UNASSIGNED: Drug exposure during pregnancy is frequent, even more during first trimester as pregnant women might not be aware of their condition. We used available electronic health records (EHRs) to describe the use of medications during the first trimester in pregnant women and to compare drug exposure between those women who had an abortion (either elective or spontaneous) compared to those who had live births.
UNASSIGNED: Case-control study of abortions, either elective or spontaneous (cases), and live birth pregnancies (controls) in Sistema d\'Informació per al Desenvolupament de la Investigació en Atenció Primària (Catalan Primary Health electronic health records) from 2012 to 2020. Exposure to drugs during first trimester of pregnancy was considered to estimate the association with abortion by conditional logistic regression and adjusted by health conditions and other drugs exposure.
UNASSIGNED: Sixty thousand three hundred fifty episodes of abortions were matched to 118,085 live birth pregnancy episodes. Cases had higher rates of alcohol intake (9.9% vs. 7.2%, p < 0.001), smoking (4.5% vs. 3.6%, p < 0.001), and previous abortions (9.9% vs. 7.8%, p < 0.001). Anxiety (30.3% and 25.1%, p < 0.001), respiratory diseases (10.6% and 9.2%, p < 0.001), and migraine (8.2% and 7.3%, p < 0.001), for cases and controls, respectively, were the most frequent baseline conditions. Cases had lower rate of drug exposure, 40,148 (66.5%) versus 80,449 (68.1%), p < 0.001. Association with abortion was found for systemic antihistamines (adjusted odds ratio [ORadj] 1.23, 95% confidence interval [CI] 1.19-1.27), antidepressants (ORadj 1.11, 95% CI 1.06-1.17), anxiolytics (ORadj 1.31, 95% CI 1.26-1.73), and nonsteroidal anti-inflammatory drugs (ORadj 1. 63, 95% CI 1.59-1.67).
UNASSIGNED: These high rates of drug exposures during the first trimester of pregnancy highlights the relevance of informed prescription to women with childbearing potential.

BACKGROUND: Massive fetomaternal hemorrhage (FMH) is a rare event during pregnancy that may cause severe fetal anemia or death.
METHODS: This paper reports two cases of fetomaternal hemorrhage with unexplained reasons. Both cases required emergency caesarean sections for non-reassuring fetal status and were treated with neonatal blood transfusion. Fetomaternal hemorrhage was confirmed via maternal Kleihauer-Betke test.
CONCLUSIONS: We found parenchymal pallor, increased nucleated red blood cells (nRBCs), and syncytial knots (SKs) in the placentas, which are compatible with fetal anemia. Immunohistochemical staining indicated VEGF, CD34, and CD31 expression in the endothelial cells of the capillaries, characteristic of massive FMH placenta. This article also reviews the particular histopathological changes in FHM placenta according to the placental lesion classification system.

暂无摘要。

ABO blood type incompatibility hemolytic disease of newborn (ABO-HDN) and drug-induced immune hemolytic anemia (DIIHA) due to non-immunologic protein adsorption (NIPA) mainly cause extravascular hemolysis. All the reported severe DIIHA were caused by drug-induced antibodies, and rare report of acute intravascular hemolysis was caused by the NIPA mechanism or ABO-HDN.
We report the first case of acute intravascular hemolysis induced by cefotaxime sodium - sulbactam sodium (CTX - SBT) in a case of ABO-HDN which resulted in death at 55 h after birth. The mother\'s blood type was O and RhD-positive, and the newborn\'s blood type was B and RhD-positive. No irregular red blood cell (RBC) antibodies or drug-dependent antibodies related to CTX or SBT was detected in the mother\'s plasma and the plasma or the RBC acid eluent of the newborn. Before the newborn received CTX - SBT treatment, the result of direct antiglobulin test (DAT) was negative while anti-B was positive (2 +) in both plasma and acid eluent. After the newborn received CTX - SBT treatment, the results of DAT for anti-IgG and anti-C3d were both positive, while anti-B was not detected in plasma, but stronger anti-B (3 +) was detected in acid eluent. In vitro experiments confirmed that NIPA of SBT promoted the specific binding of maternal-derived IgG anti-B to B antigen on RBCs of the newborn, thereby inducing acute intravascular hemolysis.
The NIPA effect of SBT promoted the specific binding of mother-derived IgG anti-B in newborn\'s plasma to the newborn\'s RBC B antigens and formed an immune complex, and then activated complement, which led to acute intravascular hemolysis. Drugs such as SBT with NIPA effect should not be used for newborns with HDN.

BACKGROUND: Euglycaemic ketoacidosis (EKA) is an infrequent but serious condition which usually follows a period of starvation, severe vomiting or illness in individuals with or without diabetes. Ketoacidosis is associated with materno-fetal morbidity and mortality necessitating prompt diagnosis and management. Physiological increases in insulin resistance render pregnancy a diabetogenic state with increased susceptibility to ketosis. COVID-19 is associated with worse clinical outcomes in patients with diabetes and is an independent risk factor for ketoacidosis in normoglycaemic individuals.
METHODS: We describe two cases of SARS-CoV-2 positive pregnant women presenting with normoglycaemic metabolic ketoacidosis. Both cases were associated with maternal and fetal compromise, requiring aggressive fluid and insulin resuscitation and early delivery.
CONCLUSIONS: We discuss possible physiology and propose a management strategy for euglycaemic ketoacidosis in pregnancy.

Prenatal exposure to heavy metals is implicated in the etiology of birth defects. We investigated whether concentrations of cadmium (Cd) and lead (Pb) in umbilical cord tissue are associated with risk for neural tube defects (NTDs) and whether selected genetic variants of the fetus modify their associations.
This study included 166 cases of NTD fetuses/newborns and 166 newborns without congenital malformations. Umbilical cord tissue was collected at birth or elective pregnancy termination. Cd and Pb concentrations were assessed by inductively coupled plasma-mass spectrometry, and 20 single-nucleotide polymorphisms (SNPs) in 9 genes were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the risk for NTDs in association with metal concentrations or genotype using logistic regression. Multiplicative-scale interactions between the metals and genotypes on NTD risk were assessed with logistic regression, and additive-scale interactions were estimated with a non-linear mixed effects model.
Higher concentrations of Cd were observed in the NTD group than in the control group, but no difference was found for Pb. Concentrations of Cd above the median level showed a risk effect, while the association between Pb and NTD risk was not significant in univariate analyses. The association of Cd was attenuated after adjusting for periconceptional folic acid supplementation. Fetuses with the AG and GG genotypes of rs4880 in SOD2 (superoxide dismutase 2) tended to have a lower risk, but fetuses with the CT and TT genotypes of rs1801133 in MTHFR (5,10-methylenetetrahydrofolatereductase) have a higher risk for NTDs when compared to their respective wild-type. rs4880 and Cd exhibited a multiplicative-scale interaction on NTD risk: the association between higher Cd and the risk for NTDs was increased by over fourfold in fetuses carrying the G allele [OR 4.43 (1.30-15.07)] compared to fetuses with the wild-type genotype. rs1801133 and Cd exposure showed an additive interaction, with a significant relative excess risk of interaction [RERI 0.64 (0.02-1.25)].
Prenatal exposure to Cd may be a risk factor for NTDs, and the risk effect may be enhanced in fetuses who carry the G allele of rs4880 in SOD2 and T allele of rs1801133 in MTHFR.

BACKGROUND: Natalizumab is a monoclonal antibody approved for the treatment of patients with relapsing-remitting multiple sclerosis. According to the current clinical recommendations, its use during pregnancy should be carefully evaluated only in women with highly active disease who plan a pregnancy or have an unplanned pregnancy, after accurate counseling about eventual maternal disease relapse due to therapy suspension.
METHODS: This brief case report describes a case of documented anemia that we observed in a newborn whose mother with relapsing-remitting multiple sclerosis was treated with an extended dosing protocol of natalizumab throughout pregnancy. The newborn received the infusion of erythropoietin every seven days from the fortieth day of life; subsequently, the status of anemia underwent clinical resolution.
CONCLUSIONS: This case report confirmed that natalizumab can cause disorders of hematopoiesis, including anemia, thrombocytopenia, or pancytopenia, in newborns of patients treated during pregnancy. A multidisciplinary team, including experienced pediatricians and pediatric hematologists, has a critical role in managing newborns delivered by women, being treated with natalizumab for treating relapsing-remitting multiple sclerosis during pregnancy.

We describe a case of maternal acetaminophen toxicity leading to Caesarean section delivery of a pre-term neonate with acetaminophen-induced hepatic injury and encephalopathy at 33 weeks gestational age. Delayed treatment with N-acetylcysteine (NAC) was initiated in the baby 11 h after delivery, with eventual discharge of a healthy baby at 12 days of age. The baby was treated with a standard but extended duration NAC protocol. Post-operatively, liver biopsy of the mother demonstrated acetaminophen-induced hepatic injury overlying mild hepatic steatosis. This was also managed with NAC therapy leading to complete clinical resolution of acetaminophen induced hepatic injury and discharge on post-operative day 10. This case of delayed NAC therapy for the treatment of pre-term neonatal acetaminophen toxicity is one of very few reported in the literature and can be used as a guide in the management of subsequent cases.

Acquired hemophilia due to inhibitor antibodies to factor VIII (FVIII) is a very rare entity in neonatal period. Maternal IgG antibodies may cross the placenta and can cause life-threatening hemorrhages in newborns. Here, we represent a newborn who diagnosed as a transplacental acquired hemophilia A. A very high titer of inhibitor level (320 Nijmegen-Bethesda unit) was detected in plasma due to transplasental transfer in this case. According to the best of our knowledge the baby had the highest inhibitor level in neonatal period in the literature. Bleeding complications including intracranial hemorrhage secondary to this condition were reported before. Therefore, to prevent possible life complications, prophylactic recombinant FVIIa was administered in the presenting case and any bleeding event was not observed during follow-up. In conclusion, using prophylactic recombinant FVIIa in newborns is a safe choice for transplacental acquired hemophilia A.

A number of epidemiologic studies with a variety of exposure assessment approaches have implicated pesticides as risk factors for childhood cancers. Here we explore the association of pesticide exposure in pregnancy and early childhood with childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) utilizing land use and pesticide use data in a sophisticated GIS tool.
We identified cancer cases less than 6 years of age from the California Cancer Registry and cancer-free controls from birth certificates. Analyses were restricted to those living in rural areas and born 1998-2011, resulting in 162 cases of childhood leukemia and 9,805 controls. Possible carcinogens were selected from the Environmental Protection Agency\'s classifications and pesticide use was collected from the California Department of Pesticide Regulation\'s (CDPR) Pesticide Use Reporting (PUR) system and linked to land-use surveys. Exposures for subjects were assessed using a 4000m buffer around the geocoded residential addresses at birth. Unconditional logistic and hierarchical regression models were used to assess individual pesticide and pesticide class associations.
We observed elevated risks for ALL with exposure to any carcinogenic pesticide (adjusted Odds Ratio (aOR): 2.83, 95% CI: 1.67-4.82), diuron (Single-pesticide model, adjusted (OR): 2.38, 95% CI: 1.57-3.60), phosmet (OR: 2.10, 95% CI: 1.46-3.02), kresoxim-methyl (OR: 1.77, 95% CI: 1.14-2.75), and propanil (OR: 2.58, 95% CI: 1.44-4.63). Analyses based on chemical classes showed elevated risks for the group of 2,6-dinitroanilines (OR: 2.50, 95% CI: 1.56-3.99), anilides (OR: 2.16, 95% CI: 1.38-3.36), and ureas (OR: 2.18, 95% CI: 1.42-3.34).
Our findings suggest that in rural areas of California exposure to certain pesticides or pesticide classes during pregnancy due to residential proximity to agricultural applications may increase the risk of childhood ALL and AML. Future studies into the mechanisms of carcinogenicity of these pesticides may be beneficial.