trimethoprim--sulfamethoxazole-drug-combination and Fetal-Growth-Retardation

Tricho-hepato-enteric syndrome (THES) is a rare disorder caused by mutations in the TTC37 or SKIV2L genes and characterized by chronic diarrhea, liver disease, hair abnormalities, and high mortality in early childhood due to severe infection or liver cirrhosis.. The patient is the second child of three siblings born to non-consanguineous healthy Japanese parents. She had intrauterine growth retardation and was delivered at 33 weeks of gestation due to placental abruption. She presented with watery diarrhea, elevated levels of liver enzymes, multiple episodes of recurrent bacterial infection, and mild mental retardation. She had facial dysmorphism, including prominent forehead and hypertelorism, and had woolly hair without trichorrhexis nodosa.. Clinical features led to consideration of THES. Novel compound heterozygous nonsense mutations, c.1420G>T (p.Q474*) and c.3262G>T (p.E1088*), in the SKIV2L gene were identified in the patient, and decreased levels of SKIV2L protein expression were revealed by flow cytometry and confirmed by western blot analysis using patient peripheral blood mononuclear cells (PBMCs).. Total parenteral nutrition was required from day 30 to day 100. Trimethoprim-sulfamethoxazole prophylaxis was started at the age of 7 years after multiple episodes of bacterial pneumonia and otitis media.. Chronic diarrhea persisted for more than 10 years, but the symptoms gradually improved with age. At the age of 13 years, she started a normal diet in combination with oral nutritional supplementation and her height and weight were just below the 3rd percentile for healthy individuals. She developed secondary sex characteristics, and menarche occurred at the age of 12 years. Facial dysmorphism, including prominent forehead and hypertelorism, and woolly hair without trichorrhexis nodosa became noticeable as she matured.. Physicians must be aware of THES when they encounter a patient with infantile diarrhea, hair abnormalities, immune deficiency, mental retardation, and liver disease. Moreover, flow cytometric detection of SKIV2L protein in PBMCs may facilitate early diagnosis.

Topics: Blotting, Western; Codon, Nonsense; Diagnosis, Differential; Diarrhea, Infantile; DNA Helicases; Facies; Female; Fetal Growth Retardation; Flow Cytometry; Hair Diseases; Humans; Infant, Newborn; Japan; Parenteral Nutrition; Trimethoprim, Sulfamethoxazole Drug Combination

To determine the association between anti-infective exposure during the last two trimesters of pregnancy and the risk of small-for-gestational-age (SGA) newborns.. Case-control study within the Québec Pregnancy Registry.. Province of Québec, Canada.. Analyses were performed on prospectively collected data of 63,338 pregnant women that met eligibility criteria for the study (8192 cases and 55,146 controls).. Unconditional logistic regression models were used to quantify the association between exposure to anti-infective drugs and the risk of SGA.. A case of SGA was defined as a pregnancy resulting in a baby that weighs below the tenth percentile, adjusted for gestational age and gender, according to the Canadian gender-specific reference curves. A control was defined as a pregnancy resulting in a baby that weighs greater or equal to the tenth percentile, adjusted for gestational age and gender.. Exposure to all combined anti-infective drugs was not associated with the risk of SGA (OR 0.97; 95% CI 0.91-1.04). The use of sulfamethoxazole/trimethoprim was associated with SGA (OR 1.61; 95% CI 1.16-2.23), whereas the use of urinary anti-infective drugs decreased the risk (OR 0.80; 95% CI 0.65-0.97).. Exposure to sulfamethoxazole/trimethoprim during the last two trimesters of pregnancy was associated with SGA. Further research is needed to address the use of other therapeutic alternatives in the management of infections that predispose infants being born SGA in pregnant women with other risk factors for this condition.

Topics: Adult; Anti-Infective Agents; Case-Control Studies; Female; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Small for Gestational Age; Logistic Models; Odds Ratio; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prevalence; Quebec; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

In previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy.. We used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents.. We included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole-trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39-1.66), severe preeclampsia (OR 1.77, 95% CI 1.38-2.28), placental abruption (OR 1.32, 95% CI 1.12-1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01-1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11-1.34) and fetal death (OR 1.35, 95% CI 1.07-1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results.. Maternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.

Topics: Abruptio Placentae; Adult; Cohort Studies; Female; Fetal Death; Fetal Growth Retardation; Folic Acid Antagonists; Humans; Maternal Exposure; Phenobarbital; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Retrospective Studies; Saskatchewan; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

Q fever is a zoonosis caused by Coxiella burnetii. During pregnancy, it may result in obstetric complications, such as spontaneous abortion, intrauterine growth retardation, intrauterine fetal death, and premature delivery. Pregnant women are exposed to the risk of chronic Q fever.. We included 53 pregnant women who received a diagnosis of Q fever. We compared the incidence of obstetric and maternal Q fever complications for women who received long-term cotrimoxazole treatment (n=16) with that for women who did not receive long-term cotrimoxazole treatment (n=37); long-term cotrimoxazole treatment was defined as oral administration of trimethoprim-sulfamethoxazole during at least 5 weeks of pregnancy.. Obstetric complications were observed in 81.1% of pregnant women who did not receive long-term cotrimoxazole therapy: 5 (13.5%) women experienced spontaneous abortions, 10 (27%) experienced intrauterine growth retardation, 10 (27%) experienced intrauterine fetal death, and 10 (27%) experienced premature delivery. Oligoamnios was observed in 4 patients (10.8%). Obstetric complications were found to occur significantly more often in patients infected during their first trimester of pregnancy than in those infected later (P=.032). The outcome of the pregnancy was found to depend on placental infection by C. burnetii (P=.013). Long-term cotrimoxazole treatment protected against maternal chronic Q fever (P=.001), placental infection (P=.038), and obstetric complications (P=.009), especially intrauterine fetal death (P=.018), which was found to be related to placental infection (P=.008).. Q fever during pregnancy results in severe obstetric complications, including oligoamnios. Because of its ability to protect against placental infection, intrauterine fetal death, and maternal chronic Q fever, long-term cotrimoxazole treatment should be used to treat pregnant women with Q fever.

Topics: Abortion, Spontaneous; Adolescent; Adult; Anti-Infective Agents; Coxiella burnetii; Drug Administration Schedule; Female; Fetal Death; Fetal Growth Retardation; Follow-Up Studies; France; Humans; Placenta; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Q Fever; Retrospective Studies; Trimethoprim, Sulfamethoxazole Drug Combination