Yr Postpartum Research Articles

FRI343 A Case Of Postpartum Adrenal Crisis Secondary To Empty Sella

Abstract Disclosure: A. Alzenaidi: None. Empty sella occurs when the pituitary gland appears shrunken or invisible and CSF fills the sella turcica space. It is commonly defined in the radiology literature as an incidental finding of no clinical significance, but an association with sequalae of lymphocytic hypophysitis (LH) was observed in a mouse model of the disease. However, patient data on the development of empty sella are scant and present later in life.To our knowledge, this is the second case of postpartum empty sella with clinically suspected LH and early presentation within 2 yr postpartum. A 31-year-old woman presented to our endocrine clinic for pituitary evaluation. She was 16 months post-spontaneous vaginal delivery with no history of excessive bleeding or blood transfusion. Her pregnancy was uneventful except for headache without visual changes after the thirty-fifth week, which improved with nasal steroid spray. Four to six weeks postpartum, she presented to her primary care physician with palpitations, fatigue and weight loss. Labs showed TSH, 0.001 mIU/mL (0.3-4.2); free T4, 30.98 pmol/L (9-19); free T3, 23.04 pmol/L (2.6-5.7); and thyroid peroxidase antibodies, 512.6 IU/mL (<5.6). Thyroid function tests improved after a short course of carbimazole, although without significant improvement of her symptoms. At 10 months postpartum, she presented to the ED with worsening fatigue, weight loss, vomiting and dizziness. Further history revealed oligomenorrhea and an inability to lactate since delivery. On exam, her heart rate was 100 b/m, respiratory rate was 20 b/m, BP was 90/50 mmHg, and temperature was 38.8 C. Labs showed WBC, 4.26 x 103/µL (4-11); Hb, 9.9 g/dL (11.8-14.8); PLT, 181 x 103/µL (150-450); Na, 136 mEq/L (135-145); K, 3.6 mEq/L (3.5-5.1); HCO3, 20 mmol/L (22-29); creatinine, 62 µmol/L (49-90); lactate, 0.82 mmol/L (0.5-2.2); FSH, 6.16 IU/L; prolactin, < 12.6 mIU/L (110-564) (prolactin prepregnancy was 233 mIU/L); TSH, 6.7 (0.3-4.2); free T4, <5.15 pmol/L (9-19); ACTH, 0.22 pmol/L (1.03-10.73); cortisol, 50.3 nmol/L (1.82 µg/dl); and peak cortisol after 250 mcg ACTH stimulation test, 223.5 nmol/L (8.1 µg/dl). She was treated with intravenous fluids and hydrocortisone. Pituitary MRI showed marked compression of the pituitary tissue with concave superior margins due to partially empty sella. She was maintained only on hydrocortisone replacement. During follow-up, her menstrual cycle resumed regularly, and fatigue and thyroid function improved (TSH, 2.65 µIU/ml; free T4, 12.13 pmol/L). Our patient had autoimmune thyroiditis with positive TPO antibodies, and it is possible that she had coexistent LH. LH typically presents as a pituitary mass; however, our patient had empty sella.In conclusion, the development of empty sella in this case suggests that postpartum atrophy of the pituitary gland can be life threatening if associated with hypopituitarism. Early recognition could prevent serious consequences. Presentation: Friday, June 16, 2023

Impact of pregnancy in women with desmoid fibromatosis: An international retrospective observational study.

11513 Background: Desmoid fibromatosis (DF) often occurs during pregnancy/peripartum. Guidance for planning new pregnancies during active surveillance or following DF resection has been limited. Thus, we sought to evaluate outcomes and decision making in the peripartum. Methods: Women of child-bearing age with DF diagnosed between 2000 and 2020 were interviewed about procreation decisions, in a multicenter retrospective observational study (NCT05284305). Pregnancies simultaneous or after diagnosis were analyzed. Primary outcome was DF progression/recurrence within 1 yr postpartum. Secondary outcomes were spontaneous regression, switch to active treatment, and obstetric risks. To estimate probability of progression, a random intercept logistic model was fit to account for correlation of progression in multiple pregnancies in the same patient. Results: Of 483 pts interviewed, 120 (24.8%) postponed, 32 (6.6%) interrupted, and/or 232 (48%) avoided pregnancy (in 93.3%, 50%, and 72.9% of cases because of DF), respectively. 147 pregnancies in 131 pts were concurrent with or after diagnosis: 26 (17.7%, Group A) concurrent with diagnosis, 48 (32.7%, B) after DF resection, and 73 (49.7%, C) with DF on surveillance. Estimated probability of progression was 12.0% (CI 2.0 – 48.4) during pregnancy and 15.8% (5.6 – 37.5) postpartum; for pregnancies after diagnosis (Groups B and C), these rates were 5.1% (0.4 – 40.0) and 9.0% (1.8 – 35.0). On multivariate analysis, age at pregnancy and size of primary DF were significant risk factors for progression (Table). Estimated probability of spontaneous regression was 3.6% (CI 0.2-40.7) during pregnancy and 7.1% (CI 0.3 – 67.2) postpartum. 7/38 (18.4%) spontaneously regressed after pregnancy-related PD, 4/23 (17.4%) in Groups B and C. Treatment for progression was needed in 9/79 (11.4%) postpartum, in 4/63 (6.3%) in Groups B and C. Obstetric complications were comparable to population data in developed countries. Conclusions: After DF diagnosis, pregnancy is safe with a risk of progression of 5% during pregnancy and 9% postpartum. Treatment is needed in only 6%. Spontaneous regression is less common but occurs even after initial progression. Patients decision making about procreation appeared to be influenced by their DF diagnosis. This study supports counseling that fertility options should be fully explored with expert guidance as intervention rates are low. [Table: see text]

Body Growth and Rapid Hematological Development Support Breath Hold of Baby Belugas (Delphinapterus leucas) during Subice Transit.

Body size and oxygen stores in the blood and muscle set breath-hold limits in marine mammals, yet these characteristics are understudied in immature cetaceans. We examined body mass and hematology from birth through adulthood in beluga whales (Delphinapterus leucas). At birth, body mass was 8% and 6% of the maximum mass recorded for adult females and males, respectively. Body mass then increased rapidly, approaching an asymptote around 12 yr for females and 18 yr for males. Interestingly, red blood cell counts, hemoglobin content, and hematocrit levels decreased after birth; this neonatal anemia was reversed as levels increased after 2 mo postpartum. Mature levels were obtained at approximately 8, 9, and 11 mo postpartum, respectively. Neonatal mean corpuscular hemoglobin also increased with ontogeny; mature levels were achieved by approximately 13 mo after birth. In contrast, mean corpuscular volume and mean corpuscular hemoglobin concentration demonstrated a significant but subtle increase throughout ontogeny. Our results indicate that postnatal maturation was required and that maturation occurred far earlier than the age at weaning (i.e., 2-3 yr postpartum). This is atypical of marine mammals, which generally achieve mature hemoglobin levels at weaning. Hematological maturation before maternal independence undoubtedly supports the prolonged breath holds of young belugas transiting under sea ice. This assessment enhances our knowledge of cetacean physiology and provides important inputs for determining age-specific dive capacity, yielding insights into age-specific flexibility to alter underwater behaviors, as will be required for future regime shifts and disturbances.

Prior lactation reduces future diabetic risk through sustained postweaning effects on insulin sensitivity.

Breastfeeding for ≥12 mo is recommended for optimal infant nutrition but may hold maternal benefits as well. Indeed, lactation has been associated with lower long-term risk of diabetes in the mother, but the mechanism by which it imparts sustained postweaning effects on glucose tolerance remains unclear. In this context, we postulated that lactation could potentially induce postweaning beneficial effects on glucose tolerance by modifying the natural history of insulin sensitivity and/or pancreatic β-cell function over time. Thus, in this study, we evaluated the relationships between duration of lactation [≤3 mo (n = 70), 3-12 mo (n = 140), and ≥12 mo (n = 120)] and trajectories of insulin sensitivity/resistance, β-cell function, and glycemia over the first 3 yr postpartum in a cohort of 330 women comprising the full spectrum of glucose tolerance in pregnancy, who underwent serial metabolic characterization, including oral glucose tolerance tests, at 3 mo, 1 yr, and 3 yr postpartum. The prevalence of dysglycemia (pre-diabetes/diabetes) at 3 yr postpartum was lower in women who breastfed for ≥12 mo (12.5%) than in those who breastfed for ≤3 mo (21.4%) or for 3-12 mo (25.7%)(overall P = 0.028). On logistic regression analysis, lactation for ≥12 mo independently predicted a lower likelihood of prediabetes/diabetes at 3 yr postpartum (OR = 0.37, 95% CI 0.18-0.78, P = 0.009). Notably, lactation for ≥12 mo predicted lesser worsening of insulin sensitivity/resistance (P < 0.0001), fasting glucose (P < 0.0001), and 2-h glucose (P = 0.011) over 3 yr compared with lactation ≤3 mo but no differences in β-cell function (P ≥ 0.37). It has thus emerged that adherence to current breastfeeding recommendations reduces future diabetic risk through sustained postweaning effects on insulin sensitivity/resistance but not β-cell function.

Artery wall layer dimensions during normal pregnancy: a longitudinal study using noninvasive high-frequency ultrasound

The vascular effects of normal pregnancy were investigated by estimating the intima and media thicknesses of the common carotid artery separately using 22-MHz ultrasound (Collagenoson, Meudt, Germany) in 57 healthy women with normal pregnancies and pregnancy outcomes, in all three trimesters and at 1 yr postpartum. A thick intima, thin media, and high intima-to-media (I/M) ratio are signs of a less healthy artery wall. Mean artery wall layer dimensions remained fairly constant during pregnancy, but the intima thickness and I/M thickness ratio appeared to improve (decrease) postpartum (P < 0.001 for both). The cardiovascular risk parameters of age, body mass index, and blood pressure in the first trimester were associated with higher I/M ratios, especially in the second trimester, whereas higher serum estradiol levels were significantly associated with a lower I/M ratio. Changes from the first to second trimesters in I/M ratio, taking into account differential changes in intima and media thickness, were significantly (P < 0.05-0.001) associated with all risk parameters tested except age, which was associated with increased intima thickness (P = 0.02). Associations with third trimester values and changes from first to third trimesters were similar but less apparent. Thus, fairly constant mean artery wall layer dimensions during pregnancy appeared to improve postpartum. However, higher age, body mass index, or blood pressure and lower serum estradiol levels in the first trimester appeared to negatively affect the artery wall, strongly suggesting that pregnancy has negative vascular effects in some women. A less likely explanation involves possible adaptation to physiological changes during and after pregnancy.

Elevated Corticotropin Releasing Hormone (CRH) during Pregnancy and Risk of Postpartum Depression (PPD)

Perinatal depression has a prevalence of 10% with devastating consequences for mother and baby. The prospective identification of those at risk for postpartum (PPD) or prenatal (PND) depression has led to biomarker searches in pregnancy. There are conflicting reports of associations between midpregnancy placental CRH (pCRH) and PPD or PND. The objective of the study was to quantify the association of maternal pCRH with PPD and PND. This was a prospective cohort study (the Pregnancy, Infection, and Nutrition Study). The study was conducted at a prenatal clinics at the University of North Carolina at Chapel Hill. Patients included 1230 pregnant women. The relationship between pCRH at less than 20 wk and 24-29 wk and maternal depression assessed in pregnancy [Center for Epidemiologic Studies Depression Scale (CES-D)] and postpartum (12 wk and 1 yr) with the Edinburgh Postnatal Depression Scale (EPDS). At 24-29 wk, 24.8% of women had CES-D score of 17 or greater, and 9.7% had a CES-D score of 25 or greater. At 12 wk postpartum, 18.2% of women had an EPDS score of 10 or greater and 7.6% had an EPDS score of 13 or greater. CRH measures at less than 20 wk and 24-29 wk were inversely correlated with a CES-D score at 24-29 wk (n = 1080, P < 0.05 and P < 0.01, respectively). Pregnancy pCRH was not correlated with the EPDS score at 12 wk (n = 484) or 1 yr postpartum (n = 391). In covariate-adjusted models, higher pCRH was not associated with a CES-D of 17 or greater at 24-29 wk (odds ratio 0.88 per sd change in pCRH at 24-29 wk, 95% confidence interval 0.76-1.03). There was no association between log CRH at 24-29 wk and PPD (covariate-adjusted odds ratio per sd 0.99, 95% confidence interval 0.69-1.42). Higher midpregnancy pCRH was not associated with an increased risk of PND or PPD.

Gastroesophageal Reflux Symptoms During and After Pregnancy: A Longitudinal Study

Prevalence of gastroesophageal reflux symptoms (GERS) increases during pregnancy, but there are no longitudinal studies on western populations examining their incidence in each trimester. Our aim was to describe the natural history of GERS in pregnancy and to ascertain whether pregnancy might be associated with a higher risk of developing GERS 1 yr postpartum. Pregnant women (<12 wk gestation) and age-matched controls were included. A telephone survey was conducted, covering pregnant women at 12, 24, and 36 wk of gestation and at 1 yr postpartum, using a validated questionnaire. Controls were interviewed at baseline and 21 months later. Data on 263 pregnant women were analyzed. Incidence of GERS was 25.8% (95% confidence interval [CI] 20.1-31.1%) in the first trimester, 24.3% (95% CI 18.1-30.6%) in the second, and 25.5% (95% CI 18.2-32.8%) in the third. Factors associated with developing GERS in the first trimester were South American origin (odds ratio [OR] 2.75, 95% CI 1.30-5.84) and prepregnancy occasional GERS (OR 3.00, 95% CI 1.35-6.66). Risk factors of GERS in the third trimester were cumulative weight gain during pregnancy (OR 1.18, 95% CI 1.04-1.32) and prepregnancy occasional GERS (OR 3.79, 95% CI 1.08-13.24). Incidence of frequent GERS at 1 yr postpartum was higher in pregnant versus control women (4.7%vs 1.3%, P < 0.05). Incidence of GERS is similar across the three trimesters of pregnancy. Accumulated weight gain during pregnancy is associated with a higher risk of GERS in the third trimester. Pregnancy might constitute a risk factor for developing GERS 1 yr postpartum.

PHYSIOLOGICAL AND BEHAVIORAL DEVELOPMENT IN DELPHINID CALVES: IMPLICATIONS FOR CALF SEPARATION AND MORTALITY DUE TO TUNA PURSE‐SEINE SETS

AbstractTuna purse‐seiners in the eastern tropical Pacific (ETP) capture yellowfin tuna by chasing and encircling herds of associated dolphins. This fishery has caused mortality in 14 dolphin species (20 stocks) and has led to significant depletions of at least three stocks. Although observed dolphin mortality is currently low, set frequency remains high and dolphin stocks are not recovering at expected rates. Mortality of nursing calves permanently separated from their mothers during fishery operations may be an important factor in the lack of population recovery, based on the recent discovery that calves do not accompany 75%–95% of lactating females killed in the purse‐seine nets. We assessed age‐specific potential for mother–calf separations and subsequent mortality of calves by reviewing and synthesizing published data on physiological and behavioral development in delphinids from birth through 3 yr postpartum. Results indicate that evasive behavior of mothers, coupled with the developmental state of calves, provides a plausible mechanism for set‐related mother–calf separations and subsequent mortality of calves. Potential for set‐related separation and subsequent mortality is highest for 0–12‐mo‐old dolphins and becomes progressively lower with age as immature dolphins approach adult stamina and attain independence.

Risk Factors for Gallstone-Related Hospitalization During Pregnancy and the Postpartum.

Gallbladder disease is a leading nonobstetrical cause for hospitalization in the first year postpartum. The aim of this study was to define the incidence and risk factors for postpartum hospitalization as a result of gallstone-related disease. We identified 6,670 women with discharge diagnoses related to biliary disease from linked birth certificate and hospital discharge databases for Washington State from 1987 through 2001. Cases were women with gallstone-related diagnoses at delivery or as primary diagnosis in the postpartum. Four controls who were within 1 yr postpartum were randomly selected for each case and matched for year of delivery. From the birth certificates, we obtained data about patient demographics, reproductive history, and pregnancy-related risk factors. In a retrospective case-control study, we developed multiple logistic regression models to identify independent risk factors for hospitalization. We identified 6,211 women as cases (0.5% of all births) during the study period. The median time to hospitalization was 95 days (interquartile range 46-191 days), with a median length of stay of 3 days. Seventy-six percent were diagnosed with uncomplicated cholelithiasis, 16% with pancreatitis, 9% with acute cholecystitis, and 8% with cholangitis. Seventy-three percent of hospitalized women underwent cholecystectomy, and 5% underwent endoscopic retrograde cholangiopancreatography (ERCP). On multivariate analysis, independent risk factors for hospitalization included maternal race, age, being overweight or obese prepregnancy, pregnancy weight gain, and estimated gestational age. Hospitalization for gallstone-related disease is common in the first year postpartum, most commonly for uncomplicated cholelithiasis. Risk factors for hospitalization include prepregnancy body mass index, race, Hispanic ethnicity, and maternal age.

Preeclampsia and Future Cardiovascular Disease: Potential Role of Altered Angiogenesis and Insulin Resistance

Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 +/- 9.7 months postpartum. The homeostasis model of insulin resistance (HOMA(IR)) [(insulin [microunits per milliliter] x glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 +/- 6.7 vs. 30.4 +/- 10.2; P < 0.01) and median HOMA(IR) (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMA(IR) was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMA(IR) had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMA(IR) more than 1 yr postpartum. These factors may contribute to their risk of future CVD.

Reversal of insulin resistance postpartum is linked to enhanced skeletal muscle insulin signaling.

The restoration of maternal insulin sensitivity postpartum represents an important physiological and metabolic adaptation in a woman's reproductive lifespan. The present study was conducted to examine the potential cellular mechanisms underlying the changes in insulin sensitivity from late pregnancy to postpartum in human skeletal muscle. Nine nonobese women (age, 32 +/- 2 yr; body mass index, 21.2 +/- 0.8 kg/m(2)) with normal glucose tolerance were studied during late pregnancy (30-36 wk) and again approximately 1 yr postpartum using a euglycemic-hyperinsulinemic clamp (5 mm glucose, 40 mU/m(2).min insulin) to determine insulin sensitivity. Biopsies of the vastus lateralis muscle were obtained in the basal state before each clamp. Insulin sensitivity improved by 74% from late pregnancy to 1 yr postpartum (5.5 +/- 0.6 vs. 9.6 +/- 0.9 mg/kg fat-free mass.min; P < 0.005). Skeletal muscle insulin receptor (IR) protein expression increased by 42% postpartum, as measured by ELISA (4.0 +/- 0.6 vs. 5.7 +/- 0.6 ng/g protein; P < 0.05) and by Western blotting of the IR beta-subunit (28.7 +/- 4.7 vs. 42.0 +/- 4.8 arbitrary units; P < 0.003). However, in vitro studies showed that when adjusted for IR concentration, maximal insulin-stimulated (100 nm) IR tyrosine phosphorylation (0.75 +/- 0.06 vs. 0.92 +/- 0.08 U) and IR tyrosine kinase activity (183.8 +/- 27.0 vs. 204.3 +/- 23.7 fmol ATP/ng IR) were unchanged. There was a 69% increase in IR substrate-1 (IRS-1) protein expression (P = 0.05) in muscle postpartum. In addition, the p85alpha regulatory subunit of phosphatidylinositol 3-kinase was markedly reduced by 55% (P < 0.02) postpartum. The change in insulin sensitivity from late pregnancy to postpartum correlated highly with the corresponding change in IRS-1 protein (r = 0.84; P < 0.007). Downstream signaling proteins, including total Akt and p70s6 kinase, and the glucose transporter protein GLUT-4, were similar at both time points. These data suggest that reduced IR tyrosine kinase activity is not a major factor in the IR of pregnancy in lean women with normal glucose tolerance. Rather, the reversal of insulin resistance 1 yr postpartum is accompanied by increased skeletal muscle IRS-1 along with a down-regulation of the p85alpha subunit of phosphatidylinositol 3-kinase. These changes may allow for greater p85/p110 binding to IRS-1 and play a significant physiological role in the underlying metabolic adaptation to normal human pregnancy and restoration of insulin sensitivity postpartum.

Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk.

Preeclampsia is a disorder of pregnancy diagnosed by gestational hypertension and proteinuria. Epidemiological evidence suggests that women who experience preeclampsia are at a greater risk of hypertension and heart disease later in life compared with women who had normal pregnancies. Our objective was to determine whether endothelial function is impaired in postpartum women with a history of preeclampsia in their first pregnancy. We measured forearm blood flow (FBF) by venous occlusion plethysmography in 50 healthy women: 16 with prior preeclampsia, 14 with a prior normotensive pregnancy, and 20 never pregnant controls. The postpartum women participated 6-12 mo after delivery. Heart rate (HR) and blood pressure (BP) were concurrently monitored on the contralateral arm. Hemodynamic variables were assessed at baseline and during a mental stress test known to elicit endothelium-dependent vasodilatation. We found that baseline FBF, HR, systolic BP, and diastolic BP did not significantly differ among the groups, whereas mean arterial pressure in the preeclamptic group was greater than that of the normal pregnancy group (P = 0.03). Stress-induced FBF (percent change over baseline) was reduced in the preeclamptic group compared with both the normal pregnancy and never pregnant groups (P = 0.06) and was significantly attenuated compared with women with prior normal pregnancies (91% vs. 147%, P = 0.006). These data demonstrate that women with a history of preeclampsia exhibit impaired endothelial function up to 1 yr postpartum. This observation may explain their increased risk for hypertension and cardiovascular disease.

METHODOLOGY FOR CHARACTERIZING DISTRIBUTIONS OF INCREMENTAL BODY BURDENS OF 2,3,7,8-TCDD AND DDE FROM BREAST MILK IN NORTH AMERICAN NURSING INFANTS

A clear picture of ranges of doses of breast-milk contaminants experienced by nursing infants in North America has not yet been described, resulting in a significant gap in our understanding of potential health risks to infants from those contaminants. While point estimates of incremental dose have appeared in the published literature, these do not account for the wide variability in exposures experienced by nursing infants. This research expands on the current state of understanding of breast-milk contaminant exposure by characterizing distributions, rather than point estimates, of dose. Distributions of milk intake by nursing infants were characterized to exam ine intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and dichlorodiphenyl dichloroethane (DDE). The results indicate that, despite the uncertainties inherent in modeling incremental body burdens of chemicals from nursing, estimating incremental infant body burdens of lipophilic chemicals from breastfeeding using point estimates may result in overly conservative estimates of the contribution of breastfeeding to long-term body burdens of those chemicals in children. To develop reliable estimates of incremental body burden from nursing, depuration via lactation and half-life in the infant should be considered. Further, incremental infant body burdens of lipophilic chemicals increase rapidly at the start of lactation, but decrease after approximately 5 to 6 mo; by 2 yr postpartum, incremental body burdens have decreased substantially. Given the benefits afforded to infants who breastfeed, and because breastfeeding does not necessarily lead to significantly increased long-term body burdens in infants, breastfeeding should be encouraged and promoted.

Predictive value of human leukocyte antigen class II typing for the development of islet autoantibodies and insulin-dependent diabetes postpartum in women with gestational diabetes.

Gestational diabetes mellitus (GDM) is a risk factor for the development of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus postpartum. To evaluate whether there is any association of human leukocyte antigen (HLA) class II alleles (DR and DQ) with GDM and the postpartum development of IDDM, we analyzed 184 women with GDM from Germany for HLA class II alleles, islet autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A), and the postpartum development of diabetes. No elevation in the frequency of any HLA class II alleles was observed in GDM patients compared to 254 nondiabetic unrelated subjects. DR3 allele frequency was significantly increased in 43 women with islet autoantibodies [corrected P value (Pc) = 0.02], in particular in those with GADA (Pc = 0.002), or in the 24 women who developed IDDM postpartum (Pc = 0.005). In women with GADA, DR4 and DQB1*0302 were significantly elevated (Pc = 0.009). Twenty-five (59.5%) islet antibody-positive women and 17 (74%) women who developed IDDM postpartum had a DR3- or DR4-containing genotype. The cumulative risk to develop IDDM within 2 yr postpartum in GDM women with either DR3 or DR4 was 22% compared to 7% in women without those alleles (P = 0.02) and rose to 50% in the DR3- or DR4-positive women who had required insulin during pregnancy (P = 0.006). Combining the determination of susceptible HLA alleles (DR3, DR4) with islet autoantibody measurement increased the sensitivity of identifying GDM women developing postpartum IDDM to 92%, but did not improve risk assessment above that achieved using GADA measurement alone, which was the strongest predictor of IDDM. These results indicate that women with GDM who have islet autoantibodies at delivery or develop IDDM postpartum have HLA alleles typical of late-onset type 1 diabetes, and that both HLA typing and islet antibodies can predict the development of postpartum IDDM.

Maternal Age and Fawn Rearing Success for White-tailed Deer in Illinois

-Fawn survival during the 1st yr postpartum was determined for marked whitetailed does (Odocoileus virginianus) at three locations in Illinois. Fawns born to 2-yr-old does died at significantly higher annual rates (24%) than fawns born to younger (<10%) or older does (15%). Losses of fawns before weaning were not different among doe age classes but differed among years, ranging from 11% to 82% of total annual fawn mortality. Higher mortality of fawns born to 2-yr-old does appears to relate more to social behaviors such as loss of support by matriarchal does than to differences among age classes of does in habitat selection or in movement to areas where the hazard to fawns from hunting and highway accidents would be higher.

Long-term prospective study of postpartum thyroid dysfunction in women with insulin dependent diabetes mellitus.

Postpartum thyroid dysfunction (PPTD) is a common autoimmune disorder. Type I diabetes mellitus (IDDM) is an autoimmune disease with a high incidence of concomitant autoimmune thyroid failure. We hypothesized that women with IDDM would have an increased incidence of PPTD. Women with IDDM in New York City, were followed prospectively during the second and third trimester of pregnancy and at 6 weeks, 3 months, 6 months, 9 months, and 1 yr postpartum. A long-term follow-up was performed at 31 months postpartum. Forty-one women with IDDM were recruited at their initial prenatal visit. Two women (4.8%) had thyroid function test abnormalities observed at screening, three (7.3%) had a spontaneous miscarriage, and eight (19.5%) women were noncompliant with follow-up. Twenty-eight women (68.2%) completed the study. Thyroid function tests and thyroid autoantibody determinations were obtained at all visits. PPTD was defined as a TSH greater than 5.0 or less than 0.2 mU/L in the postpartum period with documented normal thyroid function tests during pregnancy. The incidence of PPTD in women with IDDM was 25%. This is a 3-fold increase compared to a similar study by our group in a nondiabetic population. Forty-three percent of the women (3/7) who developed PPTD required treatment in the immediate postpartum period and at long-term follow-up. The remainder of the women with PPTD, as well as all women who did not develop PPTD were euthyroid at 31 months postpartum. Women with IDDM are at high risk for PPTD. We recommend that all women with IDDM be screened for thyroid hormonal abnormalities during pregnancy and at 3 months postpartum for postpartum thyroid dysfunction. Long-term follow-up did not reveal an increased incidence of hypothyroidism in women who did not require treatment in the first postpartum year.

Prepregnancy weight and antepartum insulin secretion predict glucose tolerance five years after gestational diabetes mellitus.

To identify phenotypic, genotypic, and metabolic parameters measured at the time of antepartum diagnosis of gestational diabetes mellitus that can indicate the risk of diabetes mellitus at early postpartum (< or = 6 mo after delivery) and at a 5-yr follow-up. The recommendations from the National Diabetes Data Group and International Workshop Conferences on Gestational Diabetes Mellitus were used for screening, diagnosing, and subclassifying gestational diabetes mellitus. National Diabetes Data Group criteria were also used for classification of glucose tolerance postpartum. Plasma glucose, insulin, and free fatty acids were measured after an overnight fast. Plasma glucose and insulin were measured 15, 30, 60, 120, and 180 min after the 100-g oral glucose load. Postpartum glucose tolerance was evaluated at 3-6 mo (early), 1 yr, and annually thereafter. The 5-yr cumulative incidence of diabetes during follow-up after gestational diabetes mellitus was nearly 50%. Among those who had diabetes within 5 yr, a history of diabetes in only the mother was nearly threefold more common than a history of diabetes in only the father (30 vs. 11%, P < 0.01). Those who displayed diabetes at early postpartum (< or = 6 mo) testing had significantly higher antepartum glucose levels at 60, 120, and 180 min compared with those whose early postpartum results were normal. They were also relatively insulinopenic at antepartum testing. Their fasting, acutely stimulated (15 and 30 min), and integrated 3-h response to oral glucose were all significantly lower relative to women who remained normal or had impaired glucose tolerance at early postpartum testing. Women who developed diabetes between 6 mo and 5 yr postpartum were more obese before the index pregnancy, and they had lower fasting, acutely stimulated (15 and 30 min), and integrated (1-3 h) insulin levels compared with women who remained normal or displayed impaired glucose tolerance at 5 yr postpartum. A multiple logistic regression model showed that diabetes present at early postpartum testing was independently associated with higher 2-h glucose and lower basal and total integrated insulin level. Later (> or = 6 mo-5 yr postpartum) development of diabetes was independently associated with prepregnancy weight and impaired insulin secretion at diagnosis of gestational diabetes mellitus. Impaired beta-cell function and obesity at diagnosis of GDM were associated with the development of diabetes during a 5-yr, follow-up period. Studies designed to prevent diabetes in this high-risk group should examine strategies to maintain both optimal beta-cell function and maximum insulin sensitivity.

Leucine metabolism in lactating and dry goats: effect of insulin and substrate availability.

Early lactating goats show insulin resistance with respect to extramammary glucose utilization. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in lactating goats. To examine this question, the in vivo effect of acute insulin was studied in goats during early lactation (12-31 days postpartum), midlactation (98-143 days postpartum), and the dry period (approximately 1 yr postpartum). Insulin was infused (at 0.36 or 1.79 nmol/min) under euglycemic and eukaliemic clamps. In addition, appropriate amino acid infusion was used to blunt insulin-induced hypoaminoacidemia or to create hyperaminoacidemia and maintain this condition under insulin treatment. Leucine kinetics were assessed using a primed continuous infusion of L-[1-14C]-leucine, which started 2.5 h before insulin. In all animals the insulin treatments failed to stimulate the nonoxidative leucine disposal (an estimate of whole body protein synthesis) under both euaminoacidemic and hyperaminoacidemic conditions. Thus, in goat as well as humans, infusion of insulin fails to stimulate protein synthesis even when combined with a substantially increased provision of amino acids. In contrast, insulin treatments caused a dose-dependent inhibition of the endogenous leucine appearance (an estimate of whole body protein degradation). Under euaminoacidemia the initial slope from the plot of the endogenous leucine appearance as a function of plasma insulin (an insulin sensitivity index) was steeper during early lactation than when compared with the dry period. A similar trend occurred during midlactation but not to any significant degree. These differences were abolished under hyperaminoacidemia. It was concluded that the ability of physiological insulin to inhibit protein degradation was improved during lactation, demonstrating a clear-cut dissociation between the effects of insulin on protein and glucose metabolism. This adaptation no doubt may provide a mechanism to save body protein.

Antithyroid microsomal autoantibodies and HLA-DR5 are associated with postpartum thyroid dysfunction: evidence supporting an autoimmune pathogenesis.

Antithyroid microsomal antibodies (AMA) and human leukocyte antigen (HLA) haplotypes were assessed as markers for the occurrence of postpartum thyroid dysfunction (all forms) and postpartum painless thyroiditis with transient hyperthyroidism, respectively. AMA titers and thyroid function tests were measured sequentially in 261 mothers from delivery to up to 1 yr postpartum. To test for the association of HLA haplotypes in the subgroup of women with postpartum painless thyroiditis with hyperthyroidism, typing for HLA-A, -B, -C, -DR, and -DQ antigens was carried out in a selected group of 38 mothers with this syndrome. Their results were compared to those in 60 women with hypothyroid goitrous autoimmune thyroiditis and 98 regional controls. In the AMA study, 40 (15%) of the 261 mothers had positive AMA titers (titer, less than or equal to 1:80) at delivery, 54 (21%) 2-4 months postpartum, 69 (26%) 5-7 months postpartum, and 60 (23%) 1 yr postpartum. Among 55 mothers who developed postpartum thyroid dysfunction, 25 (47%) had positive AMA at delivery [relative risk (RR), 10.0; P less than 0.001; sensitivity, 45%; specificity, 95%]. Two to 4 months postpartum, 46 mothers had thyroid dysfunction, of whom 35 (76%) had positive AMA, while only 19 of the 215 euthyroid mothers (9%) had positive tests for AMA. Positive AMA tests at these times resulted in a RR for postpartum thyroid dysfunction of 32.8 (P less than 0.0001; sensitivity, 76%; specificity, 91%). Five to 7 months postpartum, 55 mothers had thyroid dysfunction, of whom 47 (86%) had positive AMA, while only 22 of 206 euthyroid mothers (11%) were positive (RR, 59.0; P less than 0.0001; sensitivity, 86%; specificity, 90%). In the HLA studies, DR5 occurred in 11 of 38 (29%) women with postpartum painless thyroiditis with hyperthyroidism vs. 12 of 98 (12%) controls, resulting in a RR of 2.9 (P less than 0.05). HLA-DR5 was present in 22 of 60 (37%) patients with goitrous autoimmune thyroiditis (RR, 4.2; P less than 0.01). HLA-DR4 and HLA-DQw3 were slightly but not significantly increased in women with postpartum painless thyroiditis with hyperthyroidism and goitrous autoimmune thyroiditis compared to those in normal controls. DQw1 was reciprocally decreased (P less than 0.025) in the women with goitrous autoimmune thyroiditis, but not in the women with postpartum painless thyroiditis with hyperthyroidism compared to that in normal controls...

Long term follow-up and HLA association in patients with postpartum hypothyroidism.

The long term clinical outcome of postpartum hypothyroidism was investigated by follow-up studies of 44 patients (59 postpartum episodes; mean age of mothers at delivery, 28.2 yr) 5 or more yr later (mean interval after delivery, 8.7 yr; range, 5-16 yr). Forty-nine episodes (83%) in 34 women were followed by recovery within 1 yr postpartum, and those women remained euthyroid thereafter (group A); 10 women [10 episodes (17%)] developed permanent hypothyroidism during the follow-up period (group B). Five women in group B recovered during the first year, but became hypothyroid again later, the other 5 women in Group B remained persistently hypothyroid. HLA typing revealed significantly higher frequencies of HLA-DR3, -DRW8, -DRW9, -A26, -BW46, and -BW67, and significantly lower frequencies of HLA-DR2, -BW52, -BW62, and -CW7 in women with postpartum hypothyroidism than in normal women. Of 9 women with postpartum hypothyroidism who had HLA-DRW9 and/or -B51 associated with antithyroglobulin-antibody titers of 2(3) X 10 or higher, 6 developed permanent hypothyroidism. We conclude that long term follow-up is essential for women of postpartum hypothyroidism because of the risk of permanent hypothyroidism. The results suggest that some immunogenetic factors may be related to the etiology of postpartum hypothyroidism and that women with HLA-DRW9 and/or -B51 and higher titers of antithyroglobulin antibody are likely to develop permanent hypothyroidism.