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Background: Severe iodine deficiency or excess during pregnancy can cause congenital hypothyroidism (CH). Iodine deficiency is common in pregnant women in the United States.Objectives: We conducted a nested case-control study in a cohort of ∼2.5 million births in California to determine whether iodine status is related to CH in a US population.Methods: Dried blood spots from 907 newborns with CH identified by newborn screening and 909 unaffected controls matched by month of birth were obtained from the California Newborn Screening Program to measure whole-blood iodine concentration. Iodine status was compared between cases and controls, and logistic regression was used to assess the association between CH status and blood iodine concentrations. Iodine status was also compared between cases and controls among infants treated in a neonatal intensive care unit (NICU) because CH has been reported in infants exposed to high levels of iodine in the NICU.Results: Blood iodine concentrations did not differ significantly between cases (median: 20.0 ng/mL; IQR: 12.1-29.8 ng/mL) and controls (median: 20.3 ng/mL; IQR: 12.5-30.9 ng/mL; P = 0.59). Neither extremely high nor extremely low blood iodine concentrations (1st, 5th, 95th, and 99th percentiles of the distribution) were more common in cases. Among infants treated in NICUs, however, cases had significantly (P = 0.01) higher iodine (median: 22.7 ng/mL; IQR: 16.4-32.1 ng/mL) compared with controls (median: 17.3 ng/mL; IQR: 8.3-26.6 ng/mL).Conclusions: CH cases did not have significantly higher or lower iodine in this population, which is reassuring given that maternal iodine deficiency is common in the United States. Among newborns in the NICU, CH cases had higher blood iodine concentrations compared with controls, suggesting that excess iodine exposure in the NICU could be causing CH. It may be beneficial to monitor iodine exposure from surgical procedures, imaging, and iodine-containing disinfectants and to consider non-iodine alternatives. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to determine whether newborn concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) are associated with early childhood growth.Methods: A total of 1,954 singletons and 966 twins from the Upstate KIDS Study (born 2008-2010) were included in this study. Newborn dried blood spot concentrations of PFOS, PFOA, and BPA were quantified by liquid chromatography tandem mass spectrometry. Children's weight and height were reported from birth through 3 years of age. Repeated measures were modeled using generalized linear mixed models.Results: PFOS and PFOA were associated with lower BMI (-0.078 kg/m2 [-0.12 to -0.038] and -0.076 kg/m2 [-0.17 to -0.051] per 1 standard deviation increase in log PFOS and PFOA, respectively) and not with early obesity among singletons. Inconsistent associations were observed for twins. BPA levels were higher among neonates with a neonatal intensive care unit stay (P < 0.001), making associations difficult to interpret.Conclusions: Perfluorinated alkyl substances did not exhibit obesogenic associations with early measures of childhood growth. Blood-based BPA measures are limited by the nonpersistent nature of the chemical, and unknown sources from hospital settings may present only transient exposures. [ABSTRACT FROM AUTHOR]

Background Little is known about the predictors of sexual intercourse frequency (SIF) among couples trying to conceive despite the well-established link between SIF and fecundity. Aim To evaluate men's and women's demographic, occupational, and lifestyle predictors of SIF among couples. Methods 469 Couples without a history of infertility participating in the Longitudinal Investigation of Fertility and the Environment Study (2005–2009) were followed up for ≤1 year while trying to conceive. At enrollment, both partners were interviewed about demographic, occupational, lifestyle, and psychological characteristics using standardized questionnaires. Multivariable generalized linear mixed models with Poisson distribution were used to estimate the adjusted percent difference in SIF across exposure categories. Outcomes SIF was recorded in daily journals and summarized as average SIF/mo. Results The median (interquartile range) SIF during follow-up was 6 (4–9) acts/mo. For every year increase in age for women and men, SIF decreased by –0.8% (95% CI –2.5 to 1.0%) and –1.7% (95% CI –3.1 to –0.3%). Women with high school education or less and those of non-white race had 34.4% and 16.0% higher SIF, respectively. A similar trend was seen for men's education and race. Only couples where both partners (but not just 1 partner) worked rotating shifts had –39.1% (95% CI –61.0 to –5.0%) lower SIF compared to couples where neither partner worked rotating shifts. Men's (but not women's) exercise was associated with 13.2% (95% CI 1.7–26.0%) higher SIF. Diagnosis of a mood or anxiety disorder in men (but not women) was associated with a 26.0% (95% CI –42.7 to –4.4%) lower SIF. Household income, smoking status, body mass index, night work, alcohol intake, and psychosocial stress were not associated with SIF. Clinical Translation Even among couples trying to conceive, there was substantial variation in SIF. Both partners' age, education, race, and rotating shift work as well as men's exercise and mental health play an important role in determining SIF. Conclusions As this was a secondary analysis of an existing study, we lacked information on many pertinent psychological and relationship quality variables and the hormonal status of participants, which could have affected SIF. The unique population-based couple design, however, captured both partners' demographics, occupational characteristics, and lifestyle behaviors in advance of their daily, prospective reporting of SIF, which was a major strength. Important predictors of SIF among couples attempting to conceive include men's exercise and mental health and both partners' age, education, race, and rotating shift work. Gaskins AJ, Sundaram R, Buck Louis GM, et al. Predictors of Sexual Intercourse Frequency Among Couples Trying to Conceive. J Sex Med 2018;15:519–528. [ABSTRACT FROM AUTHOR]

In biomedical studies, one is often interested in repeat events with longitudinal observations occurring only intermittently, resulting in panel count data. The first stage of labor, measured through unit-increments of cervical dilation in pregnant women, provides such an example. Obstetricians are interested in assessing the gap time distribution of per-unit increments of cervical dilation for better management of labor process. Typically, only intermittent medical examinations for cervical dilation occur after (already dilated) women get admitted to hospital. The observation frequency is very likely correlated to how fast/slow she dilates. Thus, one could view such data as panel count data with informative observation times and unknown start time. Here, we propose semiparametric proportional rate models for the event process and the observation process, with a multiplicative subject-specific frailty variable capturing the correlation between the two processes. Inference procedures for the gap times between consecutive events are proposed when the start times are known as well when unknown, using likelihood-based approach and estimating equations. The methodology is assessed through simulation study and through large sample property. A detailed analysis using the proposed methods is applied to data from two studies: the Collaborative Perinatal Project and the Consortium on Safe Labor. Supplementary materials for this article are available online. [ABSTRACT FROM AUTHOR]

Objective: To assess the morbidity associated with continuing the second-stage duration of labor, weighing the probability of spontaneous vaginal birth without morbidity compared with birth with serious maternal or neonatal complications.Methods: In a retrospective cohort, we analyzed singleton, vertex births at 36 weeks of gestation or greater without prior cesarean delivery (n=43,810 nulliparous and 59,605 multiparous women). We calculated rates of spontaneous vaginal birth and composite serious maternal or neonatal complications. Results were stratified by parity (nulliparous or multiparous) and epidural status (yes or no). Competing risks models were created for 1) spontaneous vaginal birth with no morbidity, 2) birth with maternal or neonatal morbidity, and 3) no spontaneous vaginal birth and no morbidity, and our main interest was in comparing number 1 against number 2.Results: Rates of spontaneous vaginal birth without morbidity were slightly higher after the first half hour (greater than 0.5-1.0 hours) for nulliparous women, after which rates decreased with increasing second-stage duration. For multiparous women, rates of spontaneous vaginal birth without morbidity decreased with increasing second-stage duration. For illustration, for a nulliparous woman with an epidural at 3.0 hours of the second stage of labor who extended by another 1.0 hour, her likelihood of delivering by spontaneous vaginal birth was 31.4% compared with her likelihood of birth with any serious complication in the subsequent hour, which was 7.6%. The percentage of cesarean deliveries for nonreassuring fetal heart rate tracing were higher for women without compared with women with an epidural.Conclusion: Rates of spontaneous vaginal birth without serious morbidity steadily decreased for increasing second-stage duration except for the first half hour for nulliparous women. We did not observe an inflection point at a particular hour mark for either spontaneous vaginal delivery without morbidity or births with morbidity. Our findings will assist in decision-making for extending second-stage duration. [ABSTRACT FROM AUTHOR]

Objective Equivocal findings have been reported on the association between maternal depression and children's growth, possibly because of the limited attention to its disproportionate impact by child sex. The relationship between the timing of maternal depression and children's growth was assessed in a population-based prospective birth cohort, with particular attention to sex differences. Methods The Upstate KIDS Study comprised 4,394 children followed through 3 years of age from 2008 to 2010. Maternal depression was measured antenatally by linkage with hospital discharge records before delivery and postnatally by depressive symptoms reported from questionnaires. Children's growth was measured by sex- and age-specific weight, height, weight for height, and BMI. Adjusted linear mixed effects models were used to estimate growth outcomes for the full sample and separately by plurality and sex. Results Antenatal depression was associated with lower weight for age (−0.24 z score units; 95% confidence interval [CI]: −0.43, −0.05) and height for age (−0.26 z score units; 95% CI: −0.51, −0.02) among singleton boys. Postnatal depressive symptoms were associated with higher weight for height (0.21 z score units; 95% CI: 0.01, 0.42) among singleton girls. Conclusions The findings of this study suggest that antenatal depression was associated with lower weight and smaller height only for boys, whereas postnatal depressive symptoms were associated with higher weight for height only for girls. The timing of depression and the mechanisms of sex-specific responses require further examination. [ABSTRACT FROM AUTHOR]

Background: Although pregnancy loss affects one-third of pregnancies, the associated signs/symptoms have not been fully described. Given the dynamic nature of maternal physiologic adaptation to early pregnancy, we posited the relationships between signs/symptoms and subsequent loss would vary weekly.Methods: In a preconception cohort with daily follow-up, pregnancies were ascertained by self-administered sensitive home pregnancy tests on day of expected menses. We evaluated the effects of weekly time-varying signs/symptoms (including vaginal bleeding, lower abdominal cramping, and nausea and/or vomiting) on pregnancy loss <20 weeks in Cox proportional hazards models and calculated the week-specific probability of loss by the presence/absence of each sign/symptom.Results: Of 341 pregnancies ascertained by home pregnancy test, 95 (28%) ended in loss. Relationships between signs/symptoms and loss varied across time since first positive pregnancy test. In the first week following pregnancy confirmation, when many losses occurred, bleeding [hazard ratio (HR) 8.7, 95% confidence interval (CI) 4.7, 16.0] and cramping (HR 1.8, 95% CI 1.2, 2.7) were associated with loss even when accompanied by nausea and/or vomiting (HR 5.2, 95% CI 2.6, 10.5). After the second week, new relationships emerged with nausea and/or vomiting inversely associated (HR range 0.6-0.3, all 95% CI upper bounds <1.00) and bleeding no longer associated with loss. Probabilities of loss of ranged from 78% (95% CI 59%, 96%) with bleeding present in week 1 to 8% (95% CI 5%, 12%) with nausea/vomiting present in week 5.Conclusions: Relationships between signs/symptoms and pregnancy loss vary in early pregnancy possibly reflecting maternal physiologic response. [ABSTRACT FROM AUTHOR]

Objective: To identify frequently reported prescription medications and supplements among couples planning pregnancy because there is a lack of descriptive information on these agents in women and men who are trying to conceive. Methods: Five hundred one couples enrolled in the Longitudinal Study of Infertility and the Environment, which took place between 2005 and 2009. Participants reported prescription medications as well as prescription and over-the-counter supplements used through interviews at study enrollment and through daily dairies during the 12-month follow-up. We identified prescription medications and supplements prospectively reported by ≥1% of women and men at baseline and from daily journal information grouped into 3-month preconception follow-up intervals while couples tried for pregnancy. Results: The 5 most reported prescription medications among women were levothyroxine (5.8%), cetirizine (2.6%), fluticasone (2.4%), escitalopram (1.8%), and fluoxetine (1.8%) and for men were lisinopril (2.0%), mometasone (2.0%), fexofenadine (1.8%), atorvastatin (1.6%), and montelukast (1.6%). The most reported supplements were multivitamins (63.3%, 43.5%) and fish oil (13.2%, 9.4%) for women and men, respectively, and prenatal vitamins (22.0%) for women. For women during the first 3 months of follow-up, prenatal vitamins (6.0%) and antibiotics (1.2%-2.6%) were among the most frequently started medications. During the next 3 months, clomiphene (4.5%) was the most frequently initiated medication. Conclusions: Couples trying for pregnancy reported a variety of prescription medications and supplements, and they differed by gender. Preconception guidance should address medication and supplement use to avoid potential exposures associated with adverse reproductive and perinatal outcomes. [ABSTRACT FROM AUTHOR]

Background: The relation between breastfeeding and early motor development is difficult to characterize because of the problems in existing studies such as incomplete control for confounding, retrospective assessment of infant feeding, and even the assessment of some motor skills too early. Objective: We sought to estimate associations between infant feeding and time to achieve major motor milestones in a US cohort. Design: The Upstate New York Infant Development Screening Program (Upstate KIDS Study) enrolled mothers who delivered live births in New York (2008-2010). Mothers of 4270 infants (boys: 51.7%) reported infant motor development at 4, 8, 12, 18, and 24 mo postpartum; information on infant feeding was reported at 4 mo. Accelerated failure time models were used to compare times to standing or walking across feeding categories while adjusting for parental characteristics, daycare, region, and infant plurality, sex, rapid weight gain, and baseline neurodevelopmental test results. Main models were stratified by preterm birth status. Results: The prevalence of exclusive breastfeeding in preterm infants was lower than in term infants at 4 mo postpartum (8% compared with 19%). After adjustment for confounders, term infants who were fed solids in addition to breast milk at 4 mo postpartum achieved both standing [acceleration factor (AF): 0.93; 95% CI: 0.87, 0.99] and walking (AF: 0.93; 95% CI: 0.88, 0.98) 7% faster than did infants who were exclusively breastfed, but these findings did not remain statistically significant after correction for multiple testing. We did not identify feeding-associated differences in motor milestone achievement in preterm infants. Conclusion: Our results suggest that differences in feeding likely do not translate into large changes in motor development. [ABSTRACT FROM AUTHOR]

Background: Imperfect follow-up in longitudinal studies commonly leads to missing outcome data that can potentially bias the inference when the missingness is nonignorable; that is, the propensity of missingness depends on missing values in the data. In the Upstate KIDS Study, we seek to determine if the missingness of child development outcomes is nonignorable, and how a simple model assuming ignorable missingness would compare with more complicated models for a nonignorable mechanism.Methods: To correct for nonignorable missingness, the shared random effects model (SREM) jointly models the outcome and the missing mechanism. However, the computational complexity and lack of software packages has limited its practical applications. This paper proposes a novel two-step approach to handle nonignorable missing outcomes in generalized linear mixed models. We first analyse the missing mechanism with a generalized linear mixed model and predict values of the random effects; then, the outcome model is fitted adjusting for the predicted random effects to account for heterogeneity in the missingness propensity.Results: Extensive simulation studies suggest that the proposed method is a reliable approximation to SREM, with a much faster computation. The nonignorability of missing data in the Upstate KIDS Study is estimated to be mild to moderate, and the analyses using the two-step approach or SREM are similar to the model assuming ignorable missingness.Conclusions: The two-step approach is a computationally straightforward method that can be conducted as sensitivity analyses in longitudinal studies to examine violations to the ignorable missingness assumption and the implications relative to health outcomes. [ABSTRACT FROM AUTHOR]