Table 6. Studies examining the long-term effects of prophylactic progesterone exposure in utero on childhood outcomes.

Author, year	Study population	Progesterone	Gestational age given	Delivery <34 weeks	Follow-up rate	Follow-up age	Congenital anomalies	Assessment tool 1 Progesterone vs. placebo	Assessment tool 2 Progesterone vs. placebo
Northen et al 2007 USA	Singletons (prior PTB)	Intramuscular 17 α-OHPC 250 mg/week	16–20 weeks to 36 weeks	RR 0.67 (0.48–0.93) #	80%	Mean 48 months	Genital / reproductive (2.1% vs. 1.2%; p = 1.0)	ASQ score below cut-off on at least one area (27.5% vs. 28%; p = 0.92)	PAI mean score (Boys: 66.5 vs. 67.3; p = 0.3. Girls: 32 vs. 33; p = 0.5)
Rode et al 2011 Austria/Denmark (PREDICT)	Twins	Vaginal natural progesterone 200 mg/day	20–24 weeks to 34 weeks	OR 0.80 (0.5–1.2)	79.2% and 74.8%*	6 months, 18 months	Congenital / chromosomal (3.8% vs. 4.0%; OR 1.0, 0.5–1.7)	ASQ mean score at 6 months of age (215 vs. 218; p = 0.45)	ASQ mean score at 18 months of age (193 vs. 194; p = 0.89)
McNamara et al 2015 United Kingdom (STOPPIT)	Twins	Vaginal natural progesterone 90 mg/day	24 to 34 weeks	OR 1.36 (0.89–2.09)	97% and 44%**	Mean 55 months	Congenital (4.0% vs. 4.0%; p = 0.92)	CDI score below cut-off on at least one area (30% vs. 35%; p = 0.66)	HUI global health rating‘Excellent’ (88% vs. 90%; p = 0.51)

PTB = preterm birth. 17 α -OHPC = 17 α -hydroxyprogesterone caproate. RR = relative risk (95% confidence interval). OR = odds ratio (95% confidence interval).

ASQ = Ages and Stages Questionnaire. PAI = Preschool Activities Inventory. CDI = Child Development Inventory. HUI = Health Utilities Index.

^#Delivery <35 weeks’ gestation.

*In the PREDICT study, follow-up was achieved for 79.2% of twins at 6 months of age and 74.8% of twins at 18 months of age.

**In our study, follow-up was achieved for 97% of twins via record linkage of at least one health record and 44% of twins via parental questionnaire.