difference before (−0.032 [95% CI −0.064,0.000]) and after (−0.036 [95% CI –0.081,0.009]) adjustment for confounders. Crude data showed lower maternal HbA_1c during the first trimester (6.5% vs 6.7% [48 vs 50 mmol/mol]; estimated mean difference −0.181 [95% CI −0.300,−0.062]) and the second trimester (6.1% vs 6.3% [43 vs 45 mmol/mol]; −0.139 [95% CI −0.232,−0.046]), and a lower prevalence of major hypoglycemia (6.0% vs 9.0%; risk difference −0.030 [95% CI −0.058,−0.002]), pre-eclampsia (6.4% vs 10.0%; −0.036 [95% CI −0.064,−0.007]), and stillbirth (0.4% vs 1.8%; −0.013 [95% CI −0.024,−0.002],) with detemir compared to other basal insulins. However, differences were not significant post-adjustment.</p> <p>CONCLUSION: Insulin detemir was associated with a similar risk to other basal insulins of major congenital malformations, perinatal or neonatal death, hypoglycemia, pre-eclampsia and stillbirth. </p>