NHLBI/NICHD Collaborative Studies of Asthma in Pregnancy
Condition: Asthma; Lung Diseases
MeSH terms: Asthma; Lung Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      To conduct a collaborative program of research on asthma and pregnancy consisting of two
      studies: the Asthma in Pregnancy Study (APS) was an observational study to evaluate
      relationships between asthma severity and treatment programs and perinatal outcome, and the
      Asthma Therapy in Pregnancy Trial (ATPT) was a randomized clinical trial of inhaled
      beclomethasone versus theophylline in the treatment of moderate asthma during pregnancy. Both
      studies were conducted in the Maternal-Fetal Medicine Unit (MFMU) Network, an ongoing group
      of participating obstetric centers supported by the National Institute of Child Health and
      Human Development. Studies were co-funded by the NHLBI.
    

Detailed description: 
      BACKGROUND:

      Asthma is one of the most common illnesses that complicates pregnancy. Asthma complicates at
      least 4 percent of all pregnancies; however, because at least 10 percent of the population
      appears to have nonspecific airway hyper-responsiveness, the true prevalence may be much
      higher.

      Asthma can produce serious maternal and fetal complications. A number of investigators have
      reported an increased incidence of pre-eclampsia, gestational hypertension, hyperemesis
      gravidarum, vaginal hemorrhage, toxemia, and induced and complicated labor. Fetal
      complications include increased risk of perinatal mortality, prematurity, low birth weight,
      and neonatal hypoxia. In contrast, several studies have failed to confirm some or all of
      these previous observations. Patients with severe asthma may have the greatest risk for
      complications during pregnancy, in addition to the risk of maternal morbidity from the
      asthma. For example, it has been shown that reduced pulmonary function in asthmatic women is
      associated with an increased likelihood of intrauterine growth retardation. On the other
      hand, studies in which asthma was successfully controlled have resulted in pregnancy outcomes
      similar to the general population.

      The mechanisms by which asthma may have adverse perinatal effects are not well known. Poor
      control of asthma leading to chronic or episodic fetal hypoxia is thought to be important.
      Medications used in asthma treatment may also play a role, although the limited data suggests
      minimal or no effects. In addition, it is possible that extrapulmonary autonomic nervous
      system abnormalities, such as uterine muscle hyperreactivity, could contribute to pre-term
      delivery or gestational hypertension independent of asthma control or therapy.

      Unfortunately, previous studies have been limited by relatively small numbers. Few studies
      have controlled for factors known to affect infant birth weight, such as maternal race,
      height, weight, parity, nutrition, and cigarette smoking. Particularly, race may be an
      important contributing factor in assessing the relationship between asthma and pregnancy
      outcomes, since Blacks of both sexes are twice as likely to be hospitalized from asthma and
      three times as likely to die from asthma as whites.

      Under the auspices of the National Asthma Education Program (NAEP), a Working Group on Asthma
      and Pregnancy developed a statement regarding the treatment of asthma during pregnancy. In
      its deliberations, the Working Group noted the paucity of data on the relative contributions
      of biological, social, and environmental factors on asthma in pregnant women, as well as the
      lack of data on the efficacy and safety of commonly used asthma therapies in pregnancy.

      DESIGN NARRATIVE:

      The Asthma in Pregnancy Study evaluated the relationship between maternal asthma severity and
      control. The primary objective was to determine the frequency of preterm delivery <32 weeks
      among moderate and severe asthmatics compared to non-asthmatic controls. The incidence of
      small-for-gestational-age infants in women with mild and moderate asthma was a secondary
      outcome. Other independent variables included type of medications used, race, socioeconomic
      status, height, weight, parity, nutrition, smoking, other substance abuse, and prenatal care.
      Secondary outcomes included birth weight and prematurity, maternal pre-eclampsia, gestational
      hypertension, and asthma morbidity. The study began February 1,1995 and patient recruitment
      continued for 46 months or less.

      The Asthma Therapy in Pregnancy Trial was a randomized, double-blind, controlled clinical
      trial which began recruitment in November, 1996, with enrollment lasting 44 months. Patients
      were randomized to receive either active oral theophylline and a placebo beclomethasone
      inhaler or an active beclomethasone inhaler and placebo oral theophylline. Albuterol was used
      for relief of symptoms. The primary outcome measure was incidence of Emergency Department
      visits or hospitalizations during pregnancy. Secondary outcome measures included birth
      weight, incidence of small-for-gestational-age infants, gestational hypertension,
      pre-eclampsia, lung function, daily peak flow, and quality of life. Patients were seen
      monthly for measurements of fetal growth, morbidity, and lung function. Extensive interviews
      were conducted with each patient at the first prenatal visit, in the third trimester, and
      shortly before birth.

      The study completion date listed in this record was obtained from the "Completed Date"
      entered in the Query View Report System (QVR).
    

Intervention name(s): theophylline; beclomethasone
Intervention type(s): Drug; Drug
Intervention MeSH terms: Beclomethasone; Theophylline
Allocation: Randomized
Masking: Double
Primary purpose: Treatment