see also:

• hyperemesis gravidarum
• Rh isoimmunisation and Anti-D prophylaxis
• PV bleeding in early pregnancy - miscarriage, ectopic pregnancy and more
  • miscarriage
  • ectopic pregnancy
  • molar pregnancy - hydatidiform mole, choriocarcinoma
  • foetal / fetal medicine
• PV bleeding in late pregnancy - abruption, placenta praevia and more
• trauma in the pregnant patient
• mid-trimester issues and complications
• pre-eclampsia and eclampsia
• labour
• prescribing in pregnancy - is the medicine safe?
• shortness of breath (SOB/dyspnoea) in pregnancy
• fetal radiation doses in pregnancy Xrays and CT scans
• ANZJOG 2023: The pregnant traveller: An overview of general travel advice (Pregnancy and travel risks)
• Australian Prescriber 2011 - analgesics in pregnancy and breastfeeding

• Maternal age and birth outcomes - New Jersey 1997

• maternal age 20-35 years
• paternal age 20-40 years
• socioeconomic factors
• adequate prenatal and antenatal care
• prenatal and antenatal folate supplements
• avoid prenatal antibiotics (other than penicillins and cephalosporins) where possible as seems these double risk of pregnancy loss in 1st 20wks¹⁾:
  • azithromycin, clarithromycin, tetracyclines, doxycycline, minocycline, quinolones, ciprofloxacin, norfloxacin, levofloxacin, sulfonamides and metronidazole
• avoid teratogenic exposures (radiation and medications) in 1st trimester (and in some cases such as Roaccutane, prenatally)
• avoid infections (rubella, varicella, toxoplasmosis, etc)
• avoid maternal lifestyle factors which may predispose to fertility or pregnancy outcome problems:
  • obesity
  • smoking
  • alcohol intake
  • substance abuse
  • sexually transmitted infections (STDs/STIs), in particular, pelvic inflammatory disease (PID)
  • very low weight
  • excessive exercise as this may impair ovulation and thus prevent fertility
  • avoid prenatal and antenatal potential toxins
    • prenatal bisphenol A (BPA) exposure significantly impacted aromatase activity in a male-specific manner in the mouse fetus, which subsequently led to anatomical, behavioral, and functional changes resembling autism. The study findings also suggest that the administration of 10-HDA has the potential to reverse these effects and ameliorate ASD symptoms.²⁾
• ensure adequate and timely medical intervention is available during labour
  • the planned home births system in WA has been associated with a 20x mortality!!! ³⁾

• aetiology:
  • oocyte/sperm defects - spontaneous mutations
  • uterine implantation ability - decreases with maternal age > 35yrs
  • placental blood flow - maternal pro-thrombotic disorders
  • immunologic
  • drug/chemical/viral damage
  • genetic causes
  • a small study in 2019 suggests high levels of insulin may be toxic to placental trophoblast cells and thus perhaps insulin resistance may have a role in miscarriages, metformin may be protective ⁴⁾
• risk of miscarriage:
  • maternal age:
    • risk of miscarriage requiring admission to hospital increases with maternal ages ~ exponentially after 25yrs:
      • < 25 yrs old: ~15% (9% if no prior aborts, ~20% if prior 1-2 aborts, 22% if prior > 2 aborts & parous, 50% if prior > 2 aborts & nulliparous)
      • 30 yrs old: ~ 18%
      • 35yrs old: ~23%
      • 40yrs old: ~35%
      • 45yrs old: ~60%
  • prior spontaneous abortions:
    • 1 abort: increases risk by ~ 40% (ie. 9% baseline risk for < 25yr old increases to ~12% risk)
    • 2 aborts: almost doubles risk (ie. 9% baseline risk for < 25yr old parous increases to ~17% risk but 23% if nulliparous)
    • > 2 aborts:
      • depends on whether nulliparous or not:
        • if nulliparous, risk increases to at least double baseline risk for age (eg. 50% for < 25yr olds, 40% for 30-40yr olds, 80% for 40-45yrolds)
        • if parous, increased risk is mainly to < 40yr olds (eg. 22% for < 25yr olds, 35% for 25-29yr olds, 32% for 30-39yr olds, 45% for 40-44 yr olds)
  • untreated coeliac disease is reported to have a 8-9x risk of recurrent miscarriages compared with treated patients but requires further study⁵⁾
  • working night shifts
    • 2 or more night shifts per week increases risk of miscarriage by 32% (Danish study 2019)

• incidence: 2.3% of all pregnancies admitted to hospital
• risks:
  • maternal age:
    • < 25yrs old: 1.4% risk
    • 25-30yrs: 2% risk
    • 35yrs: 4% risk
    • 40yrs: 6% risk
  • tubal damage:
    • pelvic inflammatory disease (PID)
    • tubal ligation
  • ciliary impairment - smoking, progesterone only pills
  • ovulation induction

• see stillbirths

• hydatidiform mole
• Down's syndrome:
  • maternal age
• achondroplasia:
  • paternal age
• schizophrenia:
  • paternal age - age > 50yrs 2x risk
• autism:
  • paternal age - age > 50yrs 2x risk

• maternal folate status
• maternal age

• severely teratogenic agents such as:
  • isotretinoin (Roaccutane)
• fetal alcohol syndrome
• many others

• TORCH
  • toxoplasmosis
  • Other infections: syphilis, varicella-zoster, parvovirus B19, zika virus
  • Rubella
  • Cytomegalovirus (CMV)
  • Herpes infections

• survival rates (RWH, Victoria, 2005):
  • < 23wks: rare - smallest surviving baby at RWH weighed 374g
  • 23wks: 67% (40% in 1997)
  • 24-25wks: 77% (73% in 1997)
  • 26-27wks: 82% with 1 in 5 having serious disability ?
  • 28-32wks: 98%   
  • term: 99% with 1 in 25 having serious disability
• cutoff gestation for ICU care (costs $A2740 per day in 2005):
  • Holland 2005: 25-26wks or less
  • UK: under consideration by ethics committees 
  • Aust: no official cutoff but very unlikely a 22wk would get ICU care

• overall risk of having a child with congenital anomalies is still relatively low, their fetuses may be predisposed to certain defects
• gastroschisis
• patent ductus arteriosis
• pyloric stenosis
• spina bifida
• hydranecephaly
• septo-optic dysplasia
• optic nerve hypoplasia
• anencephaly
• cleft lip
• polydactyly
• schizencephaly

• fertility declines with age:
  • one-third of women aged 35-39 and 50% of those over age 40 have fertility problems.
• the incidence of pregnancy complications increases with maternal age:
  • hypertension
  • diabetes
  • premature births
  • stillbirths (overall risk not relative risk):
    • < 20 yrs: 0.5% risk
    • 20-30yrs: 0.4% risk
    • 35-39yrs: 0.5% risk
    • 40-44yrs: 0.65% risk
    • > 44yrs: 0.8% risk
  • twin pregnancy
• the incidence of miscarriage increases:
  • < 25 yrs old: ~15% (9% if no prior aborts, ~20% if prior 1-2 aborts, 22% if prior > 2 aborts & parous, 50% if prior > 2 aborts & nulliparous)
  • 30 yrs old: ~ 18%
  • 35yrs old: ~23%
  • 40yrs old: ~35%
  • 45yrs old: ~60%
• the incidence of birth defects increases with maternal age > 35 years:
  • trisomy 21 (Down's syndrome)
    • age 25 risk 1 in 1,250
    • age 30 risk 1 in 1,000
    • age 35 risk 1 in 400
    • age 40 risk 1 in 100
    • age 45 risk 1 in 30
  • congenital heart disease⁶⁾:
    • laterality defects 2x risk
    • all conotruncal defects 1.3x risk
      • dextro-transposition of the great arteries 1.65x risk
      • coarctation of the aorta 1.5x risk
      • ventricular septal defects 1.2x risk
      • atrial septal defects 1.4x risk

• 1.1 x risk for low birthweight
• increased neonatal and infant deaths
• lower IQ

• it is believed that DNA from the sperm cells of older fathers are more likely to develop CNVs than that from younger fathers.
  • CNVs are specific DNA mutations in which whole “chapters” of genetic material are either deleted or repeated.
• age > 50 yrs doubles risk of autism and schizophrenia
  • paternal age appears to account for at least 25% of all schizophrenia
• miscarriage rates
• possibly decreased fertility
• increased stillbirths
• perhaps increased pre-eclampsia
• 1.2x risk for low birth weight
• bipolar depression
• 1.09 x risk for each 10 year increment in paternal age for development of childhood brain cancer
• lower IQ if age > 44
• 2-3x higher childhood mortality

• Maternal age & fetal loss. Nybo Andersen et al. BMJ 2000; 320: 1708-12; (Denmark - 634272 women 1978-1992)