Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.

Neonatal outcomes according to different glucose threshold values in gestational diabetes: a register-based study.

BACKGROUND: Mild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using different oral glucose tolerance test (OGTT) thresholds. METHODS: This register-based study included all (n = 4,939) singleton pregnant women participating a 75 g 2-h OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting ≥ 5.3, 1 h ≥ 10.0 or 2-h glucose ≥ 8.6 mmol/L. Women who did not meet these criteria but met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1-5.2 mmol/L and/or 2-h glucose 8.5 mmol/L, n = 509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-h glucose 7.8-8.5 mmol/L, n = 166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups (n = 1292 and n = 612, respectively). Controls were normoglycaemic according to all criteria (fasting glucose < 5.1 mmol/L, 1-h glucose < 10.0 mmol/L and 2-h glucose < 8.5 mmol/L, n = 3031). Untreated mild hyperglycemia groups were compared to controls and treated GDM groups. The primary outcome - a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality - was analysed using multivariate logistic regression. RESULTS: The risk for the adverse neonatal outcome in untreated mild hyperglycemia was not increased compared to controls (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 0.71-1.44, using the IADPSG criteria; aOR: 1.05, 95% CI: 0.60-1.85, using the NICE criteria). The risk was lower compared to the treated IADPSG (aOR 0.38, 95% CI 0.27-0.53) or the treated NICE group (aOR 0.32, 95% CI 0.18-0.57). DISCUSSION: The risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia compared to normoglycaemic controls and was lower than in the treated GDM groups. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 h seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes.

Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk: A Nordic Population-Based Registry Study.

Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer ≥2 years after last birth (n = 7,425, 83% papillary). Cases were matched to controls (n = 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR = 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR = 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR = 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR = 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR = 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR = 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.

Indications for intensive care unit treatment among neonates born to mothers with thyroid disease: A population-based cohort study.

INTRODUCTION: Thyroid diseases in pregnancy are relatively common and are associated with adverse pregnancy and perinatal outcomes, increasing a neonate's risk of admission to the neonatal intensive care unit (NICU). The aim of this study was to evaluate the indications for increased risk of NICU admission among the neonates of hypothyroid and hyperthyroid mothers. MATERIAL AND METHODS: The study data consisted of all singleton deliveries (n = 734 773) between 2004 and 2016 in Finland collected from the Finnish Medical Birth Register. The odds of NICU admission (with 95% confidence intervals) were compared between the neonates of hypothyroid or hyperthyroid mothers and of mothers without any thyroid diseases by specified neonatal characteristics and morbidities using logistic regression analysis. The studied neonatal characteristics were preterm birth (<37+0 gestational weeks), low birthweight (<2500 g), the rate of small- and large-for-gestational age infants, and eight disease-specific neonatal outcomes: asphyxia, respiratory distress syndrome, meconium aspiration syndrome, pneumothorax, cardiovascular problems, infections, jaundice and hypoglycemia. RESULTS: The most common indications for NICU care were principally the same in the neonates of the mothers with and without thyroid disease: respiratory distress syndrome, infections, preterm birth, low birthweight and neonatal hypoglycemia. The preterm neonates, neonates with low birthweight, and large-for-gestational-age infants had increased odds of NICU admission if their mother had hypothyroidism. Also neonates with cardiovascular problems, jaundice or hypoglycemia associated with maternal diabetes had increased odds of NICU admissions if their mother had hypothyroidism. Further, the preterm neonates, large-for-gestational-age infants, and term infants with jaundice had increased odds of NICU admission if their mother had hyperthyroidism. CONCLUSIONS: The most common indications for NICU care were similar for the neonates of the mothers with and without thyroid disease. However, the neonates of the mothers with thyroid diseases were more likely to need NICU care. The neonates of the mothers with thyroid diseases had higher odds of NICU treatment in cases of preterm birth, large for gestational age, and hypoglycemia.

Iodine and thyroid status during pregnancy and risk of stillbirth: A population-based nested case-control study.

Prior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population-based nested case-control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid-stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio-economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2-Q3 OR = 0.92, 95% CI = 0.78-1.09; Q4 vs. Q2-Q3 OR = 0.78; 95% CI = 0.45-1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine-deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries.

Maternal hyperthyroidism and pregnancy outcomes: A population-based cohort study.

OBJECTIVE: Maternal hyperthyroidism and antithyroid medications have been associated with adverse pregnancy and perinatal outcomes. This nationwide register-based study investigated the association of maternal hyperthyroidism and antithyroid drug (ATD) use with pregnancy outcomes and included all singleton births in Finland between 2004 and 2013 (N = 571 785). DESIGN, PATIENTS AND MEASUREMENTS: Hyperthyroid mothers were identified in the Medical Birth Register, and data on ATD use before and/or during pregnancy were collected from the Prescription Register. The odds ratios, with 95% confidence intervals, for adverse outcomes among hyperthyroid mothers and mothers without thyroid disease were compared using logistic regression. RESULTS: In total, 2144 (0.37%) of all the women had diagnoses of hyperthyroidism, and 580 (27%) of these women had used ATDs before and/or during pregnancy. Compared to the mothers without thyroid disease, maternal hyperthyroidism was associated with older age, multiparity, smoking, previous miscarriages, and overweight or obesity. The mothers diagnosed with hyperthyroidism also had increased odds of gestational hypertensive disorders, caesarean sections, placental abruptions, preterm births, small-for-gestational-age newborns and neonatal intensive care unit treatment. The odds of pregnancy and/or perinatal complications were higher among those who had used ATDs (indicative of active disease), but those who had not received ATD treatment also had increased odds of such complications compared to the mothers without thyroid disease. CONCLUSIONS: Women with active hyperthyroidism and those with histories of hyperthyroidism should be considered at risk of developing pregnancy and perinatal complications and should therefore be monitored during pregnancy.

The joint role of thyroid function and iodine concentration on gestational diabetes risk in a population-based study.

INTRODUCTION: Iodine is essential for thyroid function, and iodine deficiency during pregnancy is common in Europe and the USA. However, no published studies have examined the role of iodine deficiency in the relation between thyroid function and gestational diabetes mellitus (GDM). MATERIAL AND METHODS: We conducted a population-based, nested case-control study within the Finnish Maternity Cohort using pregnancy and perinatal outcome data from the Finnish Maternal Birth Register. We randomly selected 224 GDM cases with singleton pregnancies and 224 controls without GDM from all singleton births occurring in Finland during 2012-2013. Blood was drawn at 10-14 weeks' gestation and analyzed for serum iodide, thyroglobulin, and thyroid-stimulating hormone (TSH) concentrations. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) of GDM. RESULTS: Very high thyroglobulin concentration (>95% percentile; >83 µg/L) was not associated with significantly altered odds of GDM compared to those with normal levels (OR 0.41; 95% CI: 0.12, 1.38). High concentrations of TSH were also not associated with increased odds of GDM compared to normal levels of TSH (OR 0.45; 95% CI: 0.06, 3.18). Women in the lowest 5th percentile (<1.58 ng/mL) of iodine did not have increased odds of GDM compared to those with iodide in the highest quartile (OR 0.39; 95% CI: 0.11, 1.35). CONCLUSIONS: Low levels of iodide and thyroid function in early pregnancy are not associated with increased risk of GDM in this mildly iodine-deficient population.

Ambient temperature and risk of cardiovascular events at labor and delivery: A case-crossover study.

BACKGROUND: Extreme ambient temperatures are linked to cardiac events in the general population, but this relationship is unclear among pregnant women. We estimated the associations and attributable risk between ambient temperature and the risk of cardiovascular event at labor/delivery, and investigated whether these associations vary by maternal race/ethnicity. METHODS: We identified 680 women with singleton deliveries affected by cardiovascular events across 12 US sites (2002-2008). Average daily temperature during the week before, delivery day, and each of the seven days before delivery was estimated for each woman. In a case-crossover analysis, exposures during these hazard periods were compared to two control periods before and after delivery using conditional logistic regression adjusted for other environmental factors. RESULTS: During the cold season (October-April), 1°C lower during the week prior to delivery was associated with a 4% (95% CI: 1-7%) increased risk of having a labor/delivery affected by cardiovascular events including cardiac arrest and stroke. During the warm season (May-September), 1°C higher during the week prior was associated with a 7% (95% CI: 3-12%) increased risk. These risks translated to 13.4 and 23.9 excess events per 100,000 singleton deliveries during the cold and warm season, respectively. During the warm season, the risks were more pronounced on days closer to delivery and Black women appeared to be more susceptible to the same temperature increase. CONCLUSION: Small changes in temperature appear to affect the risk of having cardiovascular events at labor/delivery. Black women had a differentially higher warm season risk. These findings merit further investigation.

Preterm birth and air pollution: Critical windows of exposure for women with asthma.

BACKGROUND: Ambient air pollutants may increase preterm birth (PTB) risk, but critical exposure windows are uncertain. The interaction of asthma and pollutant exposure is rarely studied. OBJECTIVE: We sought to assess the interaction of maternal asthma and air pollutant exposures in relation to PTB risk. METHODS: Electronic medical records for 223,502 US deliveries were linked with modified Community Multiscale Air Quality model outputs. Logistic regression with generalized estimating equations estimated the odds ratio and 95% CIs for PTB on the basis of the interaction of maternal asthma and particulate matter with aerodynamic diameter of less than 2.5 microns and particulate matter with aerodynamic diameter of less than 10 microns, ozone (O3), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO) per interquartile range. For each gestational week 23 to 36, exposures among women who delivered were compared with those remaining pregnant. Three-month preconception, whole pregnancy, weeks 1 to 28, and the last 6 weeks of gestation averages were also evaluated. RESULTS: On assessing PTB by gestational week, we found that significant asthma interactions were sporadic before 30 weeks but more common during weeks 34 to 36, with higher risk among mothers with asthma for NOx, CO, and SO2 exposure and an inverse association with O3 in week 34. Odds of PTB were significantly higher among women with asthma for CO and NOx exposure preconception and early in pregnancy. In the last 6 weeks of pregnancy, PTB risk associated with particulate matter with aerodynamic diameter of less than 10 microns was higher among women with asthma. CONCLUSIONS: Mothers with asthma may experience a higher risk for PTB after exposure to traffic-related pollutants such as CO and NOx, particularly for exposures 3-months preconception and in the early weeks of pregnancy.

Controlled direct effects of preeclampsia on neonatal health after accounting for mediation by preterm birth.

BACKGROUND: Preeclampsia is characterized by alterations in angiogenic factors that may increase neonatal morbidity independent of preterm birth. METHODS: We estimated the controlled direct effect of preeclampsia on neonatal outcomes independent of preterm birth among 200,103 normotensive and 10,507 preeclamptic singleton pregnancies in the Consortium on Safe Labor (2002-2008). Marginal structural models with stabilized inverse probability weights accounted for potential confounders in the pathway from preeclampsia to preterm birth to neonatal outcomes, including mediator-outcome confounders related to preeclampsia status, such as cesarean delivery. Controlled direct effects of preeclampsia on perinatal mortality, small for gestational age (SGA), neonatal intensive care unit (NICU) admission, respiratory distress syndrome, transient tachypnea of the newborn, anemia, apnea, asphyxia, peri- or intraventricular hemorrhage, and cardiomyopathy were estimated for the hypothesized intervention of term delivery for all infants. RESULTS: When delivery was set at ≥37 weeks, preeclampsia increased the odds of perinatal mortality (odds ratio = 2.2 [95% confidence interval = 1.1-4.5], SGA = (1.9 [1.8-2.1]), NICU admission (1.9 [1.7-2.1]), respiratory distress syndrome (2.8 [2.0-3.7], transient tachypnea of the newborn (1.6 [1.3-1.9]), apnea (2.2 [1.6-3.1]), asphyxia (2.7 [1.5-4.9]), and peri- or intraventricular hemorrhage (3.2 [1.4-7.7]). No direct effect of preeclampsia at term was observed for anemia or cardiomyopathy. Our results appear robust in the presence of moderate confounding, and restriction to severe preeclampsia yielded similar findings. CONCLUSION: Preeclampsia was directly associated with adverse neonatal outcomes beyond morbidity mediated by preterm birth. Although severe neonatal outcomes were less common at later gestational ages, marginal structural models suggested elevated neonatal risk due to preeclampsia even if it was possible to deliver all infants at term.

Preconception and early pregnancy air pollution exposures and risk of gestational diabetes mellitus.

BACKGROUND: Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk. METHODS: Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) ≤ 2.5µm (PM2.5) and PM2.5 constituents, PM ≤ 10µm (PM10), nitrogen oxides (NOx), carbon monoxide, sulfur dioxide (SO2) and ozone (O3) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1-24 based on modified Community Multiscale Air Quality models for delivery hospital referral regions. Binary regression models with robust standard errors estimated relative risks (RR) for GDM per interquartile range (IQR) increase in pollutant concentrations adjusted for study site, maternal age and race/ethnicity. RESULTS: Preconception maternal exposure to NOX (RR=1.09, 95% CI: 1.04, 1.13) and SO2 (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and risk estimates remained elevated for first trimester exposure. Preconception O3 was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks increased later in pregnancy. CONCLUSION: Maternal exposures to NOx and SO2 preconception and during the first few weeks of pregnancy were associated with increased GDM risk. O3 appeared to increase GDM risk in association with mid-pregnancy exposure but not in earlier time windows. These common exposures merit further investigation.

Neonatal health of infants born to mothers with asthma.

BACKGROUND: Maternal asthma is associated with serious pregnancy complications, but newborn morbidity is understudied. OBJECTIVE: We wanted to determine whether infants of asthmatic mothers have more neonatal complications. METHODS: The Consortium on Safe Labor (2002-2008), a retrospective cohort, included 223,512 singleton deliveries at ≥ 23 weeks' gestation. Newborns of mothers with asthma (n = 17,044) were compared with newborns of women without asthma by using logistic regression models with generalized estimating equations to calculate adjusted odds ratios (ORs) and 95% CIs. Electronic medical record data included gestational week at delivery, birth weight, resuscitation, neonatal intensive care unit (NICU) admission, NICU length of stay, hyperbilirubinemia, respiratory distress syndrome, apnea, sepsis, anemia, transient tachypnea of the newborn, infective pneumonia, asphyxia, intracerebral hemorrhage, seizure, cardiomyopathy, periventricular or intraventricular hemorrhage, necrotizing enterocolitis, aspiration, retinopathy of prematurity, and perinatal mortality. RESULTS: Preterm delivery was associated with maternal asthma for each week after 33 completed weeks of gestation and not earlier. Maternal asthma also increased the adjusted odds of small for gestational age (OR = 1.10; 95% CI, 1.05-1.16), NICU admission (OR = 1.12; 95% CI, 1.07-1.17), hyperbilirubinemia (OR = 1.09; 95% CI, 1.04-1.14), respiratory distress syndrome (OR = 1.09; 95% CI, 1.01-1.19), transient tachypnea of the newborn (OR = 1.10; 95% CI, 1.02-1.19), and asphyxia (OR = 1.34; 95% CI, 1.03-1.75). Findings persisted for term infants (≥ 37 weeks) who had additional increased odds of intracerebral hemorrhage (OR = 1.84; 95% CI, 1.11-3.03) and anemia (OR = 1.30; 95% CI, 1.04-1.62). CONCLUSIONS: Maternal asthma was associated with prematurity and small for gestational age. Adverse neonatal outcomes, including respiratory complications, hyperbilirubinemia, and NICU admission, were increased in association with maternal asthma even among term deliveries.

Elevated blood pressure in pregnancy and subsequent chronic disease risk.

BACKGROUND: Preeclampsia, a new-onset hypertensive disorder of pregnancy, is associated with lifetime cardiovascular disease risk, but less is known about risk after other pregnancy-related hypertension. METHODS AND RESULTS: The Northern Finland Birth Cohort 1966 included all expected births from 1 year (N=12 055 women). Blood pressure measurements and other prospective data were determined from prenatal care records and questionnaires for 10 314 women. Subsequent diagnoses were ascertained from Finnish registries (average follow-up, 39.4 years). Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) estimate risks in hypertensive women compared with normotensive women. Hypertension during pregnancy was associated with increased risk of subsequent cardiovascular disease and arterial hypertension. Women with chronic hypertension and superimposed preeclampsia/eclampsia had high risk for future diseases. Gestational hypertension was associated with increased risk of ischemic heart disease (HR, 1.44 [95% CI, 1.24-1.68]), myocardial infarcts (HR, 1.75 [95% CI, 1.40-2.19]), myocardial infarct death (HR, 3.00 [95% CI, 1.98-4.55]), heart failure (HR, 1.78 [95% CI, 1.43-2.21]), ischemic stroke (HR, 1.59 [95% CI, 1.24-2.04]), kidney disease (HR, 1.91 [95% CI, 1.18-3.09]), and diabetes mellitus (HR, 1.52 [95% CI, 1.21-1.89]). Isolated systolic hypertension was associated with increased risk of myocardial infarct death (HR, 2.15 [95% CI, 1.35-3.41]), heart failure (HR, 1.43 [95% CI, 1.13-1.82]), and diabetes mellitus (HR, 1.42 [95% CI, 1.13-1.78]), whereas isolated diastolic hypertension was associated with increased risk of ischemic heart disease (HR, 1.26 [95% CI, 1.05-1.50]). Results were similar in nonsmoking women aged <35 years with normal weight and no diabetes mellitus during pregnancy. CONCLUSIONS: Elevated blood pressure during pregnancy, regardless of type and even without known risk factors, signals high risk of later cardiovascular disease, chronic kidney disease, and diabetes mellitus. Clinical monitoring, risk factor evaluation, and early intervention could benefit women with hypertension in pregnancy.

Neonatal outcomes in early term birth.

OBJECTIVE: To determine neonatal morbidity rates for early term birth compared with full term birth by precursor leading to delivery. STUDY DESIGN: This was a retrospective study of 188,809 deliveries from 37 0/7 to 41 6/7 weeks of gestation with electronic medical record data from 2002 to 2008. Precursors for delivery were categorized as spontaneous labor, premature rupture of membranes indicated, and no recorded indication. After excluding anomalies, rates of neonatal morbidities by precursor were compared at each week of delivery. RESULTS: Early term births (37 0/7-38 6/7 weeks) accounted for 34.1% of term births. Overall, 53.6% of early term births were due to spontaneous labor, followed by 27.6% indicated, 15.5% with no recorded indication, and 3.3% with premature rupture of membranes. Neonatal intensive care unit admission and respiratory morbidity were lowest at or beyond 39 weeks compared with the early term period for most precursors, although indicated deliveries had the highest morbidity compared with other precursors. The greatest difference in morbidity was between 37 and 39 weeks for most precursors, although most differences in morbidities between 38 and 39 weeks were not significant. Respiratory morbidity was higher at 37 than 39 weeks regardless of route of delivery. CONCLUSION: Given the higher neonatal morbidity at 37 compared with 39 weeks regardless of delivery precursor, our data support recent recommendations for designating early term to include 37 weeks. Prospective data is urgently needed to determine the optimal timing of delivery for common pregnancy complications.

Racial/ethnic differences in pregnancy-related hypertensive disease in nulliparous women.

OBJECTIVE: Hypertension and cardiovascular disease rates vary by race/ethnicity in nonpregnant adults. We aimed to examine racial/ethnic differences in prevalence and severity of hypertensive diseases during pregnancy in nulliparous women. DESIGN, SETTING, PARTICIPANTS: Nulliparous women with singleton deliveries and electronic medical record data on demographics and pregnancy outcomes (n = 56,617) were selected from the Consortium on Safe Labor (2002-2008). Multivariable logistic regression was performed to calculate the adjusted odds of gestational hypertension, mild preeclampsia, severe preeclampsia, eclampsia, chronic hypertension, superimposed preeclampsia, and unspecified hypertension for women who were non-Hispanic Black, Hispanic, Asian/Pacific Islander, and multiracial/other race/ethnicity, compared with non-Hispanic White women. RESULTS: Non-Hispanic Black women had higher odds of entering pregnancy with chronic hypertension (adjusted odds ratio (AOR) = 1.43, 95% confidence interval (CI) 1.11-1.84) and had higher odds of developing mild (AOR = 1.26, 95% Cl 1.10-1.45), severe (AOR = 1.31, 95% Cl 1.10-1.57) or superimposed preeclampsia (AOR = 1.98, 95% ClI 1.40-2.80) compared to non-Hispanic White women. Hispanic women and Asian/Pacific Islanders had higher odds of remaining normotensive (AOR = 1.22, 95% CI 1.12-1.33 and AOR=1.55, 95% CI 1.31-1.84, respectively). Conclusions: Odds for specific gestational hypertensive diseases varied by race/ethnicity among women during their first pregnancy. Non-Hispanic Black women experienced more severe disease, while Hispanic women and Asian/Pacific Islanders had an overall decreased risk compared to non-Hispanic Whites. Patterns of racial/ethnic variation associated with hypertensive diseases during pregnancy were similar to racial/ethnic associations reported for adult-onset cardiovascular disease, suggesting that there may be common pathways and shared risk factors.

Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis.

CONTEXT: Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes. OBJECTIVE: To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes. METHODS: We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders. RESULTS: The final study population comprised 33 118 mother-child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA. CONCLUSION: This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

CONTEXT: Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. METHODS: We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. RESULTS: The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. CONCLUSION: Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

Neonatal outcomes and birth weight in pregnancies complicated by maternal thyroid disease.

Maternal hypothyroidism has previously been shown to increase risk for neonatal intensive care treatment, but otherwise the association between thyroid diseases and neonatal morbidity is understudied. The Consortium on Safe Labor, a retrospective cohort (2002-2008), included 223,512 singleton deliveries of which 0.2% had hyperthyroidism, 1.4% primary and 0.1% iatrogenic hypothyroidism, and 1.3% other/unspecified thyroid disease. Logistic regression with generalized estimating equations estimated adjusted odds ratios of adverse outcomes. Intensive care treatment was more common for neonates of women with thyroid disease. Hyperthyroidism and primary hypothyroidism were associated with sepsis, respiratory distress syndrome, transient tachypnea, and apnea. Iatrogenic hypothyroidism was associated with sepsis and neonatal anemia. Hyperthyroidism was also associated with rare outcomes (prevalence, <1%) including cardiomyopathy, retinopathy of prematurity, and neonatal thyroid diseases. Hyperthyroid non-Hispanic black women had higher odds of term infants that weighed <2,500 g, and hypothyroid non-Hispanic white women had higher odds of large-for-gestational-age infants. These analyses were stratified by race/ethnicity due to interaction. Associations were similar in analyses restricted to term infants. In conclusion, thyroid diseases were associated with increased neonatal morbidity. Although we lacked data on treatment during pregnancy, these nationwide data suggest a need for better thyroid disease management to reduce neonatal morbidity.

Obstetric complications among US women with asthma.

OBJECTIVE: We sought to characterize complications of pregnancy, labor, and delivery associated with maternal asthma in a contemporary US cohort. STUDY DESIGN: We studied a retrospective cohort based on electronic medical record data from 223,512 singleton deliveries from 12 clinical centers across the United States from 2002 through 2008. RESULTS: Women with asthma had higher odds of preeclampsia (adjusted odds ratio [aOR], 1.14; 95% confidence interval [CI], 1.06-1.22), superimposed preeclampsia (aOR, 1.34; 95% CI, 1.15-1.56), gestational diabetes (aOR, 1.11; 95% CI, 1.03-1.19), placental abruption (aOR, 1.22; 95% CI, 1.09-1.36), and placenta previa (aOR, 1.30; 95% CI, 1.08-1.56). Asthmatic women had a higher odds of preterm birth overall (aOR, 1.17; 95% CI, 1.12-1.23) and of medically indicated preterm delivery (aOR, 1.14; 95% CI, 1.01-1.29). Asthmatics were less likely to have spontaneous labor (aOR, 0.87; 95% CI, 0.84-0.90) and vaginal delivery (aOR, 0.84; 95% CI, 0.80-0.87). Risks were higher for breech presentation (aOR, 1.13; 95% CI, 1.05-1.22), hemorrhage (aOR, 1.09; 95% CI, 1.03-1.16), pulmonary embolism (aOR, 1.71; 95% CI, 1.05-2.79), and maternal intensive care unit admission (aOR, 1.34; 95% CI, 1.04-1.72). CONCLUSION: Maternal asthma increased risk for nearly all outcomes studied in a general obstetric population.