Hafsatou Diop

Perinatal outcomes associated with assisted reproductive technology: the Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART)

OBJECTIVE To compare on a population basis the birth outcomes of women treated with assisted reproductive technologies (ART), women with indicators of subfertility but without ART, and fertile women. DESIGN Longitudinal cohort study. SETTING Not applicable. PARTICIPANT(S) A total of 334,628 births and fetal deaths to Massachusetts mothers giving birth in a Massachusetts hospital from July 1, 2004, to December 31, 2008, subdivided into three subgroups for comparison: ART 11,271, subfertile 6,609, and fertile 316,748. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Four outcomes-preterm birth, low birth weight, small for gestational age, and perinatal death-were modeled separately for singletons and twins with the use of logistic regression for the primary comparison between ART births and those to the newly created population-based subgroup of births to women with indicators of subfertility but no ART. RESULT(S) For singletons, the risks for both preterm birth and low birth weight were higher for the ART group (adjusted odds ratios [AORs] 1.23 and 1.26, respectively) compared with the subfertile group, and risks in both the ART and the subfertile groups were higher than those among the fertile births group. For twins, the risk of perinatal death was significantly lower among ART births than fertile (AOR 0.55) or subfertile (AOR 0.15) births. CONCLUSION(S) The use of a population-based comparison group of subfertile births without ART demonstrated significantly higher rates of preterm birth and low birth weight in ART singleton births, but these differences are smaller than differences between ART and fertile births. Further refinement of the measurement of subfertile births and examination of the independent risks of subfertile births is warranted.

Early Diagnoses of Autism Spectrum Disorders in Massachusetts Birth Cohorts, 2001–2005

OBJECTIVE: We examined trends in autism spectrum disorder diagnoses by age 36 months (early diagnoses) and identified characteristics associated with early diagnoses. METHODS: Massachusetts birth certificate and early-intervention program data were linked to identify infants born between 2001 and 2005 who were enrolled in early intervention and receiving autism-related services before age 36 months (through December 31, 2008). Trends in early autism spectrum disorders were examined using Cochran-Armitage trend tests. χ2 Statistics were used to compare distributions of selected characteristics for children with and without autism spectrum disorders. Multivariate logistic regression analyses were conducted to identify independent predictors of early diagnoses. RESULTS: A total of 3013 children (77.5 per 10 000 study population births) were enrolled in early intervention for autism spectrum disorder by age 36 months. Autism spectrum disorder incidence increased from 56 per 10 000 infants among the 2001 birth cohort to 93 per 10 000 infants in 2005. Infants of mothers younger than 24 years of age, whose primary language was not English or who were foreign-born had lower odds of an early autism spectrum disorder diagnosis. Maternal age older than 30 years was associated with increased odds of an early autism spectrum disorder diagnosis. Odds of early autism spectrum disorders were 4.5 (95% confidence interval: 4.1–5.0) times higher for boys than girls. CONCLUSIONS: Early autism spectrum disorder diagnoses are increasing in Massachusetts, reflecting the national trend observed among older children. Linkage of early-intervention program data with population-based vital statistics is valuable for monitoring autism spectrum disorder trends and planning developmental and educational service needs.

Adverse pregnancy and birth outcomes associated with underlying diagnosis with and without assisted reproductive technology treatment

OBJECTIVE To compare the risks for adverse pregnancy and birth outcomes by diagnoses with and without assisted reproductive technology (ART) treatment to non-ART pregnancies in fertile women. DESIGN Historical cohort of Massachusetts vital records linked to ART clinic data from Society for Assisted Reproductive Technology Clinic Outcome Reporting System. SETTING Not applicable. PATIENT(S) Diagnoses included male factor (ART only), endometriosis, ovulation disorders, tubal (ART only), and reproductive inflammatory disorders (non-ART only). Pregnancies resulting in singleton and twin live births from 2004 to 2008 were linked to hospital discharges in women who had ART treatment (n = 3,689), women with no ART treatment in the current pregnancy (n = 4,098), and non-ART pregnancies in fertile women (n = 297,987). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Risks of gestational diabetes, prenatal hospitalizations, prematurity, low birth weight, and small for gestational age were modeled using multivariate logistic regression with fertile deliveries as the reference group adjusted for maternal age, race/ethnicity, education, chronic hypertension, diabetes mellitus, and plurality (adjusted odds ratios [AORs] and 95% confidence intervals [CIs]). RESULT(S) Risk of prenatal hospital admissions was increased for endometriosis (ART: 1.97, 1.38-2.80; non-ART: 3.34, 2.59-4.31), ovulation disorders (ART: 2.31, 1.81-2.96; non-ART: 2.56, 2.05-3.21), tubal factor (ART: 1.51, 1.14-2.01), and reproductive inflammation (non-ART: 2.79, 2.47-3.15). Gestational diabetes was increased for women with ovulation disorders (ART: 2.17, 1.72-2.73; non-ART: 1.94, 1.52-2.48). Preterm delivery (AORs, 1.24-1.93) and low birth weight (AORs, 1.27-1.60) were increased in all groups except in endometriosis with ART. CONCLUSION(S) The findings indicate substantial excess perinatal morbidities associated with underlying infertility-related diagnoses in both ART-treated and non-ART-treated women.

Pregnancy outcomes among women with intellectual and developmental disabilities

BACKGROUND There is currently no population-based research on the maternal characteristics or birth outcomes of U.S. women with intellectual and developmental disabilities (IDDs). Findings from small-sample studies among non-U.S. women indicate that women with IDDs and their infants are at higher risk of adverse health outcomes. PURPOSE To describe the maternal characteristics and outcomes among deliveries to women with IDDs and compare them to women with diabetes and the general obstetric population. METHODS Data from the 1998-2010 Massachusetts Pregnancy to Early Life Longitudinal database were analyzed between November 2013 and May 2014 to identify in-state deliveries to Massachusetts women with IDDs. RESULTS Of the 916,032 deliveries in Massachusetts between 1998 and 2009, 703 (<0.1%) were to women with IDDs. Deliveries to women with IDDs were to those who were younger, less educated, more likely to be black and Hispanic, and less likely to be married. They were less likely to identify the father on the infants birth certificate, more likely to smoke during pregnancy, and less likely to receive prenatal care during the first trimester compared to deliveries to women in the control groups (p<0.01). Deliveries to women with IDDs were associated with an increased risk of adverse outcomes, including preterm delivery, very low and low birth weight babies, and low Apgar scores. CONCLUSIONS Women with IDDs are at a heightened risk for adverse pregnancy outcomes. These findings highlight the need for a systematic investigation of the pregnancy-related risks, complications, costs, and outcomes of women with IDDs.

Identifying women with indicators of subfertility in a statewide population database: operationalizing the missing link in assisted reproductive technology research

OBJECTIVE To identify a group of deliveries to mothers with indicators of subfertility (SUBFERTILITY). DESIGN Longitudinal cohort study. SETTING Hospital. PATIENT(S) A total of 334,152 deliveries to Massachusetts mothers in a Massachusetts hospital between July 1, 2004, and December 31, 2008. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Subfertility was defined by an indication on a current or past birth certificate or hospital utilization data of infertility or assisted reproductive technology (ART) cycle before index delivery and no indication of ART use with index delivery. RESULT(S) Initially, 12,367 deliveries met the inclusion criteria for SUBFERTILITY (8,019 from birth certificates, 2,777 from hospital data, 1,571 from prior ART treatment). Removing deliveries from more than one data source resulted in 10,764 unique deliveries. Removing deliveries resulting from ART treatments left 6,238 deliveries in the SUBFERTILITY category. Demographic analysis indicated that deliveries in SUBFERTILITY were more similar to those in the ART population than to those in the fertile population. CONCLUSION(S) We have demonstrated the feasibility of using existing population-based linked public health data sets to identify SUBFERTILITY deliveries, and we have used ART data to distinguish ART and SUBFERTILITY births. The SUBFERTILITY category can serve as a comparison group of subfertile patients for studies of ART delivery and longitudinal health outcomes.

Enrollment in Early Intervention Programs Among Infants Born Late Preterm, Early Term, and Term

OBJECTIVE: To compare the prevalence of and characteristics associated with early intervention (EI) program enrollment among infants born late preterm (34–36 weeks’ gestation), early term (37–38 weeks’ gestation), and term (39–41 weeks’ gestation). METHODS: A Massachusetts cohort of 554 974 singleton infants born during 1998 through 2005 and survived the neonatal period was followed until the third birthday of each infant. Data came from the Pregnancy to Early Life Longitudinal Data System that linked birth certificates, birth hospital discharge reports, death certificates, and EI program enrollment records. We calculated prevalence and adjusted risk ratios to compare differences and understand associations. RESULTS: The prevalence of EI program enrollment increased with each decreasing week of gestation before 41 weeks (late preterm [23.5%], early term [14.9%], and term [11.9%]. In adjusted analyses, the strongest predictors of EI enrollment (adjusted risk ratio ≥1.20) for all gestational age groups were male gender, having a congenital anomaly, and having mothers who were ≥40 years old, nonhigh school graduates, and recipients of public insurance. CONCLUSIONS: Infants born late preterm and early term have higher prevalence of EI program services enrollment than infants born at term, and may benefit from more frequent monitoring for developmental delays or disabilities.

Severe Maternal Morbidity and the Use of Assisted Reproductive Technology in Massachusetts.

OBJECTIVE: To assess whether risk of severe maternal morbidity at delivery differed for women who conceived using assisted reproductive technology (ART), those with indicators of subfertility but no ART (“subfertile”), and those who had neither ART nor subfertility (“fertile”). METHODS: This retrospective cohort study was part of the larger Massachusetts Outcomes Study of Assisted Reproductive Technology. To construct the Massachusetts Outcomes Study of Assisted Reproductive Technology database and identify ART deliveries, we linked ART treatment records to birth certificates and maternal and infant hospitalization records occurring in Massachusetts between 2004 and 2010. An algorithm of International Classification of Diseases, 9th Revision, Clinical Modification diagnosis and procedure codes identified severe maternal morbidity. We used logistic generalized estimating equations to estimate odds of severe maternal morbidity associated with fertility status, adjusting for maternal demographic and health factors and gestational age, stratifying on plurality and method of delivery. RESULTS: The prevalence of severe maternal morbidity among this population (n=458,918) was 1.16%. The overall, crude prevalences of severe maternal morbidity among fertile, subfertile, and ART deliveries were 1.09%, 1.44%, and 3.14%, respectively. The most common indicator of severe maternal morbidity was blood transfusion. In multivariable analyses, among singletons, ART was associated with increased odds of severe maternal morbidity compared with both fertile (vaginal: adjusted odds ratio [OR] 2.27, 95% confidence interval [CI] 1.78–2.88; cesarean: adjusted OR 1.67, 95% CI 1.40–1.98, respectively) and subfertile (vaginal: adjusted OR 1.97, 95% CI 1.30–3.00; cesarean: adjusted OR 1.75, 95% CI 1.30–2.35, respectively) deliveries. Among twins, only cesarean ART deliveries had significantly greater severe maternal morbidity compared with cesarean fertile deliveries (adjusted OR 1.48, 95% CI 1.14–1.93). CONCLUSION: Women who conceive through ART may have elevated risk of severe maternal morbidity at delivery, largely indicated by blood transfusion, even when compared with a subfertile population. Further research should elucidate mechanisms underlying this risk.

Smoking among Pregnant Women with Disabilities

PURPOSE The purpose of this study was to examine the prevalence of smoking before, during, and after pregnancy among a representative sample of Massachusetts women with and without disabilities. METHODS Data from the 2007 to 2009 Massachusetts Pregnancy Risk Assessment Monitoring System survey were used to estimate the prevalence of smoking by disability status. MAIN FINDINGS Disability prevalence was 4.8% (n = 204) among Massachusetts women giving birth during 2007 through 2009. The prevalence of smoking during the 3 months before pregnancy among women with disabilities was 37.3% (95% CI, 28.3-47.2%) compared with 18.3% (95% CI, 16.6-20.1%) among women without disabilities. Similarly, 25.2% (95% CI, 17.3-35.2%) of women with disabilities, compared with 9.4% of women without disabilities (95% CI, 8.1-10.8%), smoked during the last trimester of their pregnancy, and 32.1% of women with disabilities (95% CI, 23.5-42.1%) compared with 12.5% of women without disabilities (95% CI, 11.1-14.1%), smoked after pregnancy. In the multivariate logistic regression models, women with disabilities had significantly higher risks of smoking before, during and after pregnancy than women without disabilities (adjusted relative risk [aRR], 1.7 [95% CI, 1.2-2.2]; aRR, 1.9 [95% CI, 1.3-2.8]; aRR, 1.8 [95% CI, 1.3-2.5], respectively) while adjusting for race/Hispanic ethnicity, marital status, education, age, household poverty status, and infants birth year. IMPLICATIONS Women with disabilities are more likely to smoke before, during, and after their pregnancy and less likely to quit smoking during pregnancy. Efforts to integrate and target pregnant women with disabilities in smoking-cessation programs are vital.

Maternal characteristics and pregnancy outcomes after assisted reproductive technology by infertility diagnosis: ovulatory dysfunction versus tubal obstruction.

OBJECTIVE To examine differences in maternal characteristics and pregnancy outcomes between women with ovulatory dysfunction (OD) and women with tubal obstruction (TO) who underwent assisted reproductive technology (ART). DESIGN Retrospective cohort study. SETTING Centers for Disease Control and Prevention. PATIENT(S) Exposed and nonexposed groups were selected from the 2000-2006 National ART Surveillance System linked with live-birth certificates from three states: Florida, Massachusetts, and Michigan. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Maternal characteristics and pregnancy outcomes, including newborns health status right after delivery (Apgar score, <7 vs. ≥ 7) as the study outcome of interest, were assessed among women with OD/polycystic ovary syndrome (PCOS) and TO who used ART. RESULT(S) A significantly higher prevalence of women with OD/PCOS were younger (<35 years of age; 65.7% vs. 48.9%), were white (85.4% vs. 74.4%), had higher education (29.4% vs. 15.6%), and experienced diabetes (8.8% vs. 5.3%) compared with those having TO. The odds of having a lower (<7) Apgar score at 5 minutes were almost twice as high among newborns of women with OD/PCOS compared with those with TO (crude odds ratio, 1.86; 95% confidence interval [CI], 1.31, 2.64; adjusted odds ratio, 1.90; 95% CI, 1.30, 2.77). CONCLUSION(S) Women with OD/PCOS who underwent ART have different characteristics and health issues (higher prevalence of diabetes) and infant outcomes (lower Apgar score) compared with women with TO.

Is the wrong question being asked in infertility research

A persistent finding is that assisted reproductive technology (ART) is associated with compromised birth outcomes, including higher risks for prematurity, low birthweight, and congenital malformations, even among singletons. Over the past decade, our research group, the Massachusetts Outcome Study of Assisted Reproductive Technology (MOSART), has evaluated pregnancy and birth outcomes among three groups of women, those women treated with ART, those with indicators of subfertility but without ART treatment, and fertile women. We have also explored the influence of infertility-related diagnoses on outcomes for women and infants. Over the course of our research, we have changed our perspective from an original focus on ART treatment parameters as the primary cause of excess morbidity to one centered instead on the underlying infertility-related diagnoses. This paper summarizes the research findings from our group that support this change in focus for infertility-based research from a primary emphasis on ART treatment to greater attention to the contribution of preexisting pathology underlying the infertility and suggests directions for future analyses.