Wanda D. Barfield

Assisted Reproductive Technology Surveillance - United States, 2014.

Problem/Condition Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks to both mothers and infants, including obstetric complications, preterm delivery, and low birthweight infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2014 and compares birth outcomes that occurred in 2014 (resulting from ART procedures performed in 2013 and 2014) with outcomes for all infants born in the United States in 2014. Period Covered 2014. Description of System In 1996, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102–493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). Results In 2014, a total of 169,568 ART procedures (range: 124 in Wyoming to 21,018 in California) with the intent to transfer at least one embryo were performed in 458 U.S. fertility clinics and reported to CDC. These procedures resulted in 56,028 live-birth deliveries (range: 52 in Wyoming to 7,230 in California) and 68,782 infants born (range: 64 in Wyoming to 8,793 in California). Nationally, the total number of ART procedures performed per million women of reproductive age (15–44 years), a proxy measure of the ART usage rate, was 2,647 (range: 364 in Puerto Rico to 6,726 in Massachusetts). ART use exceeded the national average in 13 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Virginia). Eight reporting areas (Connecticut, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, and New York) had rates of ART use exceeding 1.5 times the national average. Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.7 among women aged <35 years, 1.9 among women aged 35–37 years, and 2.3 among women aged >37 years). Among women aged <35 years, who typically are considered to be good candidates for elective single embryo transfer (eSET) procedures, the national eSET rate was 28.5% (range: 4.3% in Puerto Rico to 67.9% in Delaware). In 2014, ART contributed to 1.6% of all infants born in the United States (range: 0.4% in Puerto Rico to 4.7% in Massachusetts) and 18.3% of all multiple-birth infants (range: 5.5% in Alaska and West Virginia to 37.3% in Hawaii), including 18.0% of all twin infants (range: 5.2% in some states to 36.2% in Hawaii) and 26.4% of all triplets and higher-order infants (range: 0% in some states to 65.2% in Hawaii). Percentages of live births that were multiple-birth deliveries were higher among infants conceived with ART (39.4%; range: 11.5% in Delaware to 55.6% in Puerto Rico) than among all infants born in the total birth population (3.5%; range: 2.2% in Puerto Rico to 4.4% in New Jersey). Approximately 38.0% of ART-conceived infants were twin infants, and 2.0% were triplets and higher-order infants. ART-conceived twins accounted for approximately 95.3% of all ART-conceived infants born in multiple deliveries. Nationally, infants conceived with ART contributed to 5.5% of all low birthweight (<2,500 g) infants (range: 1.2% in West Virginia to 14.2% in Massachusetts). Among ART-conceived infants, 27.8% were low birthweight (range: 10.6% in Delaware to 44.4% in Puerto Rico), compared with 8.0% among all infants (range: 5.9% in Alaska to 11.3% in Mississippi). ART-conceived infants contributed to 4.7% of all preterm (<37 weeks) infants (range: 1.2% in Puerto Rico to 13.4% in Massachusetts). Percentages of preterm births were higher among infants conceived with ART (33.2%; range: 18.9% in the District of Columbia to 45.9% in Puerto Rico) than among all infants born in the total birth population (11.3%; range: 8.5% in California to 16.0% in Mississippi). The percentage of ART-conceived infants who were low birthweight was 8.9% (range: 3.2% in some states to 16.1% in Vermont) among singletons and 55.2% (range: 38.5% in Delaware to 77.8% in Alaska) among twins; the corresponding percentages of low birthweight infants among all infants born were 6.3% for singletons (range: 4.6% in Alaska, North Dakota, and Oregon to 9.5% in Puerto Rico) and 55.2% for twins (range: 46.1% in Alaska to 65.6% in Mississippi). The percentage of ART-conceived infants who were preterm was 13.2% (range: 7.5% in Rhode Island to 23.4% in West Virginia) among singletons and 62.2% (range: 33.3% in some states to 81.4% in Mississippi) among twins; the corresponding percentages of preterm infants among all infants were 9.7% for singletons (range: 1.7% in the District of Columbia to 14.2% in Mississippi) and 56.6% for twins (range: 47.2% in Vermont to 66.9% in Wyoming). Interpretation The percentage of infants conceived with ART varied considerably by reporting area. Multiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born. Low birthweight and preterm infant birth rates were disproportionately higher among ART-conceived infants than among the overall birth population. Although women aged <35 years are typically considered good candidates for eSET, on average two embryos were transferred per ART procedure with women in this group. Compared with ART-conceived singletons, ART-conceived twins were approximately five times more likely to be born preterm and approximately six times more likely to be born with low birthweight. Singleton infants conceived with ART had higher percentages of preterm birth and low birthweight than all singleton infants born in the United States. ART use per population unit was geographically variable, with 13 reporting areas showing ART use higher than the national rate. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive statewide-mandated health insurance coverage for ART procedures (i.e., coverage for at least four cycles of IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use exceeding 1.5 times the national rate. This type of mandated insurance has been associated with greater use of ART and likely accounts for some of the difference in per capita ART use observed among states. Public Health Action Reducing the number of embryos transferred and increasing use of eSET when clinically appropriate could help reduce multiple births and related adverse health consequences. Because twins account for the majority of ART-conceived multiple births, improved provider practices and patient education and counseling on the maternal and infant health risks of having twins are needed. Although ART contributes to high percentages of multiple births, other factors not investigated in this report (e.g., delayed childbearing and use of non-ART fertility treatments) also contribute to multiple births and warrant further study.

Levels of Neonatal Care

Provision of risk-appropriate care for newborn infants and mothers was first proposed in 1976. This updated policy statement provides a review of data supporting evidence for a tiered provision of care and reaffirms the need for uniform, nationally applicable definitions and consistent standards of service for public health to improve neonatal outcomes. Facilities that provide hospital care for newborn infants should be classified on the basis of functional capabilities, and these facilities should be organized within a regionalized system of perinatal care.

Severe obstetric morbidity in the United States: 1998-2005.

OBJECTIVE: To examine trends in the rates of severe obstetric complications and the potential contribution of changes in delivery mode and maternal characteristics to these trends. METHODS: We performed a cross-sectional study of severe obstetric complications identified from the 1998–2005 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. Logistic regression was used to examine the effect of changes in delivery mode and maternal characteristics on rates of severe obstetric complications. RESULTS: The prevalence of delivery hospitalizations (per 1,000) complicated by at least one severe obstetric complication increased from 0.64% (n=48,645) in 1998–1999 to 0.81% (n=68,433) in 2004–2005. Rates of complications that increased significantly during the study period included renal failure by 21% (from 0.23 to 0.28), pulmonary embolism by 52% (0.12 to 0.18), adult respiratory distress syndrome by 26% (0.36 to 0.45), shock by 24% (0.15 to 0.19), blood transfusion by 92% (2.38 to 4.58), and ventilation by 21 % (0.47 to 0.57). In logistic regression models, adjustment for maternal age had no effect on the increased risk for these complications in 2004–2005 relative to 1998–1999. However, after adjustment for mode of delivery, the increased risks for these complications in 2004–2005 relative to 1998–1999 were no longer significant, with the exception of pulmonary embolism (odds ratio 1.30) and blood transfusion (odds ratio 1.72). Further adjustment for payer, multiple births, and select comorbidities had little effect. CONCLUSION: Rates of severe obstetric complications increased from 1998–1999 to 2004–2005. For many of these complications, these increases were associated with the increasing rate of cesarean delivery. LEVEL OF EVIDENCE: III

Standard Terminology for Fetal, Infant, and Perinatal Deaths

Accurately defining and reporting perinatal deaths (ie, fetal and infant deaths) is a critical first step in understanding the magnitude and causes of these important events. In addition to obstetric health care providers, neonatologists and pediatricians should know the current US definitions and reporting requirements for live births, fetal deaths, and infant deaths. Correct identification of these vital events will improve our local, state, and national data so that these deaths can be better addressed and reduced.

Evaluating Loss to Follow-up in Newborn Hearing Screening in Massachusetts

OBJECTIVE. The purpose of this work was to examine loss to follow-up on the use of diagnostic or intervention services for Massachusetts infants and children screened or diagnosed with hearing loss and risk factors for becoming lost to follow-up. METHODS. We used data from the Massachusetts Childhood Hearing Data System and Early Intervention Information System. We calculated the percent use of audiologic evaluation for Massachusetts infants born in 2002–2003 who did not pass hearing screening and Early Intervention services for those with hearing loss. We generated crude and adjusted relative risks, as well as confidence intervals, to estimate associations of maternal and infant factors with the use of audiologic evaluation and early intervention services. Factors evaluated included childs birth weight and hearing screening or diagnostic results and maternal age, race or ethnicity, marital status, smoking status during pregnancy, educational attainment, health insurance, and residence region. RESULTS. In 2002–2003, 11% of Massachusetts children who did not pass hearing screening became lost to follow-up on the audiologic evaluation, and 25% of those with hearing loss did not receive early intervention services. Children were at higher risk of becoming lost to follow-up on audiologic evaluation if their mothers were nonwhite, covered by public insurance, smokers during pregnancy, or residing in western, northeastern, or southeastern Massachusetts compared with those in the Boston region. Of children with hearing loss, those with a unilateral or mild or moderate degree of hearing loss, normal birth weight, or living in the southeastern or Boston region were more likely to go without early intervention services. CONCLUSIONS. Massachusetts has excellent follow-up rates overall. Our analyses allow the program to prioritize limited resources to subgroups of infants who are at high risk of becoming lost to follow-up.

Maternal drug use and its effect on neonates: a population-based study in Washington State.

OBJECTIVE: To estimate the effect of maternal illicit and prescription drug use on neonates in Washington State between 2000 and 2008. METHODS: We used state-linked birth certificate and hospital discharge (mother and neonate) data to calculate prenatal drug exposure and neonatal abstinence syndrome rates, and compared state neonatal abstinence syndrome rates with national-level data from the Nationwide Inpatient Sample. We identified the drugs of exposure, examined predictors of drug exposure and neonatal abstinence syndrome, and assessed perinatal outcomes among drug-exposed and neonatal abstinence syndrome-diagnosed neonates compared with unexposed neonates. RESULTS: Drug exposure and neonatal abstinence syndrome rates increased significantly between 2000 and 2008, neonatal abstinence syndrome rates being consistently higher than national figures (3.3 compared with 2.8 per 1,000 births in 2008; P<.05). The proportion of neonatal abstinence syndrome-diagnosed neonates exposed prenatally to opioids increased from 26.4% in 2000 to 41.7% in 2008 (P<.05). Compared with unexposed neonates, drug-exposed and neonatal abstinence syndrome-diagnosed neonates had a lower mean birth weight, longer birth hospitalization, were more likely to be born preterm, experience feeding problems, and have respiratory conditions (all P<.001). CONCLUSION: Maternal use of illicit and prescription drugs was associated with considerable neonatal morbidity and significantly higher rates of drug exposure and neonatal abstinence syndrome in recent years. Data suggest that opioid analgesics contributed to the increase in prenatal drug exposure and neonatal abstinence syndrome in Washington State. In accordance with current guidelines, our findings emphasize the need for clinicians to screen pregnant women for illicit and prescription drug use and minimize use of opioid analgesics during pregnancy. LEVEL OF EVIDENCE: II

Birth outcomes of intended pregnancies among women who used assisted reproductive technology, ovulation stimulation, or no treatment

OBJECTIVE To study birth outcomes among live born infants conceived by women who used infertility treatment. DESIGN Population-based surveillance of women who recently delivered a live infant. SETTING The birth outcomes among infants whose mothers used assisted reproductive technology (ART) or ovulation stimulation medications alone were compared with the outcomes of infants conceived without treatment. PATIENT(S) Stratified random sample of women who were attempting conception and gave birth to a live infant in six US states (n = 16,748). INTERVENTION(S) Assisted reproductive technology and ovulation stimulation. MAIN OUTCOME MEASURE(S) Adjusted odds ratios for perinatal outcomes. RESULT(S) The prevalence of infertility treatment use overall among women attempting conception was 10.9% (5.4% ART procedures, 5.5% ovulation stimulation medications). Singletons of mothers who received ART procedures were more likely to be born with low birthweight, preterm, and small for gestational age (SGA) than singleton infants conceived without treatment. Singleton infants of mothers who used ovulation stimulation medications alone were more likely to be SGA than singleton infants conceived without treatment. No differences were found between ART and no treatment twin infants. CONCLUSION(S) Among singleton infants, ART is associated with decreased fetal growth, decreased gestational length, and SGA; ovulation stimulation alone is associated with SGA.

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.

Epidemiology and diagnosis of health care-associated infections in the NICU.

Health care−associated infections in the NICU are a major clinical problem resulting in increased morbidity and mortality, prolonged length of hospital stays, and increased medical costs. Neonates are at high risk for health care−associated infections because of impaired host defense mechanisms, limited amounts of protective endogenous flora on skin and mucosal surfaces at time of birth, reduced barrier function of neonatal skin, the use of invasive procedures and devices, and frequent exposure to broad-spectrum antibiotics. This statement will review the epidemiology and diagnosis of health care−associated infections in newborn infants.

Sickle Cell Disease and Pregnancy Outcomes: Women of African Descent

BACKGROUND Sickle cell disease (SCD) is a severe hematologic condition that presents unique complications among affected pregnant women. Many studies of adverse perinatal outcomes associated with SCD are limited by small samples or fail to consider important risk factors. PURPOSE This study compared perinatal outcomes among women of African ancestry with and without SCD in a large, population-based sample. METHODS Data from the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System were analyzed during June-August 2009 to identify in-state deliveries to resident women of African descent. Logistic regression analyses compared perinatal outcomes for deliveries among women with and without SCD, adjusted for maternal age, education, parity, plurality, insurance status, adequacy of prenatal care, smoking during pregnancy, and infant gender. RESULTS During 1998-2006, there were 116,076 deliveries to 84,561 women; SCD prevalence was 0.6%. Adjusted odds of fetal death among deliveries to women with SCD were 2.2 times those among women without SCD (95% CI=1.2, 4.2). Compared to women without SCD, the odds of preterm delivery, low birth weight, and having babies small for gestational age (SGA) among women with SCD were 1.5 (95% CI=1.2, 1.8); 1.7 (95% CI=1.1, 2.6); and 1.3 (95% CI=1.0, 1.7), respectively. Sickle cell disease was positively associated with cesarean delivery and inductions. CONCLUSIONS Population-based linked data systems are useful for assessing risks of adverse health outcomes among women with specific medical conditions, such as SCD. Women with SCD should seek preconception care to identify and modify risk behaviors and receive counseling regarding potential adverse sequelae associated with pregnancy-related morbidity and preterm delivery.