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Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

Objective: Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years., Study Design: This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 μg/L were considered iodine sufficient, and concentrations of 150 μg/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years., Results: A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 μg/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84-105] vs. 96 [87-109], P adj  = 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 - 102] and 91 [81 - 100], P adj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status ( p  > 0.05)., Conclusion: Maternal urinary iodine concentrations ≤150 μg/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia., Key Points: · Most pregnant patients with subclinical thyroid disease are iodine sufficient.. · Mild maternal iodine insufficiency is not associated with lower offspring IQ at 5 years.. · Iodine supplementation in subclinical thyroid disease is unlikely to improve IQ.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To estimate temporal trends of stroke in the peripartum period and to assess the relationship between stroke and maternal adverse outcomes vis-à-vis timing and hypertension., Methods: We conducted a retrospective, cross-sectional study using the National Inpatient Sample to identify hospitalizations with pregnancy-associated stroke in the United States (2016-2019). Temporal trends in pregnancy-associated stroke were examined according to timing of stroke (antepartum vs postpartum) and both prepregnancy and pregnancy hypertensive disorders (yes vs no). Multivariable Poisson regression models with robust error variance were used to examine the association among maternal adverse outcomes, timing of stroke, and hypertensive disorders., Results: Among 15,977,644 pregnancy hospitalizations, 6,100 hospitalizations (38.2/100,000 hospitalizations) were with pregnancy-associated stroke. Of these, 3,635 (59.6%) had antepartum pregnancy-associated stroke and 2,465 (40.4%) had postpartum pregnancy-associated stroke; alternatively, 2,640 (43.3%) had hypertensive disorders, and 3,460 (56.7%) were without hypertensive disorders. From 2016 to 2019, the overall rate of pregnancy-associated stroke (37.5 to 40.8/100,000 pregnancy hospitalizations, P =.028), rate of postpartum pregnancy-associated stroke (14.6 to 17.6/100,000 pregnancy hospitalizations, P =.005), and rate of pregnancy-associated stroke with hypertensive disorders (14.9 to 17.2/100,000 pregnancy hospitalizations, P =.013) increased. Antepartum pregnancy-associated stroke and pregnancy-associated stroke without hypertensive disorders, however, remained stable. Despite higher risk of maternal morbidity in postpartum stroke hospitalizations, including mechanical ventilation and pneumonia, there was no significant difference in in-hospital mortality between antepartum and postpartum stroke. Similarly, between pregnancy-associated stroke with hypertensive disorders and stroke without hypertensive disorders, an increased risk of mechanical ventilation, seizure, and prolonged hospital stay was seen for stroke with hypertensive disorders without an increase in mortality., Conclusion: A nationally representative sample of hospitalizations in the United States indicates an increasing trend in the rate of postpartum stroke. Almost half of hospitalizations with pregnancy-associated stroke have concomitant hypertensive disorders. Risk of adverse outcomes, but not mortality, is elevated in patients with stroke occurring in the postpartum period and stroke associated with hypertensive disorders., Competing Interests: Financial Disclosure Natalie Neff disclosed her institution received funding from the Society for Maternal-Fetal Medicine (SMFM) for a Danielle Peress grant, which was not used for this submission but is being used for a completely different research project on preeclampsia. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Insulin detemir, being used increasingly during pregnancy, may have pharmacologic benefits compared with neutral protamine Hagedorn., Objective: We evaluated the probability that compared with treatment with neutral protamine Hagedorn, treatment with insulin detemir reduces the risk for adverse neonatal outcome among individuals with type 2 or overt type 2 diabetes mellitus (gestational diabetes mellitus diagnosed at <20 weeks' gestation)., Study Design: We performed a multiclinic randomized controlled trial (September 2018 to January 2020), which included women with singleton gestation with type 2 or overt type 2 diabetes mellitus who sought obstetrical care at ≤21 weeks' gestation. Participants were randomized to receive either insulin detemir or neutral protamine Hagedorn by a clinic-stratified scheme. The primary outcome was a composite of adverse neonatal outcomes, including shoulder dystocia, large for gestational age, neonatal intensive care unit admission, respiratory distress (defined as the need of at least 4 hours of respiratory support with supplemental oxygen, continuous positive airway pressure or ventilation at the first 24 hours of life), or hypoglycemia. The secondary neonatal outcomes included gestational age at delivery, small for gestational age, 5-minute Apgar score of <7, lowest glucose level, need for intravenous glucose, respiratory distress syndrome, need for mechanical ventilation or continuous positive airway pressure, neonatal jaundice requiring therapy, brachial plexus injury, and hospital length of stay. The secondary maternal outcomes included hypoglycemic events, hospital admission for glucose control, hypertensive disorder of pregnancy, maternal weight gain, cesarean delivery, and postpartum complications. We used the Bayesian statistics to estimate a sample size of 108 to have >75% probability of any reduction in the primary outcome, assuming 80% power and a hypothesized effect of 33% reduction with insulin detemir. All analyses were intent to treat under a Bayesian framework with neutral priors (a priori assumed a 50:50 likelihood of either intervention being better; National Clinical Trial identifier 03620890)., Results: There were 108 women randomized in this trial (57 in insulin detemir and 51 in neutral protamine Hagedorn), and 103 women were available for analysis of the primary outcome (n=5 for pregnancy loss before 24 weeks' gestation). Bayesian analysis indicated an 87% posterior probability of reduced primary outcome with insulin detemir compared with neutral protamine Hagedorn (posterior adjusted relative risk, 0.88; 95% credible interval, 0.61-1.12). Bayesian analyses for secondary outcomes showed consistent findings of lower adverse maternal outcomes with the use of insulin detemir vs neutral protamine Hagedorn: for example, maternal hypoglycemic events (97% probability of benefit; posterior adjusted relative risk, 0.59; 95% credible interval, 0.29-1.08) and hypertensive disorders (88% probability of benefit; posterior adjusted relative risk, 0.81; 95% credible interval, 0.54-1.16)., Conclusion: In our comparative effectiveness trial involving individuals with type 2 or overt type 2 diabetes mellitus, use of insulin detemir resulted in lower rates of adverse neonatal and maternal outcomes compared with neutral protamine Hagedorn., (Published by Elsevier Inc.)

Objective: This study aimed to compare the maternal and neonatal adverse outcomes among singletons delivered at 36 weeks or later with cerclage during index pregnancy versus those without cerclage., Study Design: This retrospective cohort study utilized the U.S. vital statistics datasets from 2011 to 2013. Inclusion criteria were women with nonanomalous singletons, with and without cerclage placement, without diabetes or hypertensive disorders, and delivered at 36 to 41 weeks. The coprimary outcomes were composite maternal and neonatal adverse outcomes. Composite maternal adverse outcome included admission to intensive care unit, maternal transfusion, ruptured uterus, unplanned hysterectomy, or unplanned operating room procedure. Composite neonatal adverse outcome included Apgar score less than 5 at 5 minutes, assisted ventilation for more than 6 hours, neonatal seizure, birth injury, or neonatal death. Secondary outcomes were chorioamnionitis and cesarean delivery. Multivariable Poisson's regression models with error variance were used while adjusting for confounders. Adjusted relative risk (aRR) with 95% confidence intervals (CIs) were calculated., Results: Of the 8,508,228 women who met inclusion criteria, 0.2% had a cerclage and reached 36 weeks. Composite maternal (aRR: 2.04; 95% CI: 1.76-2.36) and neonatal (aRR: 1.28; 95% CI: 1.11-1.47) adverse outcomes were significantly higher among those with cerclage than those without cerclage. Chorioamnionitis (aRR: 1.47; 95% CI: 1.30-1.67) and cesarean delivery (aRR: 1.10; 95% CI: 1.08-1.12) were also significantly higher in women with cerclage than those without cerclage., Conclusion: There is an association between increased composite maternal and neonatal adverse outcomes among women with cerclage who delivered at 36 to 41 weeks as compared with those without cerclage., Key Points: · Cerclage is associated with increased composite maternal adverse outcome in women at 36-41 weeks.. · Cerclage is associated with increased composite neonatal adverse outcome in women at 36-41 weeks.. · Increased chorioamnionitis and cesarean delivery rates are associated with cerclage in women at 36-41 weeks.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: To compare composite maternal and neonatal adverse outcomes among women with at least a bachelor's degree by racial and ethnic groups., Methods: This was a retrospective cohort study using the U.S. vital statistics data sets. We included women with at least a bachelor's degree who delivered a nonanomalous live singleton neonate at 24-40 weeks. The primary outcome, composite maternal adverse outcome, included admission to intensive care unit, maternal transfusion, ruptured uterus, unplanned hysterectomy, or unplanned operating room procedure after delivery. The secondary outcome, composite neonatal adverse outcome, included 5-minute Apgar score less than 5, assisted ventilation for more than 6 hours, neonatal seizure, birth injury, or neonatal death. Multivariable regression models were used to estimate the association between maternal race and adverse outcomes., Results: Of 11.8 million live births, 2.2 million (19%) met the inclusion criteria; 81.5% were to non-Hispanic white women, 8.5% to non-Hispanic black women, and 10% Hispanic women. The overall rate of composite maternal adverse outcome was 5.3 per 1,000 live births. Compared with non-Hispanic white women, the risk of the composite maternal adverse outcome was significantly higher among non-Hispanic black women (adjusted relative risk [aRR] 1.20; 95% CI 1.13-1.27), but lower among Hispanic women (aRR 0.69; 95% CI 0.64-0.74), a pattern which varied among different gestational age groups. The overall rate of composite neonatal adverse outcome was 11.6 per 1,000 live births. The risk of composite neonatal adverse outcome was significantly higher among neonates with non-Hispanic black mothers (aRR 1.25; 95% CI 1.20-1.30), but lower among neonates with Hispanic mothers (aRR 0.71; 95% CI 0.68-0.75), compared with neonates delivered by non-Hispanic white mothers and varied across gestational age., Conclusion: Among women with at least a bachelor's degree, small but measurable racial and ethnic disparities in composite maternal and neonatal adverse outcomes.

Objective: To estimate the effect of antenatal treatment of subclinical hypothyroidism on maternal depressive symptoms., Methods: We conducted an ancillary study to a multicenter trial in women with singleton pregnancies diagnosed with subclinical hypothyroidism randomized to antenatal thyroxine therapy or placebo. Treatment was discontinued at the end of pregnancy. Women with overt thyroid disease, diabetes, autoimmune disease, and those diagnosed with depression were excluded. Participants were assessed for depressive symptoms using the Center for Epidemiological Studies-Depression scale (CES-D) before starting the study drug (between 11 and 20 weeks of gestation), between 32 and 38 weeks of gestation, and at 1 year postpartum. The primary outcome was maternal depressive symptoms score as assessed using the CES-D. Secondary outcome was the percentage of women who scored 16 or higher on the CES-D, as such a score is considered screen-positive for depression., Results: Two hundred forty-five (36.2% of parent trial) women with subclinical hypothyroidism were allocated to thyroxine (n=124) or placebo (n=121). Median CES-D scores and the proportion of participants with positive scores were similar at baseline between the two groups. Treatment with thyroxine was not associated with differences in CES-D scores (10 [5-15] vs 10 [5-17]; P=.46) or in odds of screening positive in the third trimester compared with placebo, even after adjusting for baseline scores (24.3% vs 30.1%, adjusted odds ratio 0.63, 95% CI 0.31-1.28, P=.20). At 1 year postpartum, CES-D scores were not different (6 [3-11] vs 6 [3-12]; P=.79), nor was the frequency of screen-positive CES-D scores in the treated compared with the placebo group (9.7% vs 15.8%; P=.19). Treatment with thyroxine during pregnancy was also not associated with differences in odds of screening positive at the postpartum visit compared with placebo even after adjusting for baseline scores. Sensitivity analysis including women who were diagnosed with depression by the postpartum visit did not change the results., Conclusions: This study did not achieve its planned sample size, thus our conclusions may be limited, but in this cohort of pregnant women with subclinical hypothyroidism, antenatal thyroxine replacement did not improve maternal depressive symptoms.

Background: Inositols (INOs) supplementation during pregnancy, specifically the combination of myo-inositol (MI) and D-chiro-inositol (DCI), has been reported to improve vascular parameters in women with gestational diabetes mellitus. We demonstrated previously that offspring born to pregnant mice lacking the endothelial nitric oxide synthase (eNOS+/-) gene have hypertension (HTN) as adults and, when fed a high-fat diet (HFD), develop a metabolic syndrome (MS) phenotype., Objective: Our aim was to evaluate whether INOs treatment in pregnancy complicated by MS improves the vascular and metabolic profile in mice offspring programmed in utero to develop HTN and MS., Materials and Methods: Heterozygous eNOS+/- mice fed an HFD manifest a MS phenotype. Female eNOS+/- mice with MS were bred with a wild-type (WT) male. On gestational day 1, pregnant females were randomly allocated to receive either a mixture of INOs (MI/DCI: 7.2/0.18 mg/mL) or water as placebo until delivery. The female offspring obtained were genotyped and categorized as: WT (genetically normal, with eNOS gene) and eNOS+/- offspring (genetically modified, heterozygous for eNOS gene). Both offspring developed in an abnormal uterine environment due to maternal MS. At 9-10 weeks of age, the offspring underwent a glucose tolerance test (GTT) and systolic blood pressure (SBP) measurement. The mice were then sacrificed, and the carotid arteries were isolated for evaluation of vascular responses. Responses to phenylephrine (PE), in the presence and absence of a nonspecific nitric oxide inhibitor (N-nitro-L-arginine methyl ester [L-NAME]), the vasodilator acetylcholine (ACh), and sodium nitroprusside (SNP) were assessed., Results: The GTT showed lower glucose levels in both eNOS+/-INOs (P = .03) and WT-INOs (P = .05) offspring born to MS dams on INOs supplementation compared to offspring born to untreated dams. SBP was higher in eNOS+/- offspring compared to WT (169 ± 7 vs 142 ± 9 mm Hg, respectively, P = .04) and INOs treatment decreased SBP in WT-INOs (110 ± 10 mm Hg, P = .01) but not in eNOS+/-INOs offspring. Maximal (%Max) contractile response to PE was higher in eNOS+/- offspring born to MS dams and was decreased in those born to MS dams treated with INOs (%Max, eNOS+/-, 123 ± 7 vs eNOS+/-INOs, 82 ± 11 mm Hg, P = .007). No differences were seen in PE contractile responses in WT offspring born to MS dams treated or not treated with INOs (WT, 92 ± 4 vs WT-INOs, 75 ± 7). The L-NAME response was decreased in eNOS+/-INOs and WT-INOs offspring compared to untreated ones. The ACh vasorelaxation was impaired in eNOS+/- and WT offspring born to MS dams, and maternal INOs treatment improved offspring vascular relaxation in both offspring (P = .01 and P = .03, respectively). No differences were seen in response to SNP., Conclusion: Inositols supplementation improved glucose tolerance, SBP, and vascular responses in adult eNOS+/- and WT offspring born to dams with MS. Interestingly, WT born to MS dams show an altered vascular profile similar to eNOS+/- offspring and exhibit an improved response to INOs treatment. Our findings suggest that the benefits of INOs treatment are more pronounced in offspring exposed to environmental factors in utero, and less likely in those due to genetic factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to evaluate obstetric outcomes in relation to the extent of donor sperm exposure with and without egg donation., Materials and Methods: This is a retrospective cohort study in a single tertiary care center. All women with a singleton pregnancy who conceived following sperm donation (SD) were included. Obstetrics and neonatal outcomes for pregnancies following single SD were compared with pregnancies following repeat SD from the same donor. In a secondary analysis, we compared pregnancy outcomes among three modes of assisted reproductive technology (intrauterine insemination [IUI-SD], in vitro fertilization [IVF-SD], and IVF sperm + egg donation [IVF-SD + ED])., Results: A total of 706 pregnant women met the inclusion criteria, 243 (34.4%) following the first SD and 463 (65.6%) following repeat donations. Compared with repeat SDs, single donation was not associated with higher rates of preterm delivery (12.8 vs. 12.7%, respectively, p  = 0.99), preeclampsia (7.0 vs. 6.9%, p  = 0.999), and intrauterine growth restriction (4.1 vs. 3.9%, p  = 0.88). Pregnancies following IVF-SD + ED had increased risk for preeclampsia (adjusted odds ratio [AOR], 3.1; 95% confidence interval [CI], 1.5-6.6), preterm labor (AOR, 2.4; 95% CI, 1.1-5.4), and cesarean section (AOR, 2.1; 95% CI, 1.0-4.3) compared with IUI-SD and IVF-SD., Conclusion: The extent of donor sperm exposure did not correlate with obstetrics complications, but double gamete donation was associated with increased risk for preeclampsia, preterm labor, and cesarean section., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To compare Pfannenstiel versus vertical skin incision for the prevention of cesarean wound complications in morbidly obese women., Study Design: Women with body mass index ≥ 40 kg/m 2 undergoing cesarean delivery (CD) were randomly allocated to Pfannenstiel or vertical skin incision. The primary outcome was a wound complication within 6 weeks. Due to a low consent rate, we limited enrollment to a defined time period for feasibility. We conducted a traditional frequentist analysis with log-binomial regression to obtain relative risks (RRs), and a Bayesian analysis to estimate the probability of treatment benefit. A priori, we decided that a ≥60% probability of treatment benefit for either incision type would be convincing evidence to pursue a larger trial., Results: A total of 648 women were approached, 228 were consented, and 91 were randomized. The primary outcome rate was 19% in the Pfannenstiel group and 21% in the vertical group (RR: 1.18; 95% confidence interval: 0.49-2.85). Bayesian analysis revealed a 59% probability that Pfannenstiel had a lower primary outcome rate., Conclusion: In the first published randomized trial to compare skin incision types for obese women undergoing CD, we were unable to demonstrate differences in clinical outcomes. Our trial suggests that a larger study would have a low probability for different findings., Trial Registration: NCT 01897376 (www.clinicaltrials.gov)., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: To assess whether treatment of pregnant women with subclinical hypothyroidism or hypothyroxinemia alters neonatal TSH results., Study Design: A planned secondary analysis of data from two multi-center randomized, double-masked, placebo-controlled thyroxine replacement trials in pregnant women with either subclinical hypothyroidism or hypothyroxinemia. Infant heel-stick specimens were obtained before discharge. We compared TSH levels between neonates born to mothers allocated to treatment or placebo within each trial and between neonates in the placebo groups. Multiples of means were generated for day-of-life-specific data., Results: Neonatal TSH values were available for 573/677 (84.6%) newborns from the subclinical hypothyroidism trial and 461/526 (87.6%) newborns from the hypothyroxinemia trial. Neonatal TSH values did not differ in either trial by treatment group or between placebo groups (P > 0.05 for all comparisons)., Conclusions: Neonatal TSH values did not differ with thyroid hormone replacement in pregnancies diagnosed with subclinical hypothyroidism or hypothyroxinemia.

Background: Subclinical thyroid disease during pregnancy may be associated with adverse outcomes, including a lower-than-normal IQ in offspring. It is unknown whether levothyroxine treatment of women who are identified as having subclinical hypothyroidism or hypothyroxinemia during pregnancy improves cognitive function in their children., Methods: We screened women with a singleton pregnancy before 20 weeks of gestation for subclinical hypothyroidism, defined as a thyrotropin level of 4.00 mU or more per liter and a normal free thyroxine (T 4 ) level (0.86 to 1.90 ng per deciliter [11 to 24 pmol per liter]), and for hypothyroxinemia, defined as a normal thyrotropin level (0.08 to 3.99 mU per liter) and a low free T 4 level (<0.86 ng per deciliter). In separate trials for the two conditions, women were randomly assigned to receive levothyroxine or placebo. Thyroid function was assessed monthly, and the levothyroxine dose was adjusted to attain a normal thyrotropin or free T 4 level (depending on the trial), with sham adjustments for placebo. Children underwent annual developmental and behavioral testing for 5 years. The primary outcome was the IQ score at 5 years of age (or at 3 years of age if the 5-year examination was missing) or death at an age of less than 3 years., Results: A total of 677 women with subclinical hypothyroidism underwent randomization at a mean of 16.7 weeks of gestation, and 526 with hypothyroxinemia at a mean of 17.8 weeks of gestation. In the subclinical hypothyroidism trial, the median IQ score of the children was 97 (95% confidence interval [CI], 94 to 99) in the levothyroxine group and 94 (95% CI, 92 to 96) in the placebo group (P=0.71). In the hypothyroxinemia trial, the median IQ score was 94 (95% CI, 91 to 95) in the levothyroxine group and 91 (95% CI, 89 to 93) in the placebo group (P=0.30). In each trial, IQ scores were missing for 4% of the children. There were no significant between-group differences in either trial in any other neurocognitive or pregnancy outcomes or in the incidence of adverse events, which was low in both groups., Conclusions: Treatment for subclinical hypothyroidism or hypothyroxinemia beginning between 8 and 20 weeks of gestation did not result in significantly better cognitive outcomes in children through 5 years of age than no treatment for those conditions. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00388297 .).

During the past decade, prophylactic doses of low-molecular-weight heparin (LMWH) have been suggested to decrease the risk of placental-mediated complications. Herein, we review the prospective randomized trials that addressed the usefulness of LMWH in preventing placental-mediated complications in high-risk women. Inclusion criteria and results of these trials are heterogeneous. Unlike older trials (3 of 4 are single center), recent trials (all are multicenter) do not show beneficial effect of LMWH. There is certainly a need of complementary research before stating on the usefulness of LMWH in the prevention of placenta-mediated pregnancy complications in women at high risk.

Catastrophic antiphospholipid syndrome (CAPS) is an accelerated form of the antiphospholipid antibody syndrome resulting in multi-organ ischemia and failure. It is a rare and life-threatening condition that can be easily mistaken with hemolysis elevated liver enzymes low platelets syndrome, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome. In order to make a diagnosis, it is required to have multi-organ thrombosis over 1 week affecting at least three organs or systems, and to have positive antiphospholipid antibody on two occasions (6 weeks apart), and histopathologic confirmation of small vessel occlusion. However, due to similarities in clinical and laboratory findings between CAPS and some other obstetric complications, potential misdiagnosis or delay in diagnosis are common, increasing the risk of adverse maternal and perinatal outcomes. In this review we summarized information presented in previous studies, focusing on CAPS related to pregnancy. We reviewed diagnostic criteria, differential diagnosis, and common presentation ranging from malaise, abdominal pain, dyspnea, hypertension, to altered mental status and seizures. We also discussed management in pregnancy and included a detailed algorithm with steps to take. Of note, the most significant reduction in mortality was seen in patients receiving triple therapy which will be discussed in this review.

Background: Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype., Objective: The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model., Study Design: Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice., Results: Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo-treated obese pregnant mice. Pregnant metabolic-like syndrome mice treated with myoinositol/D-chiroinositol showed lower glucose values during the glucose tolerance test and in the area under the curve (myoinositol/D-chiroinositol: 17512.5 ± 3984.4 vs placebo: 29687.14 ± 8258.7; P = .003), but no differences were seen in the obese pregnant mice. Leptin serum levels were lower in the metabolic-like syndrome-myoinositol/D-chiroinositol-treated mice compared with the placebo group (myoinositol/D-chiroinositol: 16985 ± 976.4 pg/dL vs placebo: 24181.9 ± 3128.2 pg/dL, P = .045). No other differences were seen in any of the remaining serum metabolic biomarkers studied in metabolic-like syndrome and in obese pregnant mice. Maternal weight gain was not different in the pregnant metabolic-like syndrome dams, whereas it was lower in the obese myoinositol/D-chiroinositol-treated dams compared with the placebo group (myoinositol/D-chiroinositol: 10.9 ± 0.5 g vs 12.6 ± 0.6 g, P = .04). Fetal and placental weights did not differ between myoinositol/D-chiroinositol-treated and nontreated pregnant dams with metabolic-like syndrome and obesity., Conclusion: Combined inositol treatment during pregnancy improves blood pressure, glucose levels at the glucose tolerance test, and leptin levels in pregnant dams with metabolic-like syndrome phenotype but not in obese pregnant dams. In addition, inositol treatment was associated with lower gestational weight gain in the obese but not in the metabolic-like syndrome pregnant dams., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective This study aims to determine the rate of gestational diabetes mellitus (GDM) in pregnancies complicated by chronic hypertension and to compare the adverse outcomes in chronic hypertensive pregnancies with and without GDM. Study Design A secondary analysis from a multicenter trial of low-dose aspirin for preeclampsia prevention in women with chronic hypertension. The rate of GDM was evaluated among singleton pregnancies complicated with chronic hypertension and grouped according to their GDM status. Pregnancy outcomes and rates of preterm delivery < 35 weeks and < 32 weeks, preeclampsia, indicated preterm birth, small for gestational age, abruptio placentae, and perinatal death were compared between those with and without GDM. A subgroup analysis comparing women who developed superimposed preeclampsia with and without GDM was studied. Multivariate logistic-regression analysis was used to adjust for potentially confounding factors. Results A total of 763 women met the inclusion criteria: 129 (17%) developed GDM. Parity, race, maternal baseline blood pressure, antihypertensive drug use, and assignment to low-dose aspirin were not significantly different between the groups with and without GDM. Using univariate analysis, maternal age (33 vs. 24%, p = 0.03) and body mass index (88 vs. 57%, p < 0.001) were higher in those who had GDM, whereas the rate of preterm delivery < 32 weeks (12 vs. 5%, p = 0.02) was higher among those without GDM. Using logistic-regression analysis, the rate of composite adverse outcomes (adjusted odds ratio [aOR], 0.77; 95% confidence interval [CI], 0.41-1.47) that included indicated preterm birth, small for gestational age, abruptio placentae, and perinatal death showed no significant differences.Superimposed preeclampsia developed in 34 (26%) women with GDM and in 182 (29%) without GDM. When superimposed preeclampsia was present, it developed at an earlier gestational age among the group without GDM (35 ± 5 vs. 37 ± 3 weeks, p = 0.003), and had higher rates of small for gestational age infants (18 vs. 3%, p = 0.03). After adjustment for confounders, only length of stay in neonatal intensive care unit was longer for those without GDM who developed superimposed preeclampsia (aOR, 0.42; 95% CI, 0.2-0.93). Conclusion Women with chronic hypertension are at a high risk for developing GDM. Outcomes in patients with chronic hypertension and GDM are not significantly different from those with chronic hypertension only., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Diabetes complicates 6 to 7% of all pregnancies in the United States. Poor glycemic control is associated with multiple immediate and long-term adverse effects on both the mother and fetus. Although uniformity exists in the antenatal management of this disease, there is a paucity of evidence-based studies upon which to dictate the optimal time of delivery among affected women. The potential risks of delayed neonatal pulmonary maturation including respiratory distress syndrome and transient tachypnea of the newborn associated with early delivery must be balanced with the increased incidence of fetal demise, overgrowth, and birth injury related to diabetes in late gestations. Even among diabetic women with optimal glycemic control, the risk of stillbirth in the third trimester is considerably higher than their normal counterparts. The current paradigm of delaying delivery to 39 weeks in women with controlled and uncomplicated diabetes has been challenged by recent evidence advocating delivery by 38 weeks to improve perinatal outcomes. However, additional well-designed and adequately powered prospective studies are needed to better understand the short- and long-term implications of the optimal timing of delivery in this high-risk population. This article reviews the most current literature regarding the optimal timing of delivery in pregnancies complicated by diabetes mellitus and gestational diabetes mellitus., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: This study aims to compare neonatal and long-term outcomes among preterm newborns from women with reported versus those who did not report substance abuse., Study Design: Secondary analysis of a trial of magnesium sulfate for cerebral palsy prevention. Cases were pregnant women who reported substance abuse, controls were those who denied it. Study outcomes included (1) composite neonatal morbidity, defined as any of the following: Apgar score ≤ 3 at 5 minutes, seizures, culture-proven sepsis, necrotizing enterocolitis grades 2 or 3, intraventricular hemorrhage grades 3 or 4, and/or death before discharge; (2) infant and childhood morbidity, defined as stillbirth or death by 1 year, or moderate/severe cerebral palsy by age of 2., Results: Among 1,972 women meeting the inclusion criteria, 197 (10%) reported substance abuse. Composite neonatal, infant, and childhood morbidity rates were similar between cases and controls. However, women reporting substance abuse who delivered between 32(0/7) and 36(6/7) weeks had a higher frequency of composite infant and childhood morbidity (6.5 vs. 1.0%; adjusted odds ratio, 6.5; 95% confidence interval, 1.14-36.99)., Conclusions: Preterm birth was associated with similar composite neonatal morbidity between cases and controls. After 32 weeks, self-reported substance abuse was associated with a sevenfold increase in the rates of stillbirth and long-term infant morbidity., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: Seizures in pregnancy are particularly challenging, as their management requires careful consideration of not only the etiology of the seizure, but also the physiologic changes of pregnancy as well as potential adverse effects on the developing embryo or fetus. Newer antiepileptic drugs (AEDs) have increasingly shown promising results of lower rate of teratogenesis, as well as better seizure control during pregnancy., Areas Covered: We performed a review of the scientific literature of seizures in pregnancy including status epilepticus as well as eclampsia, with a focus on safety of currently used AEDs. This covers the different generations of antiepileptic medications, their interactions and seizure recurrence preventative measures. In addition, we summarized our personal approach to the care for these women., Expert Opinion: In summary, morbidity associated with seizure in pregnancy is decreasing as treatments and supportive therapies have improved. The understanding of teratogenesis as well as novel targeted therapeutics will allow women on AEDs during their pregnancy, to receive the safest drug for their developing fetus as well as themselves.

Objective: To estimate the cost-effectiveness of a trial of labor after one previous cesarean (TOLAC) when incorporating long-term events and outcomes., Methods: A Markov model comparing TOLAC with elective repeat cesarean delivery (ERCD) was developed for a hypothetical cohort with no contraindication to a TOLAC. Women were selected from a prospective study to derive probability estimates for potential events through three subsequent pregnancies. Probabilities for cerebral palsy and stress urinary incontinence, cost data, and quality-adjusted life-years (QALYs) were obtained from the literature. The primary outcome was cost-effectiveness measured as the marginal cost per QALY gained, with a $50,000 threshold per QALY used to define cost-effectiveness., Results: The TOLAC strategy dominated the ERCD strategy at baseline, with $164.2 million saved and 500 QALYs gained per 100,000 women. The model was sensitive to six variables: the probability of uterine rupture and successful TOLAC among women with no prior vaginal delivery, the frequency of stress urinary incontinence, and the costs of failed TOLAC, successful TOLAC, and ERCD. When the probability of TOLAC success was at the base value, 67.2%, TOLAC was preferred if the probability of uterine rupture was 3.1% or less. When the probability of uterine rupture was at the base value, 0.8%, the TOLAC strategy was preferred as long as the probability of success was 47.2% or more. Probabilistic sensitivity analysis confirmed the base-case analysis., Conclusions: Under baseline circumstances, TOLAC is less expensive and more effective than an ERCD when considering long-term consequences when the likelihood of success is 47.2% or more., (Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.)

Seizures during pregnancy complicate <1% of all gestations; however, they are associated with increased adverse maternal and perinatal outcomes (acute and long term). The differential diagnosis of seizures in pregnancy is extensive. Determining the underlying etiology is crucial in the management of these patients. Medical providers caring for pregnant women should be educated about possible etiologies of seizures during pregnancy and the importance of prompt management of these women in a timely fashion. Evaluation and management should be performed in a stepwise fashion and may require a multidisciplinary approach with other specialties such as neurology. The objective of this review is to increase awareness and to provide a stepwise approach toward the diagnosis and management of pregnancies complicated by seizures., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To report maternal and perinatal outcomes in obstetric patients with severe sepsis and septic shock., Methods: We performed a retrospective study of obstetric patients admitted to an intensive care unit (ICU) for severe sepsis/septic shock. Maternal clinical characteristics, hemodynamic profiles, laboratory findings, and perinatal outcomes were evaluated. Patients with severe sepsis (N = 20) and septic shock (N = 10) were compared using Fisher's Exact and Mann-Whitney U tests., Results: Pyelonephritis was the most common etiology overall (37%) and acute respiratory distress syndrome (ARDS) was the most common organ injury in both severe sepsis (50%) and septic shock (80%). Liver dysfunction was present in cases with increased morbidity as a late finding and was the least frequent organ injury. Patients with septic shock had significantly higher rates of disseminated intravascular coagulation (DIC) (p = 0.01), altered mental status (p ≤ 0.001), total bilirubin >4 mg/dl (p = 0.04), failure in ≥3 organ systems (70% vs. 15%, p = 0.005), and maternal death (30% vs. 0%, p = 0.03). All patients with septic shock were delivered during hospitalization vs. 40% with severe sepsis. 71% of viable pregnancies required emergent cesarean delivery, and 50% of these for worsening respiratory function., Conclusions: ARDS is frequently found in critically ill obstetric patients with severe sepsis/septic shock and is associated with a high risk of emergent cesarean delivery.

Objective: To evaluate whether neonates born to women who previously had received antenatal corticosteroids and then delivered a late-preterm-birth neonate had less respiratory morbidity compared with those not exposed to antenatal corticosteroids., Methods: This is a secondary analysis from a multicenter observational study regarding mode of delivery after previous cesarean delivery. We compared women who received one course of antenatal corticosteroids with unexposed parturients and evaluated various respiratory outcomes among those having a singleton, late-preterm-birth neonate. We controlled for potential confounders including gestational age at delivery, diabetes, mode of delivery, and maternal race., Results: Five thousand nine hundred twenty-four patients met the inclusion criteria; 550 received steroids and 5,374 did not. In the univariable model, compared with unexposed women, those who received antenatal corticosteroids appeared more likely to have neonates who required ventilatory support (11.5% compared with 8.6%, P=.022), had respiratory distress syndrome (RDS) (17.1% compared with 12.2%, P=.001), developed transient tachypnea of the newborn (12.9% compared with 9.8%, P=.020), or required resuscitation in the delivery room (55.8% compared with 49.7%, P=.007). After controlling for confounding factors, we found no significant differences among the groups regarding all of the above outcomes with an odds ratio for RDS of 0.78 (95% confidence interval, 0.60-1.02) and ventilator support of 0.75 (95% confidence interval, 0.55-1.03)., Conclusion: Exposure to antenatal corticosteroids does not significantly affect respiratory outcomes among those with a subsequent late-preterm birth.

Objective: The purpose of this study is to assess the incidence of clinically significant neonatal abstinence syndrome (NAS) based on maternal antenatal methadone dosing in women with a history of narcotic dependence., Study Design: A retrospective review of 174 pregnant women on methadone maintenance was performed. Data were stratified based on maternal methadone dose at delivery: low (0-50 mg/day, n = 59), medium (51-100 mg/day, n = 63), and high (>100 mg/day, n = 52). NAS was defined by Finnegan as score greater than 7 on two occasions. Outcome measures were rate and severity of NAS, birth weight, preterm birth rate, and neonatal morbidities and mortality., Results: The rates of NAS (40.7% vs. 52.4% vs. 40.8%, p > .05), birth weight, and neonatal morbidities were similar regardless of the maternal methadone dose. Although there was a trend toward earlier delivery, the rate of preterm birth among the three groups (low dose, 17%; medium dose, 19%; high dose, 27%; p > .05) was not statistically significant., Conclusion: Higher maintenance dosing of methadone is not associated with increased rate or severity of NAS or other adverse perinatal outcomes. Concerns about NAS should not restrict the methadone dosing during pregnancy. Methadone dosing should not be restricted to lower dosing during pregnancy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To assess whether functional maternal or fetal genotypes along well-characterized metabolic pathways (ie, CYP1A1, GSTT1, and CYP2A6) may account for varying associations with adverse outcomes among pregnant women who smoke., Methods: DNA samples from 502 smokers and their conceptuses, alongside women in a control group, were genotyped for known functional allelic variants of CYP1A1 (Ile462Val AA>AG/GG), GSTT1(del), and CYP2A6 (Lys160His T>A). Modification of the association between smoking and outcome by genotype was evaluated. Outcomes included birth weight, pregnancy loss, preterm birth, small for gestational age, and a composite outcome composed of the latter four components plus abruption., Results: No interaction between maternal or fetal genotype of any of the polymorphisms and smoking could be demonstrated. In contrast, the association of smoking with gestational age-adjusted birth weight (birth weight ratio) was modified by fetal GSTT1 genotype (P for interaction=.02). Fetuses with GSTT1(del) had a mean birth weight reduction among smokers of 262 g (P=.01), whereas in fetuses without the GSTT1(del) the effect of tobacco exposure was nonsignificant (mean reduction 87 g, P=.16). After adjusting for confounding, results were similar., Conclusion: Fetal GSTT1 deletion significantly and specifically modifies the effect of smoking on gestational age-corrected birth weight.

Objective: To estimate whether maternal carriage of the prothrombin gene G20210A mutation is associated with pregnancy loss, preeclampsia, placental abruption, or small for gestational age (SGA) neonates in a low-risk, prospective cohort., Methods: This was a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development factor V Leiden study, a multicenter, prospective, observational cohort of 5,188 unselected singleton gestations. A total of 4,167 first-trimester samples were available for analysis and were tested for the prothrombin G20210A mutation. Obstetric complications were compared between women with and without the prothrombin G20210A mutation by univariable and multivariable analysis., Results: A total of 157 (3.8%) women had the prothrombin gene mutation (156 heterozygous and one homozygous). Carriers of the prothrombin G20210A mutation had similar rates of pregnancy loss, preeclampsia, SGA neonates, and abruption compared with noncarriers. Results were similar in a multivariable analysis controlling for age, race, prior pregnancy loss, prior SGA neonates, and family history of thromboembolism. Three thromboembolic events occurred in women testing negative for the mutation., Conclusion: There was no association between the prothrombin G20210A mutation and pregnancy loss, preeclampsia, abruption, or SGA neonates in a low-risk, prospective cohort. These data raise questions about the practice of screening women without a history of thrombosis or adverse pregnancy outcomes for this mutation., Level of Evidence: II.

Objective: The objective of the study was to evaluate the indications for late preterm birth and compare outcomes by gestational age among late preterm (34-36 weeks) and term (> or = 37 weeks) neonates at our institution., Study Design: This was a retrospective analysis of delivery indications and short-term neonatal outcomes in women who delivered at the University Hospital between January 1, 2005 and Dec. 31, 2006. Data were analyzed using chi(2), Student's t-test, analysis of variance, and post hoc Tukey tests., Results: One hundred forty-nine late preterm (n = 49 for 34, n = 50 for 35, n = 50 for 36 weeks) and 150 term infants (n = 50 for 37, n = 50 for 38, n = 50 for 39 weeks or longer) were evaluated. Differences among groups (ie, 34 vs 35 vs 36 vs 37, etc) as well as combinations of differences between 2 groups (ie, 34-36 weeks vs > or = 37 or > or = 38 weeks) were analyzed. Spontaneous labor and/or rupture of membranes were the most common indications for late preterm delivery (92%). Compared with term, late preterm infants had longer hospital stays (5 days vs 2.4 days; P < .001) and higher rates of neonatal intensive care unit (NICU) admissions (56% vs 4%; P < .001), feeding problems (36% vs 5%; P < .001), hyperbilirubinemia (25% vs 3%; P < .001), and respiratory complications (20% vs 5%; P < .001). Neonatal complications were minimal at 38 weeks or longer., Conclusion: Rates of neonatal intensive care unit admission, length of stay, and neonatal morbidities are significantly higher in late preterm as compared with term births.

Objective: To assess the associations among maternal obesity, uterine contraction frequency, and spontaneous preterm birth in women at risk for spontaneous preterm birth., Methods: In a secondary analysis, we analyzed data from 253 women at risk for spontaneous preterm birth (prior spontaneous preterm birth, vaginal bleeding) enrolled in a multicenter observational study of home uterine activity monitoring at 11 centers. All women wore a uterine activity monitor twice daily from 22 weeks through 34 weeks of gestation. Mean and maximal contractions/hour at 22-24, 25-26, 27-28, 29-30, 31-32 weeks, and at or after 33 weeks of gestation were compared between overweight/obese women (a body mass index [BMI] at 22-24 weeks greater than 25 kg/m) and normal/underweight women (a BMI of 25 kg/m or less) at each gestational age interval. Multivariable analysis evaluated the influences of BMI, contractions, fetal fibronectin, and transvaginal cervical length on spontaneous preterm birth before 35 weeks., Results: Obese/overweight women (n=156) were significantly less likely to experience spontaneous preterm birth before 35 weeks (8.3% compared with 21.7%, P<.01). For each gestational age interval before 32 weeks, obese/overweight women had fewer mean contractions/hour (P<.01 for each) and maximal contractions/hour (P<.01 for each) than normal/underweight women, although their mean cervical lengths (34.3 mm compared with 33.1 mm, P=.25), and fetal fibronectin levels (7.1% compared with 7.2% 50 ng/mL or more, P=.97) were similar at study enrollment. Obese/overweight status was associated with a lower risk of spontaneous preterm birth before 35 weeks after controlling for contraction frequency and other factors evaluated at 22-24 weeks, but not at later periods., Conclusion: Obese/overweight women at risk for spontaneous preterm birth exhibit less uterine activity and less frequent spontaneous preterm birth before 35 weeks of gestation than normal/underweight women., Level of Evidence: II.

Objective: To estimate success rates and risks with a trial of labor after one previous cesarean delivery for multifetal gestation compared with one previous cesarean delivery for a singleton pregnancy., Methods: Patients from the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network Cesarean Registry with one previous cesarean delivery and a current term singleton pregnancy were identified. Cases had one previous cesarean delivery for a multifetal pregnancy. Controls had one previous cesarean delivery for a singleton pregnancy., Results: Of cases, 556 of 944 (58.9%) attempted a trial of labor. Of controls, 13,923 of 29,329 (47.5%) attempted a trial of labor. The trial of labor success rate was 85.6% among cases and 73.1% among controls (odds ratio 2.19, 95% confidence interval 1.72-2.78). Compared with trial of labor controls, cases had no statistically increased risk of transfusion, endometritis, intensive care unit admissions, uterine rupture, or perinatal complications. Cases in this analysis with a successful trial of labor were more likely to have previously had a successful vaginal birth after cesarean (37.1% compared with 14.1%, P<.001)., Conclusion: Women with one previous cesarean delivery for a multifetal gestation have high trial of labor success rates and low complication rates.

Background: Mirror syndrome is a rare entity characterized by maternal disease mimicking fetal hydrops. In mirror syndrome, there is maternal hypertension, edema, and often proteinuria in association with fetal hydrops. The causal link between mirror syndrome and hydrops fetalis remains elusive., Case: This is a case report of a pregnant woman who developed mirror syndrome associated with fetal hydrops. A fetal pelvic mass resulted in bladder outlet obstruction, subsequent bladder rupture, and massive urinary ascites. The resultant massive ascites caused thoracic and cardiac compression and subsequent hydrops fetalis. Placement of a peritoneal-amniotic shunt resolved the fetal hydrops and maternal mirror syndrome., Conclusion: In utero treatment of hydropic fetus can result in the cure of maternal mirror syndrome.

Objective: Assess effects of body mass index (BMI) on trial of labor after previous cesarean delivery and determine whether morbidly obese women have greater maternal and perinatal morbidity with trial of labor compared with elective repeat cesarean delivery., Methods: Secondary analysis from a prospective observational study included all term singletons undergoing trial of labor after previous cesarean delivery. Body mass index groups were as follows: normal 18.5-24.9, overweight 25.0-29.9, obese 30.0-39.9, morbidly obese 40.0 kg/m2 or greater, and were compared for failure and maternal and neonatal morbidities. The morbidly obese trial of labor and elective repeat cesarean delivery were compared for maternal and neonatal morbidities. Multivariable logistic regression analysis controlled for confounding variables., Results: There were 14,142 trial of labor participants and 14,304 elective repeat cesarean delivery participants. Increasing BMI was directly associated with failed trial of labor after previous cesarean delivery: from 15.2% in normal weight (1,344) to 39.3% in morbidly obese (1,638), with combined risk of rupture/dehiscence increasing from 0.9% to 2.1% in morbidly obese women. Among morbidly obese women, trial of labor carried greater than five-fold risk of uterine rupture/dehiscence (2.1% versus 0.4%), almost a two-fold increase in composite maternal morbidity (7.2% versus 3.8%) and five-fold risk of neonatal injury (1.1% versus 0.2%) (fractures, brachial plexus injuries, and lacerations), but no neonatal encephalopathy. Morbidly obese women failing a trial of labor had six-fold greater composite maternal morbidity than those undergoing a successful trial of labor (14.2% versus 2.6%)., Conclusion: Body mass index correlates with outcomes in trial of labor after previous cesarean delivery. Morbidly obese women undergoing a trial of labor were at increased risk for failure. Increased BMI was associated with greater composite morbidity and neonatal injury compared with elective repeat cesarean delivery, but absolute morbidities were small. Increased risks should be considered before trial of labor after previous cesarean delivery., Level of Evidence: II-2.

Objectives: This study was undertaken to determine the influence of increased prepregnancy body mass index (BMI) on pregnancy outcome in women with mild gestational hypertension remote from term., Study Design: A matched cohort design was used. A total of 365 pregnant women with mild gestational hypertension and a normal prepregnancy BMI (20-25 kg/m2) were matched 1:1 for gestational age at diagnosis, race and parity to 365 women with mild gestational hypertension, but an obese prepregnancy BMI (> or = 30 kg/m2)., Results: Matched characteristics were distributed as follows: gestational age at diagnosis 32.2 +/- 2.4 weeks; race 80.8% white; parity 59.7% nulliparous. The rate of progression to preeclampsia was the primary endpoint of the study and was similar between the prepregnancy normal and obese BMI groups (37.8% vs 41.1%, P = .352). Birth weight at delivery (3033 +/- 747 g vs 2833 +/- 659 g, P < .001) and cesarean delivery rate (56.7% vs 40.3%, P < .001) were greater in the obese prepregnancy BMI group., Conclusion: In patients with mild gestational hypertension remote from term, an obese prepregnancy BMI was associated with similar rates of progression to preeclampsia. Secondarily, an obese prepregnancy BMI was associated with higher birth weights and an increased incidence of cesarean delivery.

Objective: The purpose of this study was to determine the demographics, clinical presentation, and maternal and neonatal outcomes in patients who were diagnosed with acute fatty liver of pregnancy over a 10-year period., Study Design: This was a multicenter retrospective study of women with the diagnosis of acute fatty liver of pregnancy. Records were reviewed for symptoms, laboratory findings, clinical course, and maternal and perinatal outcomes., Results: Sixteen cases of acute fatty liver of pregnancy were identified. Three of the 16 cases had multiple gestations (18%). Eleven of the 16 cases were diagnosed in the antepartum period, and 5 cases were diagnosed within 4 days after delivery. Nausea and vomiting were the most common symptoms (75%). There were 2 maternal deaths (12.5%) and 3 fetal deaths (15%)., Conclusion: We recommend that patients with persistent nausea, vomiting, or epigastric pain in the third trimester receive evaluation of liver enzymes, renal function, and a complete blood count to rule out the diagnosis of acute fatty liver of pregnancy.

Several microangiopathic disorders that are encountered during pregnancy provide physicians with a formidable diagnostic challenge. Severe pre-eclampsia with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and many other obstetric and medical or surgical conditions produce similar clinical presentations and laboratory study results to pre-eclampsia. Pre-eclampsia is frequently superimposed on one of the above disorders, further confounding an already difficult differential diagnosis. Because of the remarkably similar clinical and laboratory findings of these disease processes, even the most experienced physician will face a diagnostic challenge. An effort should be made to make an accurate diagnosis, given the fact that management strategies and outcome may differ among these conditions.

Although the incidence of stroke is extremely low, the complications are serious. Maternal mortality has been reported to be as high as 26%. It is important for doctors to be aware of the causes, diagnostic techniques, and management strategies for stroke in order to achieve the best outcome for the mother and fetus. Recurrence risk appears extremely low, so women should feel confident in future positive pregnancy outcomes.

Objective: The purpose of this study was to describe current practice patterns for 7 controversial topics in Maternal-Fetal Medicine., Study Design: An interactive survey of obstetric treatment was performed as part of a postgraduate course at the 2004 Annual Meeting of the Society for Maternal-Fetal Medicine. Seven controversial topics were addressed, which included tocolytic therapy, progesterone supplementation for the prevention of preterm birth, screening for inherited thrombophilia, cervical cerclage for a shortened cervix, treatment of preterm premature rupture of membranes, magnesium sulfate seizure prophylaxis, and dexamethasone therapy for HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome., Results: A total of 298 obstetric care providers attended the postgraduate course. By report, most attendees were maternal-fetal medicine specialists (60.7% of respondents) who were >10 years out from specialty training (56.3% of respondents) and who were practicing in a university-based setting (52.9% of respondents). An average of 233 practitioners (range, 157-298 practitioners) answered each question. An analysis of the responses allowed for the determination of current practice patterns in the 7 controversial areas addressed., Conclusion: Contemporary practice patterns for 7 controversial topics in obstetric medicine are described. Such surveys may be useful in defining standards of care in maternal-fetal medicine.

Objective: Inadequate data describe pancreatitis as a complication in women with acute fatty liver of pregnancy. Our purpose was to report our experience with this complication, which included maternal and perinatal outcomes., Study Design: Medical records of patients with acute fatty liver of pregnancy and/or pancreatitis were reviewed over a 15-year period. Records were reviewed for symptoms, laboratory findings, clinical course, and maternal and perinatal outcomes., Results: Persistent nausea and vomiting were the symptoms in 10 of 12 patients (83%). The average maternal age was 26.3 years (range, 21-37 years). There were two maternal deaths (17%); one death occurred despite liver transplantation. Maternal morbidity included encephalopathy (50%), acute respiratory distress syndrome (17%), and renal failure (33%) that resulted from acute tubular necrosis (3 cases) and acute cortical necrosis (1 case) that required renal transplantation. Of the 12 patients, 11 patients (91%) had an elevated serum lipase level, and another patient had an elevated serum amylase level (9%). Eight of 12 patients (67%) underwent radiologic studies, of which 7 patients (88%) were diagnostic for pancreatitis. Radiographic and autopsy findings noted pancreatic inflammation (3 cases), pseudocyst formation (3 cases), and hemorrhagic pancreatitis (1 case). The radiographic and serum laboratory abnormalities occurred after the onset of hepatic and renal abnormalities in all cases., Conclusion: Pancreatitis is a potentially lethal complication of acute fatty liver of pregnancy, and all patients with this diagnosis should undergo screening for the abnormality. Pancreatic abnormalities typically appear after hepatic and renal dysfunction.

A 28-year-old woman admitted to the emergency department with a Glascow Coma Scale score of 4 after a closed head injury resulting from a motor vehicle crash was found to have a positive serum beta-human chorionic gonadotropin level of 27 mIU/mL. After stabilization and treatment for her closed head injury, she remained in a comatose state for more than 240 days. At 36 to 37 weeks' gestation, she had contractions and elevations in her blood pressure. A healthy female infant was born by an operative vaginal delivery with Apgar scores of 9 and 9.

Objective: Our purpose was to determine the risk of preeclampsia and gestational hypertension among nulliparous pregnant women with idiopathic hematuria., Study Design: We conducted a prospective cohort study using data from the trial of Calcium for Preeclampsia Prevention (CPEP). Participants were followed up from screening and enrollment (gestational weeks 11-21) throughout pregnancy. Our analysis was limited to women who had been followed up to at least 20 weeks' gestation, had outcome information available, and were not suspected to have had urolithiasis. Surveillance for hematuria was conducted with dipsticks on clean-catch urine specimens obtained at research clinic visits. Idiopathic hematuria was defined as hematuria identified at regularly scheduled clinic visits in the absence of urinary tract infection and before the onset of labor. Logistic regression was used to estimate the risk of preeclampsia among women with hematuria compared with women without hematuria., Results: Among the 4307 women available for analysis, 132 (3%) had idiopathic hematuria during pregnancy. Idiopathic hematuria was associated with an almost 2-fold increased odds for development of preeclampsia (adjusted odds ratio [aOR] = 1.89, 95% CI 1.12- 3.18) but not with increased odds of gestational hypertension (aOR = 0.78, 95% CI 0.46-1.32)., Conclusions: Idiopathic hematuria identified during pregnancy is associated with greater risk of preeclampsia but not gestational hypertension.

Sepsis is a life-threatening syndrome caused by the body's response to infection. The Global Maternal Sepsis Study (GLOSS) suggests sepsis plays a larger role in maternal morbidity and mortality than previously thought. We therefore sought to compare national and international guidelines for maternal sepsis to determine their consistency with each other and the Third International Consensus for Sepsis and Septic Shock (SEPSIS-3). Using Cochrane Database of Systematic Reviews, PubMed, Google Scholar, and organization Web sites, we identified seven guidelines on maternal sepsis in the English language—The American College of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, Royal Australian and New Zealand College of Obstetricians and Gynaecologists, Society of Obstetric Medicine of Australia and New Zealand, Royal College of Obstetricians and Gynaecologists, Royal College of Physicians of Ireland Institute of Obstetricians and Gynaecologists, and World Health Organization. Guidelines were reviewed to ascertain the commonality and variation, if any, in definitions of maternal sepsis, tools and criteria utilized for diagnosis, obstetric warning systems used, as well as evaluation and management of maternal sepsis. These variables were also compared with SEPSIS-3. All guidelines provided definitions consistent with a version of the SEPSIS, although the specific version utilized were varied. Clinical variables and tools employed for diagnosis of maternal sepsis were also varied. Evaluation and management of maternal sepsis and septic shock were similar. In conclusion, national and international maternal sepsis guidelines were incongruent with each other and SEPSIS-3 in diagnostic criteria and tools but similar in evaluation and management recommendations. Key Points Definitions for maternal sepsis and septic shock are varied. Maternal sepsis guidelines differ in proposed criteria and tools. Maternal sepsis guidelines have similar management recommendations. [ABSTRACT FROM AUTHOR]

Objective The international consensus on continuous glucose monitoring (CGM) recommends time in range (TIR) target of >70% for pregnant people. Our aim was to compare outcomes between pregnant people with TIR ≤ versus >70%. Study Design This study was a retrospective study of all people using CGM during pregnancy from January 2017 to May 2021 at a tertiary care center. All people with pregestational diabetes who used CGM and delivered at our center were included in the analysis. Primary neonatal outcome included any of the following: large for gestational age, neonatal intensive care unit (NICU) admission, need for intravenous (IV) glucose, or respiratory distress syndrome (RDS). Maternal outcomes included hypertensive disorders of pregnancy and delivery outcomes. Logistic regression was used to estimate unadjusted and adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results Of 78 people managed with CGM, 65 (80%) met inclusion criteria. While 33 people (50.1%) had TIR ≤70%, 32 (49.2%) had TIR >70%. People with TIR ≤70% were more likely to be younger, have a lower body mass index, and have type 1 diabetes than those with TIR >70%. After multivariable regression, there was no difference in the composite neonatal outcome between the groups (aOR: 0.56, 95% CI: 0.16–1.92). However, neonates of people with TIR ≤70% were more likely to be admitted to the NICU (p = 0.035), to receive IV glucose (p = 0.005), to have RDS (p = 0.012), and had a longer hospital stay (p = 0.012) compared with people with TIR >70%. Furthermore, people with TIR ≤70% were more likely to develop hypertensive disorders (p = 0.04) than those with TIR >70%. Conclusion In this cohort, the target of TIR >70% was reached in about one out of two people with diabetes using CGM, which correlated with a reduction in neonatal and maternal complications. Key Points Among people with diabetes, 50% reached the recommended time in range using CGM. Time in range >70% was associated with reducing the rate of some neonatal complications. Time in range ≤70% was associated with increased risk for adverse maternal outcomes. [ABSTRACT FROM AUTHOR]

Objective This study aimed to develop and evaluate a scoring system—called the Sepsis-Associated Adverse Outcomes in Pregnancy (SAAP) Score—to identify individuals with maternal infection that have composite maternal adverse outcomes (CMAO). Study Design Using the International Classification of Disease codes, we identified pregnant and postpartum (up to 6 weeks after birth) individuals admitted at our center with a primary diagnosis of infection. The primary outcome was CMAO which included any of the following: maternal intensive care unit admission, surgical intervention, vasopressor use, acute respiratory distress syndrome, pulmonary edema, mechanical ventilation, high-flow nasal cannula, disseminated intravascular coagulation, dialysis, organ failure, venous thromboembolism, or maternal death. Regularized logistic regression was used to identify variables that best discriminate CMAO status. Variables were chosen for inclusion following evaluation of statistical and clinical significance. Model performance was evaluated using area under the curve (AUC) with 95% confidence intervals (CIs), sensitivity, specificity, and predictive values. Results Of the 23,235 deliveries during the study period, 227 (0.9%) individuals met inclusion criteria and among them CMAO occurred in 39.2% (95% CI: 33.1–45.7%). The SAAP score consisted of six variables (white blood cell count, systolic blood pressure, respiratory rate, heart rate, lactic acid, and abnormal diagnostic imaging) with scores ranging from 0 to 11 and a score of ≥7 being abnormal. An abnormal SAAP score had an AUC of 0.80 (95% CI: 0.74–0.86) for CMAO. The sensitivity and specificity of the SAAP score for CMAO was 0.71 (95% CI: 0.60–0.80) and 0.73 (95% CI: 0.64–0.80), respectively. The positive predictive value was 0.62 (95% CI: 0.52–0.72) and negative predictive value was 0.79 (95% CI: 0.71–0.86). Conclusion Pending external validation, the sixth variable SAAP score may permit early recognition of pregnant and postpartum individuals with infection who are likely to develop adverse maternal outcomes. Key Points Sepsis is a leading cause of maternal morbidity and mortality. Early recognition improves maternal sepsis outcomes. The SAAP score may permit early recognition of maternal adverse outcomes due to infection. [ABSTRACT FROM AUTHOR]

Objective  To determine whether basal insulin analogs reduce the rate of composite neonatal morbidity compared with neutral protamine Hagedorn (NPH) in women with type 2 diabetes mellitus (T2DM). Study Design  This was a retrospective cohort study of women with T2DM and singleton pregnancy at a single tertiary center. Primary outcome was a composite neonatal morbidity of any of the following: shoulder dystocia, large for gestational age, neonatal intensive care unit admission, neonatal hypoglycemia, or respiratory distress syndrome. Secondary outcomes were rates of maternal hypoglycemic events, hypertensive disorders, preterm birth, and primary cesarean delivery. Adjusted relative risk (aRR) and 95% confidence intervals (CI) were calculated. Results  Of 233 women with T2DM that met the inclusion criteria, 114 (49%) were treated with basal insulin analogs and 119 (51%) with NPH. The rate of composite neonatal morbidity was similar between groups (73 vs. 60%; aRR: 1.18; 95% CI: 0.92–1.51). There were no differences in the rates of maternal adverse outcomes between the groups. Basal insulin analog was associated with a lower rate of primary cesarean delivery as compared with NPH (21 vs. 36%; aRR: 0.44; 95% CI: 0.25–0.78). Conclusion  Among pregnant women with T2DM managed with either basal or NPH insulin regimen, the rates of composite neonatal morbidity and maternal complications were similar. [ABSTRACT FROM AUTHOR]

Purpose: Our goal was to compare composite neonatal and maternal morbidities (composite neonatal morbidity (CNM), composite maternal morbidity (CMM)) among deliveries with small for age (SGA) versus appropriate for gestational age (AGA; birthweight 10-89%) among obese versus non-obese women undergoing repeat cesarean delivery (CD).Study Design: This is a secondary analysis of a prospective observational study. Women who had elective CD ≥37 weeks were studied. We excluded multiple gestations, fetal anomalies, > 1 prior CD, and medical diseases. Patients were divided into BMI ≥30 versus <30 kg/m2. CNM included respiratory distress syndrome, necrotizing enterocolitis, severe intraventricular hemorrhage, seizure, or death; CMM included transfusion, hysterectomy, operative injury, coagulopathy, thromboembolism, pulmonary edema, or death. Multivariate logistic regression was used to control for confounding factors.Results: Of 7561 women, we included 65% were obese and 35% were not. SGA rates differed significantly: 8 versus 12% (p < .001). Overall, CNM was significantly higher in patients with SGA versus AGA (adjusted odds ratio (aOR) 2.04, 95% CI 1.19-3.49). CMM of SGA in obese versus non-obese was statistically different (aOR 0.11, 95% CI 0.02-0.68). Among obese mothers, SGA neonates had significantly higher CNM compared with AGA ones (aOR 2.17, 95% CI 1.03-4.59).Conclusions: SGA occurred in 8% of low-risk obese women with prior CD. CNM of SGA babies in obese versus non-obese women were similar. Paradoxically, CMM was lower in obese cases, possibly reflecting the caution that obese patients receive preoperatively. Our findings may assist in counseling patients and designing trials. [ABSTRACT FROM AUTHOR]

We performed a systematic review to evaluate the clinical presentation and maternal and fetal outcomes in pregnancies with early-onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. PubMed, Ovid MEDLINE, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov were queried from inception through January 1, 2023 with the following terms: "HELLP syndrome," "HELLP," "hemolysis, elevated liver enzymes, low platelets," "hemolysis, elevated liver enzymes, low platelets syndrome," "pre-viable," "peri-viable," "previable," "periviable," "first trimester," "second trimester," "before 23 weeks," "<23 weeks," "<23 week gestation," and "before 23 weeks gestation." We also included an additional case from our institution. Abstracts, unpublished studies, and review articles were excluded, yielding 46 studies that met our inclusion criteria. Two reviewers (N.S.I. and M.H.M.) performed the study selection and subsequent data extraction independently, after which the results were reviewed together. PRISMA guidelines were followed, and our study was registered at PROSPERO (CRD42021292692). A total of 55 patients had 58 pregnancies complicated by early-onset HELLP syndrome, including 3 with recurrent HELLP. The most common presenting signs/symptoms were abdominal pain (35/45; 78%), hypertension (32/49; 65%), nausea/vomiting (16/45; 36%), headache (13/45; 29%), and edema (8/45; 18%). Lactate dehydrogenase ≥600 IU/L was observed in 21 of 31 (68%) cases, whereas liver enzyme abnormalities and thrombocytopenia were reported in 48 of 51 (94%) and 50 of 54 (93%) cases, respectively. Maternal complications were encountered in 25 of 56 (45%) cases. The most common complications were hepatic (13/56; 23%), central nervous system–related (11/56; 20%), and respiratory (11/56; 20%). In 36 of 57 (63%) cases, pregnancy was terminated. Of the 21 continued pregnancies, early fetal death (at <20 weeks' gestation) was reported in 10 (48%), stillbirth in 6 (28%), and neonatal demise in 2 (10%). Living neonates were reported in 3 of 21 (14%) cases, all delivered at 23 weeks. The perinatal mortality rate was 73% (8/11). One case (2%) reported maternal death. Antiphospholipid syndrome was diagnosed in 14 of 29 (48%) cases. Early-onset HELLP syndrome presents with symptoms similar to those observed in later gestation. Maternal complications are life-threatening, with the most common complications being hepatic, central nervous system–related, and respiratory. Fetal outcomes are poor. [Display omitted] [ABSTRACT FROM AUTHOR]